MiR-29a inhibits cell proliferation and migration by targeting the CDC42/PAK1 signaling pathway in cervical cancer

Anticancer Drugs. 2019 Jul;30(6):579-587. doi: 10.1097/CAD.0000000000000743.

Abstract

Cervical cancer is the second most common gynecological malignancy worldwide and the tumorigenesis mechanisms of cervical cancer are still unclear. This study aimed to reveal the role of miR-29a in cervical cancer. The expression level of miR-29a and CDC42 was measured using qRT-PCR. Cell proliferation, apoptosis, migration, and invasion were detected using colony formation, flow cytometry analysis, wound-healing assay, and Transwell assay, respectively. Luciferase reporter assay was used to determine the binding of miR-29a with CDC42. CDC42/p21-activated kinase 1 (PAK1) pathway-related proteins were measured by western blotting. MiR-29a was downregulated and CDC42 was upregulated in cervical cancer cells. Luciferase reporter assay showed that miR-29a negatively regulated the expression of CDC42 by directly targeting 3'-UTR of CDC42. Cell proliferation, migration, and invasion were markedly inhibited, whereas cell apoptosis was significantly increased in Hela and CaSki cells transfected with miR-29a mimics. These effects were partly recovered by CDC42 overexpression. Protein levels of PAK1, p-PAK1, p-LIMK, and p-cofilin were significantly downregulated by miR-29a mimics, which was reversed by CDC42 overexpression and was increased by the miR-29a inhibitor. MiR-29a inhibited cell proliferation, migration, and invasion, as well as promoted cell apoptosis through repressing the PAK1/LIMK signaling pathway by targeting CDC42 in cervical cancer.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • MIRN29a microRNA, human
  • MicroRNAs
  • PAK1 protein, human
  • p21-Activated Kinases
  • CDC42 protein, human
  • cdc42 GTP-Binding Protein