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Strategic Molecular Biomarkers and MicroRNAs in Cancer
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Strategic Molecular Biomarkers and MicroRNAs in Cancer

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

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 19731

Special Issue Editor

Dr. Simona Olimpia Dima

E-Mail Website
Guest Editor
Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
Interests: surgery; translational medicine; oncogenomic

Special Issue Information

Dear Colleagues,

Growing evidence is showing that various miRNAs are involved in the tumorigenesis, progression and metastases of various types of malignancies. Currently, many studies are focusing on the identification and validation of ”individual miRNAs” or “signatures of miRNAs” as novel diagnostic or prognostic miRNA-based biomarkers of cancer. Moreover, due their stability in different bodily fluids, miRNAs are potential liquid biopsy candidates for noninvasive cancer detection.

In addition, MiRNAs could help to predict the effectiveness of therapy, monitor the response to treatment, and, based on this information, could identify personalized cytotoxic therapies.

The focus of this Special Issue is to identify original and review articles that provide an update on the progress of miRNA translation in multimarker clinical models for the diagnosis, prognosis and evaluation of treatment response in different types of cancer.

Dr. Simona Olimpia Dima
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. 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

  • microRNA
  • biomarkers
  • epithelial-to-mesenchymal transition
  • molecular cancer biology
  • metastasis
  • personalized medicine

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Published Papers (5 papers)

