miR-381 Inhibits Proliferation and Invasion of Non-Small-Cell Cancer Cells by Targeting USP39

Dis Markers. 2022 Aug 21:2022:2195393. doi: 10.1155/2022/2195393. eCollection 2022.

Abstract

It is known that miR-381 plays a therapeutic role in a variety of cancers, but the regulatory mechanism of miR-381 in the treatment of lung cancer remains unclear. This study is aimed at exploring the expression level and mechanism of miR-381 in lung cancer. In this experiment, quantitative real-time PCR (qRT-PCR), western blot, and other methods were used to detect the expression of miR-381 and ubiquitin-specific protease 39 (USP39) in lung cancer tissues. The target genes of miR-381 were predicted by bioinformatics techniques, and the targeting relationship between miR-381 and USP39 was verified by the dual-luciferase reporting method. The expression levels of miR-381 and USP39 were adjusted to verify the effect of miR-381 on the expression of USP39 gene. The effect of miR-381 expression on proliferation of lung cancer cells was verified by cell proliferation and invasion experiments. miR-381 was downregulated in non-small-cell lung cancer tissues and cell lines, while USP39 was upregulated. The dual-luciferase reporter gene assay showed that miR-381 and USP39 had targeted binding sites. After transfection with miR-381 mimics, USP39 expression was significantly decreased, cell proliferation decreased, and apoptosis increased. After transfection with miR-381 inhibitor, USP39 expression was significantly increased, cell proliferation increased, and cell apoptosis decreased. Overexpression of USP39 significantly increased the invasion ability and cell survival curve (p < 0.05). In conclusion, overexpression of miR-381 can regulate the expression of USP39, inhibit the proliferation and invasion of cancer cells, and induce apoptosis of cancer cells. This may provide a new perspective and strategy for targeted therapy of non-small-cell lung cancer.

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Invasiveness / genetics
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism

Substances

  • MIRN381 microRNA, human
  • MicroRNAs
  • Luciferases
  • USP39 protein, human
  • Ubiquitin-Specific Proteases