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Interrelation between MicroRNA & Cancer
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Interrelation between MicroRNA & 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 (31 August 2023) | Viewed by 7658

Special Issue Editor

Dr. Patrick Baril

E-Mail Website
Guest Editor
1. Centre de Biophysique Moléculaire, CNRS-UPR4301, 45071 Orléans, France
2. Faculté des Sciences, Colléguim Sciences et Techniques, Université d’Orléans, 45071 Orléans, France
Interests: biology; RNA; cancer

Special Issue Information

Dear Colleagues,

Beginning with the discovery of miRNA in the mid-1990s as a result of outstanding studies aimed at identifying novel heterochronic genes involved in the larval development of C. Elegans, it is now well established that miRNAs are a class of non-coding RNAs that bind to their target mRNAs by a base pairing, inducing mRNA degradation and/or translation inhibition. Each miRNA is believed to regulate up to several hundred targets, shaping the functionality of a complex network of coding genes to orchestrate essential biological responses such as cellular differentiation, proliferation and apoptosis. This evolutionarily conserved type of interaction between one miRNA and several mRNAs has attracted great attention in the field of RNA therapeutics, in the belief that the modulation of the expression of one deregulated miRNA might be sufficient to restore the correct expression of multiple deregulated target genes responsible for cancer progression. Many preclinical studies in cancer have proved that the concept is reliable, since the delivery of synthetic oligonucleotide miRNA mimics or inhibitors ameliorates or even reverses the pathological state of cancer. However, despite this tremendous progress, the translation of miRNA-based technologies into the clinic is still limited by their delivery to targeted cancer tissues and by the misunderstanding of the dynamic regulation of miRNA during cancer development. In this context, miRNA imaging modalities have been found as a reliable approach to monitor the spatiotemporal activity of miRNAs in animal models of cancer, providing a unique opportunity to define better therapeutic windows for optimized miRNA-based therapy interventions, as well as for a better understanding of the complexity of miRNA biology. Beyond this, miRNAs have also been proved to be reliable markers for cancer diagnosis, mainly because of their great stability in body samples and also because the pattern of miRNA secretion from cancer cells reflects the stage of disease progression.

In this Special Issue, we would like to encourage the publication of manuscripts dealing with mechanistic studies of miRNAs in cancer biology in general, with particular emphasis on the control of temporally dysregulated cellular signaling pathways during cancer development. Tools dedicated to capturing the dynamic expression of miRNAs at the body, cellular and extracellular levels are of particular interest. Manuscripts dealing with miRNA therapeutics, from the development of miRNA-delivery carriers, to intra- and extracellular trafficking and/or the recycling of miRNA in cancer cells will be appreciated. Finally, studies dealing with miRNA diagnosis in cancer fluid (blood, saliva, urine, gastric juices, etc.) for the better staging of cancer progression will be also regarded.

Dr. Patrick Baril
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

  • miRNA biology
  • cancer
  • therapeutic
  • trafficking
  • exosome
  • recycling
  • diagnosis

Published Papers (5 papers)

