ijms-logo

Journal Browser

Journal Browser

Special Issue "Molecular Machinery of Cell Growth Regulation"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 September 2015).

Special Issue Editor

Prof. Dr. Alan C. Leonard
E-Mail Website
Guest Editor
Department of Biological Sciences, Florida Institute of Technology, Melbourne, FL, USA
Interests: cell cycle; initiation of chromosome replication; DNA-protein interactions; bacterial growth and division

Special Issue Information

Dear Colleagues,

The reproduction of cells requires the coordinated regulation of many events, including the accumulation of mass, genome duplication, segregation of newly synthesized chromosomes into daughter cells, and finally, cell division. A variety of different complex molecular machines ensure that each stage of the cell cycle is properly ordered and precisely timed, with malfunctions leading to either cell death or cancer. Although dissection of these regulators remains a daunting task, significant progress has come from studies in a variety of organisms, and with a diverse range of experimental approaches. These approaches are now highly interdisciplinary and include high-resolution microscopy, nuclear magnetic resonance spectroscopy, X-ray crystallography, and single-molecule methods, as well as genetic and biochemical studies. We cordially invite you to contribute papers that further our understanding of growth regulation in normal cells, or in cells that no longer properly regulate their reproduction.

Alan C. Leonard
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • cell cycle
  • cell growth
  • chromosome replication
  • mitosis
  • chromosome segregation
  • protein synthesis
  • cell division
  • cell size
  • cell signaling
  • nucleoprotein complexes

Published Papers (21 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals
Int. J. Mol. Sci. 2016, 17(1), 37; https://doi.org/10.3390/ijms17010037 - 28 Dec 2015
Cited by 15 | Viewed by 3142
Abstract
Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment [...] Read more.
Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
DNA Double Strand Break Response and Limited Repair Capacity in Mouse Elongated Spermatids
Int. J. Mol. Sci. 2015, 16(12), 29923-29935; https://doi.org/10.3390/ijms161226214 - 16 Dec 2015
Cited by 14 | Viewed by 3182
Abstract
Spermatids are extremely sensitive to genotoxic exposures since during spermiogenesis only error-prone non homologous end joining (NHEJ) repair pathways are available. Hence, genomic damage may accumulate in sperm and be transmitted to the zygote. Indirect, delayed DNA fragmentation and lesions associated with apoptotic-like [...] Read more.
Spermatids are extremely sensitive to genotoxic exposures since during spermiogenesis only error-prone non homologous end joining (NHEJ) repair pathways are available. Hence, genomic damage may accumulate in sperm and be transmitted to the zygote. Indirect, delayed DNA fragmentation and lesions associated with apoptotic-like processes have been observed during spermatid elongation, 27 days after irradiation. The proliferating spermatogonia and early meiotic prophase cells have been suggested to retain a memory of a radiation insult leading later to this delayed fragmentation. Here, we used meiotic spread preparations to localize phosphorylate histone H2 variant (γ-H2AX) foci marking DNA double strand breaks (DSBs) in elongated spermatids. This technique enabled us to determine the background level of DSB foci in elongated spermatids of RAD54/RAD54B double knockout (dko) mice, severe combined immunodeficiency SCID mice, and poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP1) inhibitor (DPQ)-treated mice to compare them with the appropriate wild type controls. The repair kinetics data and the protein expression patterns observed indicate that the conventional NHEJ repair pathway is not available for elongated spermatids to repair the programmed and the IR-induced DSBs, reflecting the limited repair capacity of these cells. However, although elongated spermatids express the proteins of the alternative NHEJ, PARP1-inhibition had no effect on the repair kinetics after IR, suggesting that DNA damage may be passed onto sperm. Finally, our genetic mutant analysis suggests that an incomplete or defective meiotic recombinational repair of Spo11-induced DSBs may lead to a carry-over of the DSB damage or induce a delayed nuclear fragmentation during the sensitive programmed chromatin remodeling occurring in elongated spermatids. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessArticle
Protein Arginine Methyltransferase 6 Involved in Germ Cell Viability during Spermatogenesis and Down-Regulated by the Androgen Receptor
Int. J. Mol. Sci. 2015, 16(12), 29467-29481; https://doi.org/10.3390/ijms161226186 - 10 Dec 2015
Cited by 6 | Viewed by 2527
Abstract
Androgens and the androgen receptor (AR) are of great importance to spermatogenesis and male fertility. AR knockout (ARKO) mice display a complete insensitivity to androgens and male infertility; however, the exact molecular mechanism for this effect remains unclear. In this study, we found [...] Read more.
Androgens and the androgen receptor (AR) are of great importance to spermatogenesis and male fertility. AR knockout (ARKO) mice display a complete insensitivity to androgens and male infertility; however, the exact molecular mechanism for this effect remains unclear. In this study, we found that the expression levels of Prmt6 mRNA and protein were significantly up-regulated in the testes of ARKO mice compared to wild type (WT) mice. PRMT6 was principally localized to the nucleus of spermatogonia and spermatocytes by immunofluorescence staining. Furthermore, luciferase assay data showed that AR together with testosterone treatment suppressed Prmt6 transcription via binding to the androgen-responsive element (ARE) of the Prmt6 promoter. Moreover, knockdown of Prmt6 suppressed germ cells migration and promoted apoptosis. In addition, both of these cellular activities could not be enhanced by testosterone treatment. Taken together, these data indicate that PRMT6, which was down-regulated by AR and influenced cell migration and apoptosis of germ cells, could play a potentially important role in spermatogenesis. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessArticle
ADP-Ribosylation Factor 1 Regulates Proliferation, Migration, and Fusion in Early Stage of Osteoclast Differentiation
Int. J. Mol. Sci. 2015, 16(12), 29305-29314; https://doi.org/10.3390/ijms161226168 - 09 Dec 2015
Cited by 4 | Viewed by 2857
Abstract
Small G-protein adenosine diphosphate (ADP)-ribosylation factors (ARFs) regulate a variety of cellular functions, including actin cytoskeleton remodeling, plasma membrane reorganization, and vesicular transport. Here, we propose the functional roles of ARF1 in multiple stages of osteoclast differentiation. ARF1 was upregulated during receptor activator [...] Read more.
Small G-protein adenosine diphosphate (ADP)-ribosylation factors (ARFs) regulate a variety of cellular functions, including actin cytoskeleton remodeling, plasma membrane reorganization, and vesicular transport. Here, we propose the functional roles of ARF1 in multiple stages of osteoclast differentiation. ARF1 was upregulated during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and transiently activated in an initial stage of their differentiation. Differentiation of ARF1-deficient osteoclast precursors into mature osteoclasts temporarily increased in pre-maturation stage of osteoclasts followed by reduced formation of mature osteoclasts, indicating that ARF1 regulates the osteoclastogenic process. ARF1 deficiency resulted in reduced osteoclast precursor proliferation and migration as well as increasing cell-cell fusion. In addition, ARF1 silencing downregulated c-Jun N-terminal kinase (JNK), Akt, osteopontin, and macrophage colony-stimulating factor (M-CSF)-receptor c-Fms as well as upregulating several fusion-related genes including CD44, CD47, E-cadherin, and meltrin-α. Collectively, we showed that ARF1 stimulated proliferation and migration of osteoclast precursors while suppressing their fusion, suggesting that ARF1 may be a plausible inter-player that mediates the transition to osteoclast fusion at multiple steps during osteoclast differentiation Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
Accumulation and Phosphorylation of RecQ-Mediated Genome Instability Protein 1 (RMI1) at Serine 284 and Serine 292 during Mitosis
Int. J. Mol. Sci. 2015, 16(11), 26395-26405; https://doi.org/10.3390/ijms161125965 - 04 Nov 2015
Cited by 4 | Viewed by 2642
Abstract
Chromosome instability usually leads to tumorigenesis. Bloom syndrome (BS) is a genetic disease associated with chromosome instability. The BS gene product, BLM, has been reported to function in the spindle assembly checkpoint (SAC) to prevent chromosome instability. BTR complex, composed of BLM, topoisomerase [...] Read more.
