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MicroRNAs in Cancer: Biomarkers, Functions and Therapies
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MicroRNAs in Cancer: Biomarkers, Functions and Therapies

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 12096

Special Issue Editor

Dr. Viswanathan Palanisamy

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
Interests: RNA-binding proteins; miRNAs; mRNA turnover; translation; post-transcriptional gene regulation and cancer

Special Issue Information

Dear Colleagues,

Regulation of gene expression is a multi-step biological process, mainly controlled at the co- or post-transcriptional levels in eukaryotes. A dysfunctional post-transcriptional gene regulation leads to aberrant expression of oncoproteins to promote cancers. MicroRNAs are small non-coding RNAs that control gene expression by targeting mRNAs at the post-transcriptional level. Cancer cells encompass thousands of miRNAs that are either amplified or downregulated, which become oncomiRs or tumor suppressors, respectively. One of the significant steps in the behavior of miRNAs is the activation or the repression of their target genes. Thus, miRNAs can serve as biomarkers, regulating gene expression and being used as therapeutic molecules to target oncoproteins in cancers.

In this Special Issue of Cells, we collect original discoveries and reviews related to miRNAs as potential biomarkers in cancers, function as oncomiRs or tumor suppressors, and as therapeutic targets for cancers. Studies looking at the functional role of miRNAs in mRNA turnover and translational control will be taken into consideration. Specific topics in this Special Issue include the cancer relevance of regulation of miRNA expression, miRNAs as predictive biomarkers in cancer tissues and cells, amiRNA-mediated post-transcriptional changes at the functional level, which modulate transcriptomics and proteomics, and miRNAs as cancer therapeutics.  

This Special Issue should serve as an opportunity for molecular and cancer biologists to share their experimental data and theories to help understand the novel role of miRNAs in cancers for future innovative discoveries.

We look forward to your contributions to this Special Issue.

Dr. Viswanathan Palanisamy
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 submissions that pass pre-check are 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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • miRNAs
  • biomarkers
  • oncomiRs
  • tumor suppressors
  • miRNA therapeutics
  • mRNA turnover
  • mRNA translational control
  • post-transcriptional gene regulation
  • cancer
  • transcriptional activation of miRNAs in cancer

Published Papers (5 papers)

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Research

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20 pages, 4087 KiB  
Article
ECM Substrates Impact RNAi Localization at Adherens Junctions of Colon Epithelial Cells
by Amanda C. Daulagala and Antonis Kourtidis
Cells 2022, 11(23), 3740; https://doi.org/10.3390/cells11233740 - 23 Nov 2022
Cited by 3 | Viewed by 1735
Abstract
The extracellular matrix (ECM) plays crucial roles in tissue homeostasis. Abnormalities in ECM composition are associated with pathological conditions, such as fibrosis and cancer. These ECM alterations are sensed by the epithelium and can influence its behavior through crosstalk with other mechanosensitive complexes, [...] Read more.
The extracellular matrix (ECM) plays crucial roles in tissue homeostasis. Abnormalities in ECM composition are associated with pathological conditions, such as fibrosis and cancer. These ECM alterations are sensed by the epithelium and can influence its behavior through crosstalk with other mechanosensitive complexes, including the adherens junctions (AJs). We have previously shown that the AJs, through their component PLEKHA7, recruit the RNAi machinery to regulate miRNA levels and function. We have particularly shown that the junctional localization of RNAi components is critical for their function. Here, we investigated whether different ECM substrates can influence the junctional localization of RNAi complexes. To do this, we plated colon epithelial Caco2 cells on four key ECM substrates found in the colon under normal or pathogenic conditions, namely laminin, fibronectin, collagen I, and collagen IV, and we examined the subcellular distribution of PLEKHA7, and of the key RNAi components AGO2 and DROSHA. Fibronectin and collagen I negatively impacted the junctional localization of PLEKHA7, AGO2, and DROSHA when compared to laminin. Furthermore, fibronectin, collagen I, and collagen IV disrupted interactions of AGO2 and DROSHA with their essential partners GW182 and DGCR8, respectively, both at AJs and throughout the cell. Combinations of all substrates with fibronectin also negatively impacted junctional localization of PLEKHA7 and AGO2. Additionally, collagen I triggered accumulation of DROSHA at tri-cellular junctions, while both collagen I and collagen IV resulted in DROSHA accumulation at basal areas of cell–cell contact. Altogether, fibronectin and collagens I and IV, which are elevated in the stroma of fibrotic and cancerous tissues, altered localization patterns and disrupted complex formation of PLEKHA7 and RNAi components. Combined with our prior studies showing that apical junctional localization of the PLEKHA7-RNAi complex is critical for regulating tumor-suppressing miRNAs, this work points to a yet unstudied mechanism that could contribute to epithelial cell transformation. Full article
(This article belongs to the Special Issue MicroRNAs in Cancer: Biomarkers, Functions and Therapies)
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16 pages, 647 KiB  
Article
Circulating Serum MiRNA-8074 as a Novel Prognostic Biomarker for Multiple Myeloma
by Aneta Szudy-Szczyrek, Radosław Mlak, Michał Mielnik, Marcin Mazurek, Sylwia Chocholska, Martyna Podgajna, Michał Szczyrek, Iwona Homa-Mlak, Teresa Małecka-Massalska and Marek Hus
Cells 2022, 11(4), 752; https://doi.org/10.3390/cells11040752 - 21 Feb 2022
Cited by 4 | Viewed by 2404
Abstract
MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in [...] Read more.
MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16–3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie–Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high β2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20–7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients. Full article
(This article belongs to the Special Issue MicroRNAs in Cancer: Biomarkers, Functions and Therapies)
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Review

