MicroRNA-505-5p functions as a tumor suppressor by targeting cyclin-dependent kinase 5 in cervical cancer

Biosci Rep. 2019 Jul 25;39(7):BSR20191221. doi: 10.1042/BSR20191221. Print 2019 Jul 31.

Abstract

MicroRNAs (miRs) are considered to be tumor suppressors or oncogenes as they regulate cell proliferation, migration, invasion, and differentiation. Recently, microRNA-505 (miR-505) has been reported as being involved in the progression of several human cancers. In the present study, we aim to investigate the expression rate and functional role of miR-505-5p in cervical cancer (CC) to determine its significance regarding the disease's development.The expression of miR-505-5p and cyclin-dependent kinase 5 (CDK5) in specimens of patients with CC and CC cell lines was examined by quantitative real-time PCR (qRT-PCR) and Western Blot. The relationship between miR-505-5p and CDK5 was verified by luciferase reporter assay. Cell counting kit-8 (CCK-8) assay, Scratch wound healing assay and transwell assay were used to detect the roles of miR-505-5p and CDK5 in CC cell functions. Western Blot was utilized to explore the epithelial-mesenchymal transition (EMT) markers.The result showed that in CC tissues and CC cell lines miR-505-5p was down-regulated while CDK5 level was up-regulated. MiR-505-5p was closely correlated with the metastasis-associated clinicopathological features. Overexpression of miR-505-5p inhibited cell viability, cell metastasis and EMT in CC cells. CDK5 was confirmed as a direct target of miR-505-5p and inverse relationship between them was also observed. Overexpression of CDK5 reduces the inhibitory effects of miR-505-5p in CC.Taken together, these results determine that miR-505-5p is a tumor suppressor miRNA which regulates tumor cell proliferation, migration, and invasion via binding to the functional target CDK5 and demonstrates its potential for future use in the treatment of CC.

Keywords: CDK5; Cervical cancer; cell invasion; cell migration; cell proliferation; miR-505-5p.

Publication types

  • Retracted Publication

MeSH terms

  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 5 / biosynthesis*
  • Cyclin-Dependent Kinase 5 / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN505 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Cyclin-Dependent Kinase 5
  • CDK5 protein, human