Chromosome instability usually leads to tumorigenesis. Bloom syndrome (BS) is a genetic disease associated with chromosome instability. The BS gene product, BLM, has been reported to function in the spindle assembly checkpoint (SAC) to prevent chromosome instability. BTR complex, composed of BLM, topoisomerase IIIα (Topo IIIα), RMI1 (RecQ-mediated genome instability protein 1, BLAP75) and RMI2 (RecQ-mediated genome instability protein 2, BLAP18), is crucial for maintaining genome stability. Recent work has demonstrated that RMI2 also plays critical role in SAC. However, little is know about RMI1 regulation during the cell cycle. Here we present that RMI1 protein level does not change through G1, S and G2 phases, but significantly increases in M phase. Moreover, phosphorylation of RMI1 occurs in mitosis. Upon microtubule-disturbing agent, RMI1 is phosphorylated primarily at the sites of Serine 284 and Serine 292, which does not interfere with the formation of BTR complex. Additionally, this phosphorylation is partially reversed by roscovitine treatment, implying cycling-dependent kinase 1 (CDK1) might be one of the upstream kinases. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessArticle
Myomaker, Regulated by MYOD, MYOG and miR-140-3p, Promotes Chicken Myoblast Fusion
Int. J. Mol. Sci. 2015, 16(11), 26186-26201; https://doi.org/10.3390/ijms161125946 - 02 Nov 2015
Cited by 49 | Viewed by 3689
Abstract
The fusion of myoblasts is an important step during skeletal muscle differentiation. A recent study in mice found that a transmembrane protein called Myomaker, which is specifically expressed in muscle, is critical for myoblast fusion. However, the cellular mechanism of its roles and [...] Read more.
The fusion of myoblasts is an important step during skeletal muscle differentiation. A recent study in mice found that a transmembrane protein called Myomaker, which is specifically expressed in muscle, is critical for myoblast fusion. However, the cellular mechanism of its roles and the regulatory mechanism of its expression remain unclear. Chicken not only plays an important role in meat production but is also an ideal model organism for muscle development research. Here, we report that Myomaker is also essential for chicken myoblast fusion. Forced expression of Myomaker in chicken primary myoblasts promotes myoblast fusion, whereas knockdown of Myomaker by siRNA inhibits myoblast fusion. MYOD and MYOG, which belong to the family of myogenic regulatory factors, can bind to a conserved E-box located proximal to the Myomaker transcription start site and induce Myomaker transcription. Additionally, miR-140-3p can inhibit Myomaker expression and myoblast fusion, at least in part, by binding to the 3ʹ UTR of Myomaker in vitro. These findings confirm the essential roles of Myomaker in avian myoblast fusion and show that MYOD, MYOG and miR-140-3p can regulate Myomaker expression. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma
Int. J. Mol. Sci. 2015, 16(10), 24574-24587; https://doi.org/10.3390/ijms161024574 - 15 Oct 2015
Cited by 35 | Viewed by 2884
Abstract
Accumulating evidence shows that activity of the pyruvate kinase M2 (PKM2) isoform is closely related to tumorigenesis. In this study, we investigated the relationship betweenPKM2 expression, tumor invasion, and the prognosis of patients with lung adenocarcinoma. We retrospectively analyzed 65 cases of [...] Read more.
Accumulating evidence shows that activity of the pyruvate kinase M2 (PKM2) isoform is closely related to tumorigenesis. In this study, we investigated the relationship betweenPKM2 expression, tumor invasion, and the prognosis of patients with lung adenocarcinoma. We retrospectively analyzed 65 cases of patients with lung adenocarcinoma who were divided into low and a high expression groups based on PKM2immunohistochemical staining. High PKM2 expression was significantly associated with reduced patient survival. We used small interfering RNA (siRNA) technology to investigate the effect of targeted PKM2-knockout on tumor growth at the cellular level. In vitro, siRNA-mediated PKM2-knockdown significantly inhibited the proliferation, glucose uptake (25%), ATP generation (20%) and fatty acid synthesis of A549 cells, while the mitochondrial respiratory capacity of the cells increased (13%).Western blotting analysis showed that PKM2-knockout significantly inhibited the expression of the glucose transporter GLUT1 and ATP citrate lyase, which is critical for fatty acid synthesis. Further Western blotting analysis showed that PKM2-knockdown inhibited the expression of matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF), which are important in degradation of the extracellular matrix and angiogenesis, respectively. These observations show that PKM2 activates both glycolysis and lipid synthesis, thereby regulating cell proliferation and invasion. This information is important in elucidating the mechanisms by which PKM2 influences the growth and metastasis of lung adenocarcinoma at the cellular and molecular level, thereby providing the basic data required for the development of PKM2-targeted gene therapy. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessArticle
Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDHInhibits Cell Growth and Induces Apoptosis by Regulatingthe PTEN/AKT Pathway in Hepatocellular Carcinoma
Int. J. Mol. Sci. 2015, 16(8), 19419-19432; https://doi.org/10.3390/ijms160819419 - 17 Aug 2015
Cited by 26 | Viewed by 2754
Abstract
The activation of oncogenes and the loss of tumor suppressor genes are believed toplay critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin (MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles [...] Read more.
