MiR-495-3p and miR-143-3p co-target CDK1 to inhibit the development of cervical cancer

Clin Transl Oncol. 2021 Nov;23(11):2323-2334. doi: 10.1007/s12094-021-02687-6. Epub 2021 Aug 13.

Abstract

Purpose: The GEO database and KEGG database-based analyses identified the differential expression of cyclin-dependent kinase 1 (CDK1) in cervical cancer and its involvement in the cell cycle pathway. In the present study, we aim to clarify the role of CDK1 in cervical cancer and the function of upstream microRNA (miR)-143-3p/miR-495-3p.

Methods: The expression of miR-143-3p, miR-495-3p, and CDK1 in cervical cancer tissues and cells was determined using RT-qPCR. Cell bioactivities were examined by CCK-8 and flow cytometry. The binding affinity between CDK1 and miR-143-3p/miR-495-3p was investigated using dual luciferase gene reporter assay. A xenograft mouse model of cervical cancer was then established to explore their effect on the tumorigenicity of cervical cancer cells in vivo.

Results: CDK1 was found to be the common target gene of miR-143-3p and miR-495-3p. CDK1 overexpression occurred in cervical cancer tissues and cells, while expression of miR-495-3p and miR-143-3p was down-regulated. The viability was inhibited while the apoptosis was promoted in cervical cancer cells in response to miR-143-3p or miR-495-3p overexpression, or CDK1 silencing. Further, miR-143-3p or miR-495-3p overexpression was also substantiated to inhibit the tumorigenicity of cervical cancer cells in vivo, while CDK1 overexpression counteracted their effect.

Conclusion: Taken together, miR-143-3p and miR-495-3p co-target CDK1, thereby inhibiting the occurrence and development of cervical cancer.

Keywords: Apoptosis; CDK1; Cervical cancer; Proliferation; miR-143-3p; miR-495-3p.

MeSH terms

  • Animals
  • Apoptosis
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Cervix Uteri / metabolism
  • Databases, Genetic
  • Down-Regulation
  • Female
  • Gene Silencing
  • Genes, Reporter
  • HeLa Cells
  • Heterografts
  • Humans
  • Luciferases / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Random Allocation
  • Up-Regulation
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN143 microRNA, human
  • MIRN495 microRNA, human
  • MicroRNAs
  • Luciferases
  • CDC2 Protein Kinase
  • CDK1 protein, human