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Research

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16 pages, 2703 KiB  
Article
Synergy of the microRNA Ratio as a Promising Diagnosis Biomarker for Mucinous Borderline and Malignant Ovarian Tumors
by Enora Dolivet, Léopold Gaichies, Corinne Jeanne, Céline Bazille, Mélanie Briand, Mégane Vernon, Florence Giffard, Frédéric Leprêtre, Laurent Poulain, Christophe Denoyelle, Nicolas Vigneron and Raffaèle Fauvet
Int. J. Mol. Sci. 2023, 24(21), 16016; https://doi.org/10.3390/ijms242116016 - 6 Nov 2023
Viewed by 1157
Abstract
Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival [...] Read more.
Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival of 11% for advanced stages (III/IV). At the early stages, these malignant forms are clinically difficult to distinguish from borderline (15%) and benign (80%) forms with a better prognosis due to the large size and heterogeneity of mucinous tumors. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in tumor progression and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, the comparison of miRNA microarray expression profiles between malignant and borderline tumor FFPE samples identified 10 down-regulated and 5 up-regulated malignant miRNAs, which were validated by individual RT-qPCR. To overcome normalization issues and to improve the accuracy of the results, a ratio analysis combining paired up-regulated and down-regulated miRNAs was performed. Although 21/50 miRNA expression ratios were significantly different between malignant and borderline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 pairs of miRNA ratios (double ratio) showed high discriminatory potential, with 100% of accuracy in distinguishing malignant and borderline ovarian tumors, which suggests that miRNAs may hold significant clinical potential as a diagnostic tool. In summary, these ratio miRNA-based signatures may help to improve the precision of histological diagnosis, likely to provide a preoperative diagnosis in order to adapt surgical procedures. Full article
(This article belongs to the Special Issue Interrelation between MicroRNA & Cancer)
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16 pages, 3456 KiB  
Article
Identification of Mir-182-3p/FLI-1 Axis as a Key Signaling in Immune Response in Cervical Cancer: A Comprehensive Bioinformatic Analysis
by Eric Genaro Salmerón-Bárcenas, Miguel Angel Mendoza-Catalan, Ángela Uray Ramírez-Bautista, Rafael Acxel Lozano-Santos, Francisco Israel Torres-Rojas, Pedro Antonio Ávila-López and Ana Elvira Zacapala-Gómez
Int. J. Mol. Sci. 2023, 24(7), 6032; https://doi.org/10.3390/ijms24076032 - 23 Mar 2023
Cited by 1 | Viewed by 1767
Abstract
miRNAs modulate gene expression and play critical functions as oncomiRs or tumor suppressors. The miR-182-3p is important in chemoresistance and cancer progression in breast, lung, osteosarcoma, and ovarian cancer. However, the role of miR-182-3p in cervical cancer (CC) has not been elucidated. Aim: [...] Read more.
miRNAs modulate gene expression and play critical functions as oncomiRs or tumor suppressors. The miR-182-3p is important in chemoresistance and cancer progression in breast, lung, osteosarcoma, and ovarian cancer. However, the role of miR-182-3p in cervical cancer (CC) has not been elucidated. Aim: To analyze the role of miR-182-3p in CC through a comprehensive bioinformatic analysis. Methods: Gene Expression Omnibus (GEO) databases were used for the expression analysis. The mRNA targets of miR-182-3p were identified using miRDB, TargetScanHuman, and miRPathDB. The prediction of island CpG was performed using the MethPrimer program. The transcription factor binding sites in the FLI-1 promoter were identified using ConSite+, Alibaba2, and ALGGEN-PROMO. The protein–protein interaction (PPI) analysis was performed in STRING 11.5. Results: miR-182-3p was significantly overexpressed in CC patients and has potential as a diagnostic. We identified 330 targets of miR-182-3p including FLI-1, which downregulates its expression in CC. Additionally, the aberrant methylation of the FLI-1 promoter and Ap2a transcription factor could be involved in downregulating FLI1 expression. Finally, we found that FLI-1 is a possible key gene in the immune response in CC. Conclusions: The miR-182-3p/FLI-1 axis plays a critical role in immune response in CC. Full article
(This article belongs to the Special Issue Interrelation between MicroRNA & Cancer)
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Review

