Long Non-Coding MALAT1 Functions as a Competing Endogenous RNA to Regulate Vimentin Expression by Sponging miR-30a-5p in Hepatocellular Carcinoma

Cell Physiol Biochem. 2018;50(1):108-120. doi: 10.1159/000493962. Epub 2018 Oct 2.

Abstract

Background/aims: Hepatocellular carcinoma (HCC) has a high morbidity as well as mortality and is believed to be one of the most prevalent cancers worldwide. The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in numerous cancers, including HCC. This study aimed to explore the role of MALAT1 in HCC progression.

Methods: The expression levels of MALAT1 and Vimentin in HCC tissues and relative pair-matched adjacent normal liver tissues were analyzed by RT-PCR, and immunohistochemistry. Using bioinformatics analysis and dual-luciferase assay, we examined the correlation between MALAT1 and miR-30a-5p. Dual-luciferase assay and western blotting suggested that Vimentin was a target of miR-30a-5p. A wound healing assay and transwell assays were employed to determine the effect of MALAT1 and miR-30a-5p on cell migration and invasion in HCC.

Results: Our data demonstrated that the levels of MALAT1 and Vimentin were upregulated in HCC tissues and that miR-30a-5p was a direct target of MALAT1. Silenced MALAT1 and overexpressed miR-30a-5p each inhibited cell migration and invasion. Additionally, dual-luciferase assay and western blotting demonstrated that MALAT1 could competitively sponge miR-30a-5p and thereby regulate Vimentin.

Conclusion: Our data suggest that MALAT1 acts as an oncogenic lncRNA that promotes HCC migration and invasion. Therefore, the MALAT1-miR-30a-5p-Vimentin axis is a potential therapeutic target and molecular biomarker in HCC.

Keywords: Hepatocellular carcinoma; MALAT1; Vimentin; miR-30a-5p.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antagomirs / metabolism
  • Base Sequence
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use
  • Sequence Alignment
  • Vimentin / chemistry
  • Vimentin / genetics
  • Vimentin / metabolism*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MALAT1 long non-coding RNA, human
  • MIRN30b microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Vimentin