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Research

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22 pages, 10200 KiB  
Article
Cell State Transitions and Phenotypic Heterogeneity in Luminal Breast Cancer Implicating MicroRNAs as Potential Regulators
by Vinitha Richard, Madhumathy G. Nair, Vishnu S. Jaikumar, Sara Jones, Jyothi S. Prabhu and Michael J. Kerin
Int. J. Mol. Sci. 2023, 24(4), 3497; https://doi.org/10.3390/ijms24043497 - 9 Feb 2023
Cited by 4 | Viewed by 3210
Abstract
Luminal breast cancer subtypes respond poorly to endocrine and trastuzumab treatments due to cellular heterogeneity arising from the phenotype transitions, accounted for mainly by the loss of receptor expression. The origins of basal-like and human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer [...] Read more.
Luminal breast cancer subtypes respond poorly to endocrine and trastuzumab treatments due to cellular heterogeneity arising from the phenotype transitions, accounted for mainly by the loss of receptor expression. The origins of basal-like and human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer subtypes have been attributed to genetic and protein modifications in stem-like cells and luminal progenitor cell populations, respectively. The post-transcriptional regulation of protein expression is known to be influenced by microRNAs (miRNAs) that are deemed to be master regulators of several biological processes in breast tumorigenesis and progression. Our objective was to identify the fractions of luminal breast cancer cells that share stemness potentials and marker profiles and to elucidate the molecular regulatory mechanism that drives transitions between fractions, leading to receptor discordances. Established breast cancer cell lines of all prominent subtypes were screened for the expression of putative cancer stem cell (CSC) markers and drug transporter proteins using a side population (SP) assay. Flow-cytometry-sorted fractions of luminal cancer cells implanted in immunocompromised mice generated a pre-clinical estrogen receptor alpha (ERα+) animal model with multiple tumorigenic fractions displaying differential expression of drug transporters and hormone receptors. Despite an abundance of estrogen receptor 1 (ESR1) gene transcripts, few fractions transitioned to the triple-negative breast cancer (TNBC) phenotype with a visible loss of ER protein expression and a distinct microRNA expression profile that is reportedly enriched in breast CSCs. The translation of this study has the potential to provide novel therapeutic miRNA-based targets to counter the dreaded subtype transitions and the failure of antihormonal therapies in the luminal breast cancer subtype. Full article
(This article belongs to the Special Issue Strategic Molecular Biomarkers and MicroRNAs in Cancer)
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20 pages, 6191 KiB  
Article
The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma
by Nicoleta-Raluca Chelaru, Andrei Chiosa, Andrei Sorop, Andreea Spiridon, Florentina Cojocaru, Dan Domocos, Dana Cucu, Irinel Popescu and Simona-Olimpia Dima
Int. J. Mol. Sci. 2022, 23(16), 9045; https://doi.org/10.3390/ijms23169045 - 12 Aug 2022
Cited by 10 | Viewed by 3590
Abstract
Pancreatic adenocarcinoma (PDAC) has low survival rates worldwide due to its tendency to be detected late and its characteristic desmoplastic reaction, which slows the use of targeted therapies. As such, the discovery of new connections between genes and the clinicopathological parameters contribute to [...] Read more.
Pancreatic adenocarcinoma (PDAC) has low survival rates worldwide due to its tendency to be detected late and its characteristic desmoplastic reaction, which slows the use of targeted therapies. As such, the discovery of new connections between genes and the clinicopathological parameters contribute to the search for new biomarkers or targets for therapy. Transient receptor potential (TRP) channels are promising tools for cancer therapy or markers for PDAC. Therefore, in this study, we selected several genes encoding TRP proteins previously reported in cellular models, namely, Transient Receptor Potential Cation Channel Subfamily V Member 6 (TRPV6), Transient receptor potential ankyrin 1 (TRPA1), and Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), as well as the TRPM8 Channel Associated Factor 1 (TCAF1) and TRPM8 Channel Associated Factor 2 (TCAF2) proteins, as regulatory factors. We analyzed the expression levels of tumors from patients enrolled in public datasets and confirmed the results with a validation cohort of PDAC patients enrolled in the Clinical Institute Fundeni, Romania. We found significantly higher expression levels of TRPA1, TRPM8, and TCAF1/F2 in tumoral tissues compared to normal tissues, but lower expression levels of TRPV6, suggesting that TRP channels have either tumor-suppressive or oncogenic roles. The expression levels were correlated with the tumoral stages and are related to the genes involved in calcium homeostasis (Calbindin 1 or S100A4) or to proteins participating in metastasis (PTPN1). We conclude that the selected TRP proteins provide new insights in the search for targets and biomarkers needed for therapeutic strategies for PDAC treatment. Full article
(This article belongs to the Special Issue Strategic Molecular Biomarkers and MicroRNAs in Cancer)
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16 pages, 2673 KiB  
Article
Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis
by Mihaela Chivu-Economescu, Laura G. Necula, Lilia Matei, Denisa Dragu, Coralia Bleotu, Andrei Sorop, Vlad Herlea, Simona Dima, Irinel Popescu and Carmen C. Diaconu
Int. J. Mol. Sci. 2022, 23(6), 3214; https://doi.org/10.3390/ijms23063214 - 16 Mar 2022
Cited by 26 | Viewed by 4734
Abstract
Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. Aiming to fill this gap, we performed a bioinformatics assessment on [...] Read more.
Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. Aiming to fill this gap, we performed a bioinformatics assessment on our data and two additional GEO microarray profiles, followed by a deep analysis of the 40 differentially expressed genes identified. PPI network analysis and MCODE plug-in pointed out nine upregulated hub genes coding for proteins from the collagen family (COL12A1, COL5A2, and COL10A1) or involved in the assembly (BGN) or degradation of collagens (CTHRC1), and also associated with cell adhesion (THBS2 and SPP1) and extracellular matrix degradation (FAP, SULF1). Those genes were highly upregulated at the mRNA and protein level, the increase being correlated with pathological T stages. The high expression of BGN (p = 8 × 10−12), THBS2 (p = 1.2 × 10−6), CTHRC1 (p = 1.1 × 10−4), SULF1 (p = 3.8 × 10−4), COL5A1 (p = 1.3 × 10−4), COL10A1 (p = 5.7 × 10−4), COL12A1 (p = 2 × 10−3) correlated with poor overall survival and an immune infiltrate based especially on immunosuppressive M2 macrophages (p-value range 4.82 × 10−7–1.63 × 10−13). Our results emphasize that these genes could be candidate biomarkers for GC progression and prognosis and new therapeutic targets. Full article
(This article belongs to the Special Issue Strategic Molecular Biomarkers and MicroRNAs in Cancer)
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Review

