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Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers

Ray, Animesh and Kunhiraman, Haritha and Perera, Ranjan J. (2021) Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers. Frontiers in Oncology, 10 . Art. No. 628367. ISSN 2234-943X. PMCID PMC7897698.

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Cancer initiation, progression, and metastasis leverage many regulatory agents, such as signaling molecules, transcription factors, and regulatory RNA molecules. Among these, regulatory non-coding RNAs have emerged as molecules that control multiple cancer types and their pathologic properties. The human microRNA-211 (MIR211) is one such molecule, which affects several cancer types, including melanoma, glioblastoma, lung adenocarcinomas, breast, ovarian, prostate, and colorectal carcinoma. Previous studies suggested that in certain tumors MIR211 acts as a tumor suppressor while in others it behaves as an oncogenic regulator. Here we summarize the known molecular genetic mechanisms that regulate MIR211 gene expression and molecular pathways that are in turn controlled by MIR211 itself. We discuss how cellular and epigenetic contexts modulate the biological effects of MIR211, which exhibit pleiotropic effects. For example, up-regulation of MIR211 expression down-regulates Warburg effect in melanoma tumor cells associated with an inhibition of the growth of human melanoma cells in vitro, and yet these conditions robustly increase tumor growth in xenografted mice. Signaling through the DUSP6-ERK5 pathway is modulated by MIR211 in BRAF^(V600E) driven melanoma tumors, and this function is involved in the resistance of tumor cells to the BRAF inhibitor, Vemurafenib. We discuss several alternate but testable models, involving stochastic cell-to-cell expression heterogeneity due to multiple equilibria involving feedback circuits, intracellular communication, and genetic variation at miRNA target sties, to reconcile the paradoxical effects of MIR211 on tumorigenesis. Understanding the precise role of this miRNA is crucial to understanding the genetic basis of melanoma as well as the other cancer types where this regulatory molecule has important influences. We hope this review will inspire novel directions in this field.

Item Type:Article
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URLURL TypeDescription CentralArticle
Ray, Animesh0000-0002-0120-5820
Perera, Ranjan J.0000-0002-5926-3687
Additional Information:© 2021 Ray, Kunhiraman and Perera. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 11 November 2020; Accepted: 21 December 2020; Published: 08 February 2021. We would like to thank Drs. Carmit Levy and Tamar Golan for their initial suggestion and comments on this manuscript. This study was supported by P30 CA006973 (JHU SKCCC) and Florida Department of Health, Bankhead-Coley Cancer Research Program (5BC08) to RP, and CDMRP/DTRA grant W81XWH-16-1-0170 to AR. Author Contributions: AR and RP incepted the idea on the paradoxical behavior of the MIR-211 in melanoma and other cancers. All authors (AR, RP, and HK) contributed to the writing. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Funding AgencyGrant Number
NIHP30 CA006973
Florida Department of HealthUNSPECIFIED
Bankhead-Coley Cancer Research Program5BC08
Defense Threat Reduction Agency (DTRA)W81XWH-16-1-0170
Subject Keywords:microRNA-211, melanoma, tumor-promoter, tumor suppresser, epigenetics, miRNA, bistability, MIR211
PubMed Central ID:PMC7897698
Record Number:CaltechAUTHORS:20210302-125647289
Persistent URL:
Official Citation:Ray A, Kunhiraman H and Perera RJ (2021) The Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers. Front. Oncol. 10:628367. doi: 10.3389/fonc.2020.628367
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108273
Deposited By: Tony Diaz
Deposited On:02 Mar 2021 21:09
Last Modified:02 Mar 2021 21:09

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