Regulating BMI1 expression via miRNAs promote Mesenchymal to Epithelial Transition

• Published in: PloS one Vol. 13; no. 2; p. e0190245
• Main Authors: Patel, Nibedita, Garikapati, Koteswara Rao, Makani, Venkata Krishna Kanth, Nair, Ayikkara Drishya, Vangara, Namratha, Bhadra, Utpal, Pal Bhadra, Manika
• Format: Journal Article
• Language: English
• Published: Public Library of Science 02-02-2018
• Subjects: Breast cancer; Gene expression; Genetic aspects; Genetic transcription; Metastasis; MicroRNA; Physiological aspects; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0190245

Polycomb group (PcG) proteinB lymphoma Mo-MLV insertion region 1 homolog (BMI1) is a transcriptional repressor that plays an important role in human carcinogenesis. MicroRNAs (miRNAs) are endogenous small non-coding RNAsthat implicate a negative regulation on gene expression. Deregulation of the expression of miRNAs has been implicated in tumorigenesis. Here, we have shown that knock-down ofBMI1increases theexpression of tumor-suppressivemiRNAs. Elevated levels of expression of miR-200a, miR-200b, miR-15a, miR-429, miR-203were observed upon knock-down of BMI1. Up-regulation of these miRNAsleads to down-regulation ofPRC1 group of proteins i.e. BMI1, RING1A, RING1B and Ub-H2A. Interestingly, overexpression of miR-200a, miR-200b and miR-15aalso produced decreased BMI1 and Ub-H2A protein expression in the CD44+ Cancer Stem Cellpopulation of MDAMB-231cells. Also,elevating the levels of BMI1 regulated miRNAspromoted Mesenchymal to Epithelial transition by regulating the expression of N-Cadherin, Vimentin, [beta]-Catenin, Zeb, Snail thereby resulting in decreased invasion, migration and proliferation. Here, we also report that miR-200a, miR-200b, miR-203 accretes the sensitivity of MDAMB-231 cells to the histone deacetylase inhibitor (HDACi) SAHA and miR-15a sensitized breast cancer cells to the chemotherapeutic drug cisplatin leading to apoptosis. These findings suggest that modulatingspecific miRNAs may serve as a therapeutic approach for the treatment of breast cancer