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15 pages, 1211 KiB  
Review
TET Enzymes and 5hmC Levels in Carcinogenesis and Progression of Breast Cancer: Potential Therapeutic Targets
by Eric Genaro Salmerón-Bárcenas, Ana Elvira Zacapala-Gómez, Francisco Israel Torres-Rojas, Verónica Antonio-Véjar, Pedro Antonio Ávila-López, Christian Johana Baños-Hernández, Hober Nelson Núñez-Martínez, Roberto Dircio-Maldonado, Dinorah Nashely Martínez-Carrillo, Julio Ortiz-Ortiz and Hilda Jiménez-Wences
Int. J. Mol. Sci. 2024, 25(1), 272; https://doi.org/10.3390/ijms25010272 - 24 Dec 2023
Cited by 1 | Viewed by 1464
Abstract
Breast Cancer (BC) was the most common female cancer in incidence and mortality worldwide in 2020. Similarly, BC was the top female cancer in the USA in 2022. Risk factors include earlier age at menarche, oral contraceptive use, hormone replacement therapy, high body [...] Read more.
Breast Cancer (BC) was the most common female cancer in incidence and mortality worldwide in 2020. Similarly, BC was the top female cancer in the USA in 2022. Risk factors include earlier age at menarche, oral contraceptive use, hormone replacement therapy, high body mass index, and mutations in BRCA1/2 genes, among others. BC is classified into Luminal A, Luminal B, HER2-like, and Basal-like subtypes. These BC subtypes present differences in gene expression signatures, which can impact clinical behavior, treatment response, aggressiveness, metastasis, and survival of patients. Therefore, it is necessary to understand the epigenetic molecular mechanism of transcriptional regulation in BC, such as DNA demethylation. Ten-Eleven Translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) on DNA, which in turn inhibits or promotes the gene expression. Interestingly, the expression of TET enzymes as well as the levels of the 5hmC epigenetic mark are altered in several types of human cancers, including BC. Several studies have demonstrated that TET enzymes and 5hmC play a key role in the regulation of gene expression in BC, directly (dependent or independent of DNA de-methylation) or indirectly (via interaction with other proteins such as transcription factors). In this review, we describe our recent understanding of the regulatory and physiological function of the TET enzymes, as well as their potential role as biomarkers in BC biology. Full article
(This article belongs to the Special Issue Interrelation between MicroRNA & Cancer)
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29 pages, 2753 KiB  
Review
Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis
by Raquel Nogueras Pérez, Noelia Heredia-Nicolás, Laura de Lara-Peña, Julia López de Andrés, Juan Antonio Marchal, Gema Jiménez and Carmen Griñán-Lisón
Int. J. Mol. Sci. 2023, 24(21), 16010; https://doi.org/10.3390/ijms242116010 - 6 Nov 2023
Viewed by 1373
Abstract
Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC [...] Read more.
Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs’ self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance. Full article
(This article belongs to the Special Issue Interrelation between MicroRNA & Cancer)
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18 pages, 2199 KiB  
Review
EV-miRNA-Mediated Intercellular Communication in the Breast Tumor Microenvironment
by Francisca Sepúlveda, Cristina Mayorga-Lobos, Kevin Guzmán, Eduardo Durán-Jara and Lorena Lobos-González
Int. J. Mol. Sci. 2023, 24(17), 13085; https://doi.org/10.3390/ijms241713085 - 23 Aug 2023
Cited by 2 | Viewed by 1332
Abstract
Cancer research has prioritized the study of the tumor microenvironment (TME) as a crucial area of investigation. Understanding the communication between tumor cells and the various cell types within the TME has become a focal point. Bidirectional communication processes between these cells support [...] Read more.
Cancer research has prioritized the study of the tumor microenvironment (TME) as a crucial area of investigation. Understanding the communication between tumor cells and the various cell types within the TME has become a focal point. Bidirectional communication processes between these cells support cellular transformation, as well as the survival, invasion, and metastatic dissemination of tumor cells. Extracellular vesicles are lipid bilayer structures secreted by cells that emerge as important mediators of this cell-to-cell communication. EVs transfer their molecular cargo, including proteins and nucleic acids, and particularly microRNAs, which play critical roles in intercellular communication. Tumor-derived EVs, for example, can promote angiogenesis and enhance endothelial permeability by delivering specific miRNAs. Moreover, adipocytes, a significant component of the breast stroma, exhibit high EV secretory activity, which can then modulate metabolic processes, promoting the growth, proliferation, and migration of tumor cells. Comprehensive studies investigating the involvement of EVs and their miRNA cargo in the TME, as well as their underlying mechanisms driving tumoral capacities, are necessary for a deeper understanding of these complex interactions. Such knowledge holds promise for the development of novel diagnostic and therapeutic strategies in cancer treatment. Full article
(This article belongs to the Special Issue Interrelation between MicroRNA & Cancer)
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