The role of the miR-200 family in epithelial-mesenchymal transition

Abstract

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Genes encoding miRNAs are located in regions of the genome that are commonly amplified, deleted or rearranged. They are commonly dysregulated in human cancers and known to act as oncogenes or tumor suppressors. Members of the miR-200 miRNA family are downregulated in human cancer cells and tumors due to aberrant epigenetic gene silencing and play a critical role in the suppression of epithelial-to-mesenchymal transition (EMT), tumor cell adhesion, migration, invasion and metastasis, by targeting and repressing the expression of key mRNAs that are involved in EMT (ZEB1 and ZEB2), β-catenin/Wnt signaling (β-catenin), EGFR inhibitor resistance (ERRFI-1) and chemoresistance to therapeutic agents (TUBB3). Since the miR-200 family functions as putative tumor suppressors and represent biomarkers for poorly differentiated and aggressive cancers, restoration of miR-200 expression may have therapeutic implications for the treatment of metastatic and drug-resistant tumors.

Anoikis: an emerging hallmark in health and diseases

“…An intriguing feedback loop between ZEB transcription factors and members of the miR200 family [131] in controlling EMT, anoikis resistance and metastasis has been recently elucidated [132]. The expression of ZEB1 is strictly correlated to the miR200 family [131], although they control opposite phenomena, ZEB1 being a crucial EMT activator, whereas miR200 members induce the reverse process, ie epithelial differentiation. Actually, ZEB factors and miR200 reciprocally control their expression in a strict feedback loop [133].…”

“…Actually, ZEB factors and miR200 reciprocally control their expression in a strict feedback loop [133]. Of note, ZEB1 is a key EMT regulator in many human cancers including prostate, colon, breast and pancreatic [132,[134][135][136], while miR200 family members are often down-regulated in cancer cells [131]. Actually, the regulation of EMT by miRNAs is a very general phenomenon not limited to TrkB signalling [137].…”

“…Actually, the regulation of EMT by miRNAs is a very general phenomenon not limited to TrkB signalling [137]. Evidence shows that re-expression of miR200 family members suppresses anoikis resistance in breast cancer cells [131,138,139]. In addition, Penna et al [140] recently showed that during melanoma progression miR214 is up-regulated and positively enhances cell movement and survival to anoikis in vitro as well as metastasis formation in vivo.…”

How to Explain the Contradiction of microRNA 200c Expression and Survival in Solid Tumors?: a Meta-analysis

“…It is documented that the suppression of miRNA200c by interleukin 6 (IL6) drives transformation and tumorigenesis (Rokavec et al, 2012). Increasing evidence also demonstrate that miRNA 200c plays an critical role in epithelial-mesenchymal transition (EMT) which enhance the migration and invasion of tumor cells and eventually lead to metastasis (Mongroo et al, 2010;Dykxhoorn 2010). Moreover, restoration of miRNA 200c to certain solid tumors showed the ability to increase the sensitivity to chemo drug or radiation by various mechanisms (Cochrane et al, 2009;Cittelly et al, 2012;Kopp et al, 2012;Chang et al, 2013;Shi et al, 2013 …”

Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

“…The emerging field of the role of micro RNAs in the mechanisms of the CSC-TPC state and the EMT is not considered as such in this review (Shi et al, 2010). See recent specific articles (Gunaratne, 2009;Kong et al, 2010;Mongroo and Rustgi, 2010;Castilla et al, 2011;Tellez et al, 2011).…”