The lncRNA MALAT1 functions as a competing endogenous RNA to regulate MCL-1 expression by sponging miR-363-3p in gallbladder cancer

J Cell Mol Med. 2016 Dec;20(12):2299-2308. doi: 10.1111/jcmm.12920. Epub 2016 Jul 15.


Gallbladder carcinoma (GBC) is an aggressive neoplasm, and the treatment options for advanced GBC are limited. Recently, long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several cancers. In this study, we found that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was up-regulated in GBC tissues (P < 0.05). Luciferase reporter assays and RNA pull down assays showed that MALAT1 is a target of miR-363-3p. Real-time quantitative PCR and Western blot analysis indicated that MALAT1 regulated Myeloid cell leukaemia-1 (MCL-1) expression as a competing endogenous RNA (ceRNA) for miR-363-3p in GBC cells. Furthermore, MALAT1 silencing decreased GBC cell proliferation and the S phase cell population and induced apoptosis in vitro. In vivo, tumour volumes were significantly decreased in the MALAT1 silencing group compared with those in the control group. These data demonstrated that the MALAT1/miR-363-3p/MCL-1 regulatory pathway controls the progression of GBC. Inhibition of MALAT1 expression may be to a novel therapeutic strategy for gallbladder cancer.

Keywords: MALAT1; MCL-1; competing endogenous RNA; gallbladder cancer; miR-363-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics*
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tumor Burden / genetics


  • MALAT1 long non-coding RNA, human
  • MCL1 protein, human
  • MIRN363 microRNA, human
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • RNA, Long Noncoding