The activation of oncogenes and the loss of tumor suppressor genes are believed toplay critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin (MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles of MTDH with regard to growth and apoptosis in HCC have not yet been studied. In the present study, we first analyzed the expression of MTDH in HCC samples. We found that MTDH protein levels are higher in most HCC cancerous tissues compared with their matched adjacent non-tumor tissues. Additionally, the MTDH mRNA was also higher in HCC tissues compared to their matched adjacent non-tumor tissues. Knockdown of the endogenous MTDH using small interfering RNA further showed that deficiency of MTDH suppressed cell growth and caused apoptosis in HCC cells. Knockdown MTDH promoted PTEN and p53 expression in HCC cells and inhibited AKT phosphorylation. Knockdown MTDH also inhibited tumor growth in vivo. All these results indicated that MTDH protein levels in most HCC tissues are higher than non-tumor tissues, and knockdown of MTDH inhibited growth and induced apoptosis in HCC cells through the activation of PTEN. Therefore, MTDH might be an effective targeted therapy gene for HCC. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessArticle
Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest
Int. J. Mol. Sci. 2015, 16(8), 19401-19418; https://doi.org/10.3390/ijms160819401 - 17 Aug 2015
Cited by 5 | Viewed by 3193
Abstract
The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate [...] Read more.
The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessArticle
Polymodal Transient Receptor Potential Vanilloid (TRPV) Ion Channels in Chondrogenic Cells
Int. J. Mol. Sci. 2015, 16(8), 18412-18438; https://doi.org/10.3390/ijms160818412 - 07 Aug 2015
Cited by 22 | Viewed by 4380
Abstract
Mature and developing chondrocytes exist in a microenvironment where mechanical load, changes of temperature, osmolarity and acidic pH may influence cellular metabolism. Polymodal Transient Receptor Potential Vanilloid (TRPV) receptors are environmental sensors mediating responses through activation of linked intracellular signalling pathways. In chondrogenic [...] Read more.
Mature and developing chondrocytes exist in a microenvironment where mechanical load, changes of temperature, osmolarity and acidic pH may influence cellular metabolism. Polymodal Transient Receptor Potential Vanilloid (TRPV) receptors are environmental sensors mediating responses through activation of linked intracellular signalling pathways. In chondrogenic high density cultures established from limb buds of chicken and mouse embryos, we identified TRPV1, TRPV2, TRPV3, TRPV4 and TRPV6 mRNA expression with RT-PCR. In both cultures, a switch in the expression pattern of TRPVs was observed during cartilage formation. The inhibition of TRPVs with the non-selective calcium channel blocker ruthenium red diminished chondrogenesis and caused significant inhibition of proliferation. Incubating cell cultures at 41 °C elevated the expression of TRPV1, and increased cartilage matrix production. When chondrogenic cells were exposed to mechanical load at the time of their differentiation into matrix producing chondrocytes, we detected increased mRNA levels of TRPV3. Our results demonstrate that developing chondrocytes express a full palette of TRPV channels and the switch in the expression pattern suggests differentiation stage-dependent roles of TRPVs during cartilage formation. As TRPV1 and TRPV3 expression was altered by thermal and mechanical stimuli, respectively, these are candidate channels that contribute to the transduction of environmental stimuli in chondrogenic cells. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
BAMBI Promotes C2C12 Myogenic Differentiation by Enhancing Wnt/β-Catenin Signaling
Int. J. Mol. Sci. 2015, 16(8), 17734-17745; https://doi.org/10.3390/ijms160817734 - 03 Aug 2015
Cited by 19 | Viewed by 3807
Abstract
Bone morphogenic protein and activin membrane-bound inhibitor (BAMBI) is regarded as an essential regulator of cell proliferation and differentiation that represses transforming growth factor-β and enhances Wnt/β-catenin signaling in various cell types. However, its role in skeletal muscle remains largely unknown. [...] Read more.
