MiRNA-144-5p down-modulates CDCA3 to regulate proliferation and apoptosis of lung adenocarcinoma cells

Mutat Res. 2022 Jul-Dec:825:111798. doi: 10.1016/j.mrfmmm.2022.111798. Epub 2022 Sep 1.

Abstract

Background: Lung adenocarcinoma (LUAD) belongs to non-small cell lung cancer. In addition to surgical resection, chemotherapy and radiotherapy cause great side effects and low 5-year survival rates. MiRNAs are closely related to cancer development. This study aimed to analyze the molecular mechanism of miRNA-144-5p targeting CDCA3 to inhibit LUAD proliferation.

Methods: MiRNA and mRNA data were downloaded from TCGA-LUAD dataset for differential expression analysis. TargetScan and miRTarBase databases were adopted to predict the target genes of miRNA, and the signaling pathways involved were analyzed by gene set enrichment analysis. The functions of LUAD cells were analyzed by CCK-8, colony formation assay, stem cell spheroidization assay, and flow cytometry. The expression levels of CDCA3, p53, and cell cycle-associated proteins were evaluated by Western blot.

Results: The expression of miRNA-144-5p was significantly down-regulated in LUAD, but overexpression of it repressed proliferation and spheroidization, and promoted apoptosis of LUAD cells. By bioinformatics prediction and dual-luciferase reporter assay, miRNA-144-5p was validated to target CDCA3, thereby regulating proliferation of LUAD cells. Besides, the results of cell experiments showed that miRNA-144-5p targeting CDCA3 affected cell proliferation and apoptosis in LUAD by regulating cell cycles, and miRNA-144-5p/CDCA3 mediated the p53 signaling pathway to affect the growth of LUAD cells.

Significance: Through the study of the pathogenesis of miRNA-144-5p regulating LUAD, we can better understand the molecular mechanism underlying LUAD development.

Keywords: Apoptosis; CDCA3; Lung adenocarcinoma; MiRNA-144–5p; P53; Proliferation.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung*
  • Cell Cycle Proteins
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Membrane Proteins
  • MicroRNAs* / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Tumor Suppressor Protein p53
  • MicroRNAs
  • Cell Cycle Proteins
  • Membrane Proteins
  • CDCA3 protein, human
  • MIRN144 microRNA, human