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MicroRNA Biology in Cancer Development

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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 (30 June 2020) | Viewed by 31841

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Special Issue Editors

Dr. Rosa Visone

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Guest Editor

Ageing Research Center and Translational Medicine-CeSI-MeT, 66100 Chieti, Italy
Interests: cancer; microRNAs; immunology

Dr. Angelo Veronese

E-Mail Website
Guest Editor

Center for Advanced Studies and Technology (CAST), G. d’Annunzio University, 66100 Chieti, Italy
Interests: cancer; microRNAs; epigenetics; DNA methylation; immuno-oncology

Special Issue Information

Dear Colleagues,

In October 2001, two researcher groups described two "short temporal RNAs (stRNAs)" and their functions as "key regulators of development timing" in Caenorhabditis elegans. Then, in the same volume (Science, 294), another manuscript reported 15 other similar short RNAs conserved between invertebrates and vertebrates that were ultimately named microRNA. Short non-coding RNAs are strictly and temporally regulated and are able to finely adjust cellular gene expression and organism phenotypes.

Following this discovery, the major challenges in this field include determining the upstream and downstream master genes and their mechanisms of action. Study in this area is necessary to improve knowledge related to the clinical management of cancer patients.

Since cancer is the result of seemingly unjustified formation of new tissues in an organoid-like development, microRNAs could be a target for cancer treatments.

This Special Issue aims to provide a comprehensive overview of miRNA biology during neoplastic development considering all of the critical aspects of cancer: metabolism, epigenetics, drug resistance, microenvironment, tolerogenic and stemness features. We particularly encourage studies on the emergent new employment of microRNAs as (i) epigenetic regulators (nuclear activities) and (ii) the cell-to-cell communicators (eosome-mediated microRNA transfer).

Dr. Rosa Visone
Dr. Angelo Veronese
Guest Editors

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
cancer
microRNA biogenesis
microRNA functions
exosome
epigenetics

Published Papers (7 papers)

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Research

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13 pages, 2070 KiB

Open AccessArticle

A Tetra-Panel of Serum Circulating miRNAs for the Diagnosis of the Four Most Prevalent Tumor Types

by Belén Pastor-Navarro, María García-Flores, Antonio Fernández-Serra, Salvador Blanch-Tormo, Fernando Martínez de Juan, Carmen Martínez-Lapiedra, Fernanda Maia de Alcantara, Juan Carlos Peñalver, José Cervera-Deval, José Rubio-Briones, Jaime García-Rupérez and José Antonio López-Guerrero

Int. J. Mol. Sci. 2020, 21(8), 2783; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082783 - 16 Apr 2020

Cited by 9 | Viewed by 3441

Abstract

The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% (p = 0.001) for all 4 tumor types and of 80.8% (p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts. Full article

(This article belongs to the Special Issue MicroRNA Biology in Cancer Development)

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16 pages, 3935 KiB

Open AccessArticle

miR-216a Acts as a Negative Regulator of Breast Cancer by Modulating Stemness Properties and Tumor Microenvironment

by Giuseppina Roscigno, Assunta Cirella, Alessandra Affinito, Cristina Quintavalle, Iolanda Scognamiglio, Francesco Palma, Francesco Ingenito, Silvia Nuzzo, Francesca De Micco, Antonio Cuccuru, Renato Thomas and Gerolama Condorelli

Int. J. Mol. Sci. 2020, 21(7), 2313; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072313 - 27 Mar 2020

Cited by 13 | Viewed by 2885

Abstract

Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in breast cancer stem cells vs. the differentiated counterpart. We demonstrate that overexpression of miR-216a-5p impairs stemness markers, mammosphere formation, ALDH activity, and the level of Toll-like receptor 4 (TLR4), which plays a significant role in breast cancer progression and metastasis by leading to the release of pro-inflammatory molecules, such as interleukin 6 (IL-6). Indeed, miR-216a regulates the crosstalk between cancer cells and the cells of the microenvironment, in particular cancer-associated fibroblasts (CAFs), through regulation of the TLR4/IL6 pathway. Thus, miR-216a has an important role in the regulation of stem phenotype, decreasing stem-like properties and affecting the cross-talk between cancer cells and the tumor microenvironment. Full article

(This article belongs to the Special Issue MicroRNA Biology in Cancer Development)

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16 pages, 4858 KiB

Open AccessArticle

Differentially Expressed microRNAs in MIA PaCa-2 and PANC-1 Pancreas Ductal Adenocarcinoma Cell Lines are Involved in Cancer Stem Cell Regulation

by Ye Shen, Kefeng Pu, Kexiao Zheng, Xiaochuan Ma, Jingyi Qin, Li Jiang and Jiong Li

