miR-133b inhibits cell proliferation, migration, and invasion of lung adenocarcinoma by targeting CDCA8

Pathol Res Pract. 2021 Jul:223:153459. doi: 10.1016/j.prp.2021.153459. Epub 2021 Apr 28.

Abstract

Objective: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. This study aims to explore the mechanism by which CDCA8 regulates cell proliferation, invasion, and migration of LUAD, and to generate novel insights into targeted therapy of LUAD.

Methods: Expression profiles of mature microRNAs (miRNAs) and mRNAs, along with clinical data of LUAD were downloaded from TCGA database for differential analysis and survival analysis to mine differentially expressed mRNAs. qRT-PCR was used to detect the expression of CDCA8 and miR-133b in LUAD cell lines, and western blot was used to detect protein expression. The effects of CDCA8 on the proliferation, migration, and invasion of LUAD cells were detected by CCK-8 assay, scratch healing assay, and Transwell assay. Bioinformatics predicted the target miRNA of CDCA8, and dual-luciferase reporter gene assay was used to verify the binding relationship between miR-133b and CDCA8.

Results: Data from TCGA-LUAD showed that CDCA8 was significantly overexpressed in LUAD tissue, while its upstream miRNA (miR-133b) was significantly lowly expressed. The result of dual-luciferase test showed that miR-133b targeted CDCA8. The results of in vitro functional experiments showed that overexpression of CDCA8 could promote the proliferation, invasion, and migration of LUAD cells, and miR-133b could reverse this promotion by targeting CDCA8.

Conclusion: This study found that CDCA8 was a carcinogenic factor in LUAD cells and it was regulated by upstream miR-133b. miR-133b could inhibit proliferation, invasion, and migration of LUAD cells by targeting CDCA8.

Keywords: CDCA8; Invasion; Migration; Proliferation; miR-133b.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Signal Transduction
  • Transcriptome

Substances

  • CDCA8 protein, human
  • Cell Cycle Proteins
  • MIRN133 microRNA, human
  • MicroRNAs