Bone morphogenic protein and activin membrane-bound inhibitor (BAMBI) is regarded as an essential regulator of cell proliferation and differentiation that represses transforming growth factor-β and enhances Wnt/β-catenin signaling in various cell types. However, its role in skeletal muscle remains largely unknown. In the current study, we found that the expression level of BAMBI peaked in the early differentiation phase of the C2C12 rodent myoblast cell line. Knockdown of BAMBI via siRNA inhibited C2C12 differentiation, indicated by repressed MyoD, MyoG, and MyHC expression as well as reductions in the differentiation and fusion indices. BAMBI knockdown reduced the activity of Wnt/β-catenin signaling, as characterized by the decreased nuclear translocation of β-catenin and the lowered transcription of Axin2, which is a well-documented target gene of the Wnt/β-catenin signaling pathway. Furthermore, treatment with LiCl, an activator of Wnt/β-catenin signaling, rescued the reduction in C2C12 differentiation caused by BAMBI siRNA. Taken together, our data suggest that BAMBI is required for normal C2C12 differentiation, and that its role in myogenesis is mediated by the Wnt/β-catenin pathway. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessArticle
Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures
Int. J. Mol. Sci. 2015, 16(8), 17344-17367; https://doi.org/10.3390/ijms160817344 - 29 Jul 2015
Cited by 15 | Viewed by 3150
Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no [...] Read more.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no data can be found if PACAP signaling is playing any role during mechanical stress in any tissues, we aimed to investigate its contribution in mechanotransduction during chondrogenesis. Expressions of the mRNAs of PACAP and its major receptor, PAC1 increased, while that of other receptors, VPAC1, VPAC2 decreased upon mechanical stimulus. Mechanical load enhanced the expression of collagen type X, a marker of hypertrophic differentiation of chondrocytes and PACAP addition attenuated this elevation. Moreover, exogenous PACAP also prevented the mechanical load evoked activation of hedgehog signaling: protein levels of Sonic and Indian Hedgehogs and Gli1 transcription factor were lowered while expressions of Gli2 and Gli3 were elevated by PACAP application during mechanical load. Our results suggest that mechanical load activates PACAP signaling and exogenous PACAP acts against the hypertrophy inducing effect of mechanical load. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
miR-198 Represses the Proliferation of HaCaT Cells by Targeting Cyclin D2
Int. J. Mol. Sci. 2015, 16(8), 17018-17028; https://doi.org/10.3390/ijms160817018 - 27 Jul 2015
Cited by 13 | Viewed by 2829
Abstract
Background: MiR-198 has been considered as an inhibitor of cell proliferation, invasion, migration and a promoter of apoptosis in most cancer cells, while its effect on non-cancer cells is poorly understood. Methods: The effect of miR-198 transfection on HaCaT cell proliferation was firstly [...] Read more.
Background: MiR-198 has been considered as an inhibitor of cell proliferation, invasion, migration and a promoter of apoptosis in most cancer cells, while its effect on non-cancer cells is poorly understood. Methods: The effect of miR-198 transfection on HaCaT cell proliferation was firstly detected using Cell Count Kit-8 and the cell cycle progression was analyzed by flow cytometry. Using bioinformatics analyses and luciferase assay, a new target of miR-198 was searched and identified. Then, the effect of the new target gene of miR-198 on cell proliferation and cell cycle was also detected. Results: Here we showed that miR-198 directly bound to the 3′-UTR of CCND2 mRNA, which was a key regulator in cell cycle progression. Overexpressed miR-198 repressed CCND2 expression at mRNA and protein levels and subsequently led to cell proliferation inhibition and cell cycle arrest in the G1 phase. Transfection ofSiCCND2 in HaCaT cells showed similar inhibitory effects on cell proliferation and cell cycle progression. Conclusion: In conclusion, we have identified that miR-198 inhibited HaCaT cell proliferation by directly targeting CCND2. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
Deep Sequencing Analysis of miRNA Expression in Breast Muscle of Fast-Growing and Slow-Growing Broilers
Int. J. Mol. Sci. 2015, 16(7), 16242-16262; https://doi.org/10.3390/ijms160716242 - 17 Jul 2015
Cited by 28 | Viewed by 3171
Abstract
Growth performance is an important economic trait in chicken. MicroRNAs (miRNAs) have been shown to play important roles in various biological processes, but their functions in chicken growth are not yet clear. To investigate the function of miRNAs in chicken growth, breast muscle [...] Read more.
