Long non-coding RNA MINCR promotes gallbladder cancer progression through stimulating EZH2 expression

Cancer Lett. 2016 Sep 28;380(1):122-33. doi: 10.1016/j.canlet.2016.06.019. Epub 2016 Jun 23.

Abstract

The regulation of MYC-regulated long non-coding RNAs has been reported to contribute to certain types of cancers. However, the role of MYC-induced long non-coding RNA (MINCR) in the tumorigenesis of gallbladder cancer (GBC) is still largely unknown. In this study, we discovered that MINCR was markedly upregulated in GBC tissues compared with adjacent normal tissues. High MINCR expression levels in GBC were positively associated with tumor volume and lymph node metastasis and were negatively correlated with overall survival (OS). Upregulation of MINCR and enhancer of zeste homolog 2 (EZH2) in GBC coincided with the downregulation of miR-26a-5p in GBC. Mechanistically, MINCR/miR-26a-5p/EZH2 axis was found to be involved in cell proliferation, cell invasive and apoptosis in GBC cells. Moreover, knockdown of MINCR suppressed cell proliferation, decreased S-phase cell numbers, increased cell apoptosis, and inhibited cell invasion by inhibiting the epithelial-mesenchymal transition (EMT) phenomenon in GBC cells. In vivo, tumor volumes were significantly decreased in the MINCR silencing group compared with those in the control group. These results demonstrated that MINCR could potentially be a therapeutic target as well as a prognostic marker in GBC.

Keywords: Competing endogenous RNA; Enhancer of zeste homolog 2; Gallbladder cancer; MYC-induced long non-coding RNA; miR-26a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epithelial-Mesenchymal Transition
  • Gallbladder Neoplasms / genetics
  • Gallbladder Neoplasms / metabolism*
  • Gallbladder Neoplasms / mortality
  • Gallbladder Neoplasms / surgery
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation

Substances

  • MIRN26A microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA MINCR, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein