Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 regulates the expression of Gli2 by miR-202 to strengthen gastric cancer progression

Biomed Pharmacother. 2017 Jan;85:264-271. doi: 10.1016/j.biopha.2016.11.014. Epub 2016 Nov 22.

Abstract

Background: Gastric cancer (GC) is one of the most common malignancies and ranks the second leading cause of cancer death worldwide. Some studies had reported the tumor-promoting effects of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a competing endogenous RNA (ceRNA) by sponging to microRNAs. However, the molecular mechanism of ceRNA regulatory pathway involving MALAT1 in GC remains unclear.

Methods: MALAT1 and miR -202 expression was detected by quantitative real time PCR (qRT-PCR) in 60 gastric cancer tissues and adjacent normal tissues, CCK8 cell proliferation assays, cell cycle analysis and cell apoptosis assays were performed to detect the GC cell proliferation and apoptosis. The mRNA and protein levels of Gli2 were analyzed by quantitative real-time PCR and Western blotting assays. Furthermore, using online software, luciferase reporter assays, RNA immunoprecipitation (RIP) and RNA pulldown assays demonstrated miR-202 was a target of MALAT1.

Results: We found that MALAT1 was upregulated in GC tissues and higher MALAT1 expression was correlated with larger tumor size, lymph node metastasis, and TNM stage. Moreover, we revealed that MALAT1 was a direct target of miR-202 and knockdown of MALAT1 significantly decreased the expression of Gli2 through negatively regulating miR-202. In addition, knockdown of Malat1 inhibited GC cells proliferation, S-phase cell number, and induced cell apoptosis via negatively regulating miR-202 in vitro.

Conclusions: Our results elucidated MALAT1/miR-202/Gli2 regulatory pathway, which maybe contribute to a novel therapeutic strategy for GC patients.

Keywords: Competing endogenous RNA; Gastric cancer; Gli2; Metastasis-associated lung adenocarcinoma transcript 1; miR-202.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • S Phase Cell Cycle Checkpoints
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Time Factors
  • Transcription, Genetic*
  • Transfection
  • Tumor Burden
  • Up-Regulation
  • Zinc Finger Protein Gli2

Substances

  • GLI2 protein, human
  • Kruppel-Like Transcription Factors
  • MALAT1 long non-coding RNA, human
  • MIRN202 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • Zinc Finger Protein Gli2