Growth performance is an important economic trait in chicken. MicroRNAs (miRNAs) have been shown to play important roles in various biological processes, but their functions in chicken growth are not yet clear. To investigate the function of miRNAs in chicken growth, breast muscle tissues of the two-tail samples (highest and lowest body weight) from Recessive White Rock (WRR) and Xinghua Chickens (XH) were performed on high throughput small RNA deep sequencing. In this study, a total of 921 miRNAs were identified, including 733 known mature miRNAs and 188 novel miRNAs. There were 200, 279, 257 and 297 differentially expressed miRNAs in the comparisons of WRRh vs. WRRl, WRRh vs. XHh, WRRl vs. XHl, and XHh vs. XHl group, respectively. A total of 22 highly differentially expressed miRNAs (fold change > 2 or < 0.5; p-value < 0.05; q-value < 0.01), which also have abundant expression (read counts > 1000) were found in our comparisons. As far as two analyses (WRRh vs. WRRl, and XHh vs. XHl) are concerned, we found 80 common differentially expressed miRNAs, while 110 miRNAs were found in WRRh vs. XHh and WRRl vs. XHl. Furthermore, 26 common miRNAs were identified among all four comparisons. Four differentially expressed miRNAs (miR-223, miR-16, miR-205a and miR-222b-5p) were validated by quantitative real-time RT-PCR (qRT-PCR). Regulatory networks of interactions among miRNAs and their targets were constructed using integrative miRNA target-prediction and network-analysis. Growth hormone receptor (GHR) was confirmed as a target of miR-146b-3p by dual-luciferase assay and qPCR, indicating that miR-34c, miR-223, miR-146b-3p, miR-21 and miR-205a are key growth-related target genes in the network. These miRNAs are proposed as candidate miRNAs for future studies concerning miRNA-target function on regulation of chicken growth. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
Effect of Melatonin on the Extracellular-Regulated Kinase Signal Pathway Activation and Human Osteoblastic Cell Line hFOB 1.19 Proliferation
Int. J. Mol. Sci. 2015, 16(5), 10337-10353; https://doi.org/10.3390/ijms160510337 - 07 May 2015
Cited by 14 | Viewed by 2621
Abstract
It has been shown that melatonin may affect bone metabolism. However, it is controversial whether melatonin could promote osteoblast proliferation, and the precise molecular mechanism of melatonin on osteoblast proliferation is still obscure. In this study, the results of the CCK-8 assay showed [...] Read more.
It has been shown that melatonin may affect bone metabolism. However, it is controversial whether melatonin could promote osteoblast proliferation, and the precise molecular mechanism of melatonin on osteoblast proliferation is still obscure. In this study, the results of the CCK-8 assay showed that melatonin significantly promoted human osteoblastic cell line hFOB 1.19 cell proliferation at 1, 2.5, 5, 10, 25, 50 and 100 µM concentrations for 24 h, but there were no significant differences among the groups. Western blot demonstrated that 10 µM melatonin significantly promoted ERK1/2 phosphorylation. Furthermore, we also detected the phosphorylation of c-Raf, MEK1/2, p90RSK and MSK1, and all of them increased with 10 µM melatonin. U0126 (a selective inhibitor of MEK that disrupts downstream activation of ERK1/2) downregulated the phosphorylation of ERK1/2, p90RSK and MSK1. U0126 also attenuated the proliferation of osteoblasts stimulated by melatonin. In conclusion, this study for the first time indicates that melatonin (10 nM–100 µM) promotes the proliferation of a human osteoblastic cell line hFOB 1.19 through activation of c-Raf, MEK1/2, ERK1/2, p90RSK and MSK1. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessCommunication
Identification of an AMPK Phosphorylation Site in Drosophila TSC2 (gigas) that Regulate Cell Growth
Int. J. Mol. Sci. 2015, 16(4), 7015-7026; https://doi.org/10.3390/ijms16047015 - 27 Mar 2015
Cited by 14 | Viewed by 3705
Abstract
AMP-activated protein kinase (AMPK) is an important metabolic regulator that mediates cellular adaptation to diverse stresses. One of the AMPK substrates, tuberous sclerosis complex 2 (TSC2), was suggested to mediate AMPK-induced silencing of mTOR complex 1 (mTORC1) signaling that is critical for cell [...] Read more.
