Long non-coding RNA MALAT1 regulates proliferation, apoptosis, migration and invasion via miR-374b-5p/SRSF7 axis in non-small cell lung cancer

Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1853-1862. doi: 10.26355/eurrev_202002_20363.

Abstract

Objective: Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported to play a tumor-promoting role in NSCLC; however, the regulatory mechanism of MALAT1 in NSCLC progression remains largely unknown.

Materials and methods: The expression levels of MALAT1, miR-374b-5p and SRSF7 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein level of SRSF7 was detected by Western blot analysis. Cell proliferation and apoptosis were determined by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, starBase3.0 software and dual-luciferase reporter assay were used to identify the correlations between miR-374b-5p and MALAT1 or SRSF7. Nude mouse xenograft assay was performed to explore the effects of MALAT1 on NSCLC in vivo.

Results: We first observed that the levels of MALAT1 and SRSF7 were upregulated while miR-374b-5p was downregulated in NSCLC tissues; meanwhile, the expression level of MALAT1 was negatively correlated with miR-374b-5p and positively correlated with SRSF7. Both knockdown of MALAT1 and miR-374b-5p overexpression inhibited proliferation, migration and invasion and induced apoptosis in NSCLC cells. Then, we identified that miR-374b-5p was a target of MALAT1 and SRSF7 was the downstream of miR-374b-5p. In addition, overexpression of SRSF7 reversed the effects of MALAT1 knockdown on proliferation, apoptosis, migration and invasion in NSCLC cells. Finally, overexpression of MALAT1 suppressed NSCLC tumor growth in vivo.

Conclusions: Our results demonstrated that MALAT1 contributed to NSCLC progression through the MALAT1/miR-374b-5p/SRSF7 axis.

MeSH terms

  • Apoptosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Serine-Arginine Splicing Factors / genetics
  • Serine-Arginine Splicing Factors / metabolism*

Substances

  • MALAT1 long non-coding RNA, human
  • MIRN374 microRNA 374, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SRSF7 protein, human
  • Serine-Arginine Splicing Factors