Regulating BMI1 expression via miRNAs promote Mesenchymal to Epithelial Transition (MET) and sensitizes breast cancer cell to chemotherapeutic drug

Abstract

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, β-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

Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for hepatocellular carcinoma

“…Undoubtedly, research related to tumorigenicity in terms of miRNA regulation is critically needed. miRNAs are RNA molecules of approximately 22 nucleotides in length that bind to the 3′-untranslated region (3′-UTR) of their respective target genes and exert their influence on gene expression by either inhibiting protein translation or degrading mRNA [35]. miRNAs are known to be an integral component of cancer development [35].…”

“…miRNAs are RNA molecules of approximately 22 nucleotides in length that bind to the 3′-untranslated region (3′-UTR) of their respective target genes and exert their influence on gene expression by either inhibiting protein translation or degrading mRNA [35]. miRNAs are known to be an integral component of cancer development [35]. We noted that the DEmiRNA hsa-miR-182 (connection degree = 13) had the highest connection degree among the prognostic DEmiRNAs (hsa-miR-182 and hsa-miR-183) in the ceRNA network, suggesting an obvious influence of hsa-miR-424 on HCC pathogenesis and prognosis (Additional file 5: Table S5).…”

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

“…miRNAs are known to be an integral component of cancer development [17][18][19]. Several studies have highlighted the role of miR-182-5p in the development of different cancers [13,14].…”

P4HB modulates epithelial‑mesenchymal transition and the β‑catenin/Snail pathway influencing chemoresistance in liver cancer cells

“…Epithelial integrity requires the stability of E-cadherin/β-catenin complexes (25). Previous studies have reported that Snail, β-catenin and EMT contribute to tumor chemotherapeutic resistance to sorafenib (26) and cisplatin (27)(28)(29).…”