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21 pages, 1421 KiB  
Review
The Link between Diabetes, Pancreatic Tumors, and miRNAs—New Players for Diagnosis and Therapy?
by Małgorzata Kozłowska and Agnieszka Śliwińska
Int. J. Mol. Sci. 2023, 24(12), 10252; https://doi.org/10.3390/ijms241210252 - 16 Jun 2023
Cited by 6 | Viewed by 3242
Abstract
Despite significant progress in medicine, pancreatic cancer is one of the most tardily diagnosed cancer and is consequently associated with a poor prognosis and a low survival rate. The asymptomatic clinical picture and the lack of relevant diagnostic markers for the early stages [...] Read more.
Despite significant progress in medicine, pancreatic cancer is one of the most tardily diagnosed cancer and is consequently associated with a poor prognosis and a low survival rate. The asymptomatic clinical picture and the lack of relevant diagnostic markers for the early stages of pancreatic cancer are believed to be the major constraints behind an accurate diagnosis of this disease. Furthermore, underlying mechanisms of pancreatic cancer development are still poorly recognized. It is well accepted that diabetes increases the risk of pancreatic cancer development, however the precise mechanisms are weakly investigated. Recent studies are focused on microRNAs as a causative factor of pancreatic cancer. This review aims to provide an overview of the current knowledge of pancreatic cancer and diabetes-associated microRNAs, and their potential in diagnosis and therapy. miR-96, miR-124, miR-21, and miR-10a were identified as promising biomarkers for early pancreatic cancer prediction. miR-26a, miR-101, and miR-200b carry therapeutic potential, as they not only regulate significant biological pathways, including the TGF-β and PI3K/AKT, but their re-expression contributes to the improvement of the prognosis by reducing invasiveness or chemoresistance. In diabetes, there are also changes in the expression of microRNAs, such as in miR-145, miR-29c, and miR-143. These microRNAs are involved, among others, in insulin signaling, including IRS-1 and AKT (miR-145), glucose homeostasis (hsa-miR-21), and glucose reuptake and gluconeogenesis (miR-29c). Although, changes in the expression of the same microRNAs are observed in both pancreatic cancer and diabetes, they exert different molecular effects. For example, miR-181a is upregulated in both pancreatic cancer and diabetes mellitus, but in diabetes it contributes to insulin resistance, whereas in pancreatic cancer it promotes tumor cell migration, respectively. To conclude, dysregulated microRNAs in diabetes affect crucial cellular processes that are involved in pancreatic cancer development and progression. Full article
(This article belongs to the Special Issue Strategic Molecular Biomarkers and MicroRNAs in Cancer)
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14 pages, 1041 KiB  
Review
Focus on PD-1/PD-L1 as a Therapeutic Target in Ovarian Cancer
by Adrian Dumitru, Elena-Codruta Dobrica, Adina Croitoru, Sanda Maria Cretoiu and Bogdan Severus Gaspar
Int. J. Mol. Sci. 2022, 23(20), 12067; https://doi.org/10.3390/ijms232012067 - 11 Oct 2022
Cited by 27 | Viewed by 3849
Abstract
Ovarian cancer is considered one of the most aggressive and deadliest gynecological malignancies worldwide. Unfortunately, the therapeutic methods that are considered the gold standard at this moment are associated with frequent recurrences. Survival in ovarian cancer is associated with the presence of a [...] Read more.
Ovarian cancer is considered one of the most aggressive and deadliest gynecological malignancies worldwide. Unfortunately, the therapeutic methods that are considered the gold standard at this moment are associated with frequent recurrences. Survival in ovarian cancer is associated with the presence of a high number of intra tumor infiltrating lymphocytes (TILs). Therefore, immunomodulation is considered to have an important role in cancer treatment, and immune checkpoint inhibitors may be useful for restoring T cell-mediated antitumor immunity. However, the data presented in the literature until now are not sufficient to allow for the identification and selection of patients who really respond to immunotherapy among those with ovarian cancer. Although there are some studies with favorable results, more prospective trials are needed in this sense. This review focuses on the current and future perspectives of PD-1/L1 blockade in ovarian cancer and analyzes the most important immune checkpoint inhibitors used, with the aim of achieving optimal clinical outcomes. Future studies and trials are needed to maximize the efficacy of immune checkpoint blockade therapy in ovarian cancer, as well as in all cancers, in general. Full article
(This article belongs to the Special Issue Strategic Molecular Biomarkers and MicroRNAs in Cancer)
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