MicroRNA-142-3p/MALAT1 inhibits lung cancer progression through repressing β-catenin expression

Biomed Pharmacother. 2019 Jun:114:108847. doi: 10.1016/j.biopha.2019.108847. Epub 2019 Apr 7.

Abstract

MALAT1 is well documented to be highly expressed in non-small cell lung cancer (NSCLC) and its overexpression closely associates the malignant phenotype of NSCLC cells and poor prognosis of NSCLC patients. MALAT1 is also identified to enhance β-catenin expression and under the negative regulation of miR-142-3p. However, the role of miR-142-3p/MALAT1/β-catenin in the occurrence and development of NSCLC remains unclear. The objective of this study was to explore it. The results showed that miR-142-3p expression was reduced in NSCLC tissues, while β-catenin and MALAT1 expression levels were elevated. MTT, transwell chamber, flow cytometry assays demonstrated that up-regulation of miR-142-3p with mimic transfection significantly inhibited the proliferation, migration and promoted the apoptosis of NSCLC H1299 cells, and induced a G0/G1 phase arrest and S phase reduction. Besides, miR-142-3p negatively decreased MALAT1 expression as detected by RT-PCR and luciferase reporter assays. Moreover, up-regulation of miR-142-3p decreased β-catenin expression through down-regulating MALAT1 in H1299 cells. And in vivo experiment showed that miR-142-3p up-regulation, as well as the knockdown of either β-catenin or MALAT1 significantly reduced the tumorigenesis of NSCLC cells. Taken together, our study makes clear that miR-142-3p functions as a tumor suppressor in NSCLC progression through inhibiting MALAT1/β-catenin signaling.

Keywords: MALAT1; Non-small cell lung cancer; miR-142-3p; β-catenin.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor / physiology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Up-Regulation / genetics
  • beta Catenin / genetics*

Substances

  • CTNNB1 protein, human
  • MALAT1 long non-coding RNA, human
  • MIRN142 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • beta Catenin