AMP-activated protein kinase (AMPK) is an important metabolic regulator that mediates cellular adaptation to diverse stresses. One of the AMPK substrates, tuberous sclerosis complex 2 (TSC2), was suggested to mediate AMPK-induced silencing of mTOR complex 1 (mTORC1) signaling that is critical for cell growth. However, it is not known whether the AMPK-dependent TSC2 phosphorylation, originally observed in mammalian cells, is conserved in invertebrates. Here we show that energy depletion inhibits mTORC1 signaling through the AMPK-TSC2 axis in Drosophila S2 cells. We have discovered an AMPK phosphorylation site in TSC2-like genes from many different invertebrate species including Drosophila. The site (Ser1338 in Drosophila TSC2) is specifically and efficiently phosphorylated by AMPK in vitro. To evaluate the functional role of this phosphorylation site in vivo, we generated transgenic flies that can express identical amount of either wild-type or phosphorylation-resistant mutant Drosophila TSC2 in a tissue-specific manner. In response to transgenic Sestrin induction, which causes ectopic AMPK activation and subsequent mTORC1 inhibition, wild-type Drosophila TSC2 synergistically reduced tissue growth in the dorsal epithelium of Drosophila wings. However, phosphorylation-resistant mutant Drosophila TSC2 was unable to show such a growth-inhibiting effect, suggesting that this phosphorylation is important for AMPK-dependent regulation of cell growth. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessArticle
Depletion of C3orf1/TIMMDC1 Inhibits Migration and Proliferation in 95D Lung Carcinoma Cells
Int. J. Mol. Sci. 2014, 15(11), 20555-20571; https://doi.org/10.3390/ijms151120555 - 10 Nov 2014
Cited by 6 | Viewed by 2846
Abstract
In our previous study, we identified an association of high expression of c3orf1, also known as TIMMDC1 (translocase of inner mitochondrial membrane domain-containing protein 1), with metastatic characteristics in lung carcinoma cells. To investigate the preliminary function and mechanism of this mitochondrial [...] Read more.
In our previous study, we identified an association of high expression of c3orf1, also known as TIMMDC1 (translocase of inner mitochondrial membrane domain-containing protein 1), with metastatic characteristics in lung carcinoma cells. To investigate the preliminary function and mechanism of this mitochondrial protein, we depleted C3orf1 expression by introducing siRNA into 95D lung carcinoma cells. We demonstrated that C3orf1 depletion significantly suppressed 95D cell growth and migration. We confirmed C3orf1 localization in the inner mitochondrial membrane and showed that mitochondrial viability, membrane potential, and ATPase activity were remarkably reduced upon depletion of C3orf1. Microarray data indicated that genes involved in regulation of cell death, migration, and cell-cycle arrest were significantly altered after C3orf1 depletion for 48 h. The expression of genes involved in focal adhesion, ECM-receptor interaction, and p53-signaling pathways were notably altered. Furthermore, cell-cycle arrest genes such as CCNG2 and PTEN as well as genes involved in cell migration inhibition, such as TIMP3 and COL3A1, were upregulated after C3orf1 depletion in 95D cells. Concurrently, expression of the migration-promoting gene NUPR1 was markedly reduced, as confirmed by real-time PCR. We conclude that C3orf1 is critical for mitochondrial function, migration, and proliferation in 95D lung carcinoma cells. Depletion of C3orf1 inhibited cell migration and cell proliferation in association with upregulation of genes involved in cell-cycle arrest and cell migration inhibition. These results suggest that C3orf1 (TIMMDC1) may be a viable treatment target for lung carcinoma, and that further study of the role of this protein in lung carcinoma pathogenesis is justified. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
The Role of Cdkn1A-Interacting Zinc Finger Protein 1 (CIZ1) in DNA Replication and Pathophysiology
Int. J. Mol. Sci. 2016, 17(2), 212; https://doi.org/10.3390/ijms17020212 - 05 Feb 2016
Cited by 8 | Viewed by 3115
Abstract
Cdkn1A-interacting zinc finger protein 1 (CIZ1) was first identified in a yeast-2-hybrid system searching for interacting proteins of CDK2 inhibitor p21Cip1/Waf1. Ciz1 also binds to CDK2, cyclin A, cyclin E, CDC6, PCNA, TCF4 and estrogen receptor-α. Recent studies reveal numerous biological [...] Read more.