Int. J. Mol. Sci. 2019, 20(18), 4473; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184473 - 10 Sep 2019

Cited by 13 | Viewed by 6886

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, and thus better understanding of its molecular pathology is crucial for us to devise more effective treatment of this deadly disease. As cancer cell line remains a convenient starting point for discovery and proof-of-concept studies, here we report the miRNA expression characteristics of two cell lines, MIA PaCa-2 and PANC-1, and discovered three miRNAs (miR-7-5p, let-7d, and miR-135b-5p) that are involved in cancer stem cells (CSCs) suppression. After transfection of each miRNA’s mimic into PANC-1 cells which exhibits higher stemness feature than MIA-PaCa-2 cells, partial reduction of CSC surface markers and inhibition of tumor sphere formation were observed. These results enlighten us to consider miRNAs as potential therapeutic agents for pancreatic cancer patients via specific and effective inhibition of CSCs. Full article

(This article belongs to the Special Issue MicroRNA Biology in Cancer Development)

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Graphical abstract

17 pages, 8149 KiB

Open AccessArticle

LncRNA NEAT1 Silenced miR-133b Promotes Migration and Invasion of Breast Cancer Cells

by Xinping Li, Siwei Deng, Xinyao Pang, Yixiao Song, Shiyu Luo, Liang Jin and Yi Pan

Int. J. Mol. Sci. 2019, 20(15), 3616; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20153616 - 24 Jul 2019

Cited by 55 | Viewed by 4035 | Correction

Abstract

Breast cancer, the most prevalent cancer type among women worldwide, remains incurable once metastatic. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in breast cancer by regulating specific genes or proteins. In this study, we found miR-133b was silenced in breast cancer cell lines and in breast cancer tissues, which predicted poor prognosis in breast cancer patients. We also confirmed that lncRNA NEAT1 was up-regulated in breast cancer and inhibited the expression of miR-133b, and identified the mitochondrial protein translocase of inner mitochondrial membrane 17 homolog A (TIMM17A) that serves as the target of miR-133b. Both miR-133b knockdown and TIMM17A overexpression in breast cancer cells promoted cell migration and invasion both in vitro and in vivo. In summary, our findings reveal that miR-133b plays a critical role in breast cancer cell metastasis by targeting TIMM17A. These findings may provide new insights into novel molecular therapeutic targets for breast cancer. Full article

(This article belongs to the Special Issue MicroRNA Biology in Cancer Development)

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Review

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23 pages, 1391 KiB

Open AccessReview

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

by Omid Kooshkaki, Zohre Rezaei, Meysam Rahmati, Parviz Vahedi, Afshin Derakhshani, Oronzo Brunetti, Amir Baghbanzadeh, Behzad Mansoori, Nicola Silvestris and Behzad Baradaran

Int. J. Mol. Sci. 2020, 21(7), 2578; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072578 - 08 Apr 2020

Cited by 39 | Viewed by 7238

Abstract

MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers. Full article

(This article belongs to the Special Issue MicroRNA Biology in Cancer Development)

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17 pages, 1270 KiB

Open AccessReview

The Role of Exo-miRNAs in Cancer: A Focus on Therapeutic and Diagnostic Applications

by Francesco Ingenito, Giuseppina Roscigno, Alessandra Affinito, Silvia Nuzzo, Iolanda Scognamiglio, Cristina Quintavalle and Gerolama Condorelli

Int. J. Mol. Sci. 2019, 20(19), 4687; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194687 - 21 Sep 2019

Cited by 108 | Viewed by 5313

Abstract

Exosomes are extracellular vesicles released into biological fluids where they act as carriers of various molecules, including proteins, lipids, and RNAs, between cells, modulating or perturbing specific physiological processes. Recently, it has been suggested that tumoral cells release excessive amounts of exosomes that, through their cargo, promote tumor progression, stimulating growth, angiogenesis, metastasis, insensitivity to chemotherapy, and immune evasion. Increasing evidence highlights exosomal microRNAs (exo-miRNAs) as important players in tumorigenesis. MicroRNA (miRNA) are a class of small non-coding RNA able to regulate gene expression, targeting multiple mRNAs and inducing translational repression and/or mRNA degradation. Exo-miRNAs are highly stable and easily detectable in biological fluids, and for these reasons, miRNAs are potential cancer biomarkers useful diagnostically and prognostically. Furthermore, since exosomes are natural delivery systems between cells, they can be appropriately modified to carry therapeutic miRNAs to specific recipient cells. Here we summarize the main functions of exo-miRNAs and their possible role for diagnostic and therapeutic applications. Full article

(This article belongs to the Special Issue MicroRNA Biology in Cancer Development)

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