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14 pages, 1662 KiB  
Review
MicroRNAs in Cancer and Cardiovascular Disease
by Mirolyuba Ilieva, Riccardo Panella and Shizuka Uchida
Cells 2022, 11(22), 3551; https://doi.org/10.3390/cells11223551 - 10 Nov 2022
Cited by 15 | Viewed by 2440
Abstract
Although cardiac tumor formation is rare, accumulating evidence suggests that the two leading causes of deaths, cancers, and cardiovascular diseases are similar in terms of pathogenesis, including angiogenesis, immune responses, and fibrosis. These similarities have led to the creation of new exciting field [...] Read more.
Although cardiac tumor formation is rare, accumulating evidence suggests that the two leading causes of deaths, cancers, and cardiovascular diseases are similar in terms of pathogenesis, including angiogenesis, immune responses, and fibrosis. These similarities have led to the creation of new exciting field of study called cardio-oncology. Here, we review the similarities between cancer and cardiovascular disease from the perspective of microRNAs (miRNAs). As miRNAs are well-known regulators of translation by binding to the 3′-untranslated regions (UTRs) of messenger RNAs (mRNAs), we carefully dissect how a specific set of miRNAs are both oncomiRs (miRNAs in cancer) and myomiRs (muscle-related miRNAs). Furthermore, from the standpoint of similar pathogenesis, miRNAs categories related to the similar pathogenesis are discussed; namely, angiomiRs, Immune-miRs, and fibromiRs. Full article
(This article belongs to the Special Issue MicroRNAs in Cancer: Biomarkers, Functions and Therapies)
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22 pages, 1920 KiB  
Review
Mechanisms Controlling MicroRNA Expression in Tumor
by Shipeng Chen, Ya Wang, Dongmei Li, Hui Wang, Xu Zhao, Jing Yang, Longqing Chen, Mengmeng Guo, Juanjuan Zhao, Chao Chen, Ya Zhou, Guiyou Liang and Lin Xu
Cells 2022, 11(18), 2852; https://doi.org/10.3390/cells11182852 - 13 Sep 2022
Cited by 11 | Viewed by 2164
Abstract
MicroRNAs (miRNAs) are widely present in many organisms and regulate the expression of genes in various biological processes such as cell differentiation, metabolism, and development. Numerous studies have shown that miRNAs are abnormally expressed in tumor tissues and are closely associated with tumorigenesis. [...] Read more.
MicroRNAs (miRNAs) are widely present in many organisms and regulate the expression of genes in various biological processes such as cell differentiation, metabolism, and development. Numerous studies have shown that miRNAs are abnormally expressed in tumor tissues and are closely associated with tumorigenesis. MiRNA-based cancer gene therapy has consistently shown promising anti-tumor effects and is recognized as a new field in cancer treatment. So far, some clinical trials involving the treatment of malignancies have been carried out; however, studies of miRNA-based cancer gene therapy are still proceeding slowly. Therefore, furthering our understanding of the regulatory mechanisms of miRNA can bring substantial benefits to the development of miRNA-based gene therapy or other combination therapies and the clinical outcome of patients with cancer. Recent studies have revealed that the aberrant expression of miRNA in tumors is associated with promoter sequence mutation, epigenetic alteration, aberrant RNA modification, etc., showing the complexity of aberrant expression mechanisms of miRNA in tumors. In this paper, we systematically summarized the regulation mechanisms of miRNA expression in tumors, with the aim of providing assistance in the subsequent elucidation of the role of miRNA in tumorigenesis and the development of new strategies for tumor prevention and treatment. Full article
(This article belongs to the Special Issue MicroRNAs in Cancer: Biomarkers, Functions and Therapies)
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22 pages, 2046 KiB  
Review
MicroRNAs and Their Big Therapeutic Impacts: Delivery Strategies for Cancer Intervention
by Charles Holjencin and Andrew Jakymiw
Cells 2022, 11(15), 2332; https://doi.org/10.3390/cells11152332 - 29 Jul 2022
Cited by 19 | Viewed by 2484
Abstract
Three decades have passed from the initial discovery of a microRNA (miRNA) in Caenorhabditis elegans to our current understanding that miRNAs play essential roles in regulating fundamental physiological processes and that their dysregulation can lead to many human pathologies, including cancer. In effect, [...] Read more.
Three decades have passed from the initial discovery of a microRNA (miRNA) in Caenorhabditis elegans to our current understanding that miRNAs play essential roles in regulating fundamental physiological processes and that their dysregulation can lead to many human pathologies, including cancer. In effect, restoration of miRNA expression or downregulation of aberrantly expressed miRNAs using miRNA mimics or anti-miRNA inhibitors (anti-miRs/antimiRs), respectively, continues to show therapeutic potential for the treatment of cancer. Although the manipulation of miRNA expression presents a promising therapeutic strategy for cancer treatment, it is predominantly reliant on nucleic acid-based molecules for their application, which introduces an array of hurdles, with respect to in vivo delivery. Because naked nucleic acids are quickly degraded and/or removed from the body, they require delivery vectors that can help overcome the many barriers presented upon their administration into the bloodstream. As such, in this review, we discuss the strengths and weaknesses of the current state-of-the-art delivery systems, encompassing viral- and nonviral-based systems, with a specific focus on nonviral nanotechnology-based miRNA delivery platforms, including lipid-, polymer-, inorganic-, and extracellular vesicle-based delivery strategies. Moreover, we also shed light on peptide carriers as an emerging technology that shows great promise in being a highly efficacious delivery platform for miRNA-based cancer therapeutics. Full article
(This article belongs to the Special Issue MicroRNAs in Cancer: Biomarkers, Functions and Therapies)
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