Cdkn1A-interacting zinc finger protein 1 (CIZ1) was first identified in a yeast-2-hybrid system searching for interacting proteins of CDK2 inhibitor p21Cip1/Waf1. Ciz1 also binds to CDK2, cyclin A, cyclin E, CDC6, PCNA, TCF4 and estrogen receptor-α. Recent studies reveal numerous biological functions of CIZ1 in DNA replication, cell proliferation, and differentiation. In addition, splicing variants of CIZ1 mRNA is associated with a variety of cancers and Alzheimer’s disease, and mutations of the CIZ1 gene lead to cervical dystonia. CIZ1 expression is increased in cancers and rheumatoid arthritis. In this review, we will summarize the biological functions and molecular mechanisms of CIZ1 in these physiological and pathological processes. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Open AccessReview
Noncoding RNA Expression Aberration Is Associated with Cancer Progression and Is a Potential Biomarker in Esophageal Squamous Cell Carcinoma
Int. J. Mol. Sci. 2015, 16(11), 27824-27834; https://doi.org/10.3390/ijms161126060 - 24 Nov 2015
Cited by 36 | Viewed by 3998
Abstract
Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs) function as key epigenetic regulators of gene expression and are [...] Read more.
Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs) function as key epigenetic regulators of gene expression and are implicated in various physiological processes. Unambiguous evidence indicates that dysregulation of ncRNAs is deeply implicated in carcinogenesis, cancer progression and metastases of various cancers, including ESCC. The current review summarizes recent findings on the ncRNA-mediated mechanisms underlying the characteristic behaviors of ESCC that will help support the development of biomarkers and the design of novel therapeutic strategies. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessReview
Spatial Regulation of Root Growth: Placing the Plant TOR Pathway in a Developmental Perspective
Int. J. Mol. Sci. 2015, 16(8), 19671-19697; https://doi.org/10.3390/ijms160819671 - 19 Aug 2015
Cited by 23 | Viewed by 4824
Abstract
Plant cells contain specialized structures, such as a cell wall and a large vacuole, which play a major role in cell growth. Roots follow an organized pattern of development, making them the organs of choice for studying the spatio-temporal regulation of cell proliferation [...] Read more.
Plant cells contain specialized structures, such as a cell wall and a large vacuole, which play a major role in cell growth. Roots follow an organized pattern of development, making them the organs of choice for studying the spatio-temporal regulation of cell proliferation and growth in plants. During root growth, cells originate from the initials surrounding the quiescent center, proliferate in the division zone of the meristem, and then increase in length in the elongation zone, reaching their final size and differentiation stage in the mature zone. Phytohormones, especially auxins and cytokinins, control the dynamic balance between cell division and differentiation and therefore organ size. Plant growth is also regulated by metabolites and nutrients, such as the sugars produced by photosynthesis or nitrate assimilated from the soil. Recent literature has shown that the conserved eukaryotic TOR (target of rapamycin) kinase pathway plays an important role in orchestrating plant growth. We will summarize how the regulation of cell proliferation and cell expansion by phytohormones are at the heart of root growth and then discuss recent data indicating that the TOR pathway integrates hormonal and nutritive signals to orchestrate root growth. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Graphical abstract

Open AccessReview
The Role of Hypoxia-Induced miR-210 in Cancer Progression
Int. J. Mol. Sci. 2015, 16(3), 6353-6372; https://doi.org/10.3390/ijms16036353 - 19 Mar 2015
Cited by 100 | Viewed by 3901
Abstract
Prolonged hypoxia, the event of insufficient oxygen, is known to upregulate tumor development and growth by promoting the formation of a neoplastic environment. The recent discovery that a subset of cellular microRNAs (miRs) are upregulated during hypoxia, where they function to promote tumor [...] Read more.
Prolonged hypoxia, the event of insufficient oxygen, is known to upregulate tumor development and growth by promoting the formation of a neoplastic environment. The recent discovery that a subset of cellular microRNAs (miRs) are upregulated during hypoxia, where they function to promote tumor development, highlights the importance of hypoxia-induced miRs as targets for continued investigation. miRs are short, non-coding transcripts involved in gene expression and regulation. Under hypoxic conditions, miR-210 becomes highly upregulated in response to hypoxia inducing factors (HIFs). HIF-1α drives miR-210’s overexpression and the resultant alteration of cellular processes, including cell cycle regulation, mitochondria function, apoptosis, angiogenesis and metastasis. Here we discuss hypoxia-induced dysregulation of miR-210 and the resultant changes in miR-210 protein targets that regulate cancer progression. Potential methods of targeting miR-210 as a therapeutic tool are also explored. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
Show Figures

Figure 1

Back to TopTop