Up-regulation of miR-20a by HPV16 E6 exerts growth-promoting effects by targeting PDCD6 in cervical carcinoma cells

Biomed Pharmacother. 2018 Jun:102:996-1002. doi: 10.1016/j.biopha.2018.03.154. Epub 2018 Apr 5.

Abstract

Objective: MicroRNAs (miRNAs/miRs) have been reported to participate in progression of multiple tumors including cervical cancer. High-risk human papillomavirus (HPV) type 16 (HPV16) is the most common and lethal HPV type, leading to exceeding 50% of cervical cancer cases. However, the relationship between miRNA and HPV-induced cervical carcinogenesis remains elusive.

Results: Here, HPV16 E6 positively regulated miR-20a expression. Overexpression of miR-20a showed growth-promoting effects on C33A cells (HPV16-negative), and knockdown of miR-20a showed growth-inhibitory effects on CaSki cells (HPV16-positive). In addition, PDCD6 was identified as a target gene of miR-20a. Overexpression of PDCD6 exerted growth-inhibitory effects (opposite to miR-20a overexpression), which could be reversed by miR-20a overexpression. More importantly, activation of AKT and p38 was observed in C33A cells overexpressing miR-20a, and the growth-promoting action of miR-20a could be abated by p38 inhibition.

Conclusion: Up-regulation of miR-20a by HPV16 E6 exerted growth-promoting effects by targeting PDCD6 in cervical carcinoma cells. This study demonstrated miR-20a might be a potential therapeutic target in HPV16 E6 infection type of cervical cancer.

Keywords: AKT/p38; Cervical cancer; HPV16; PDCD6; miR-20a.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Base Sequence
  • Calcium-Binding Proteins / metabolism*
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oncogene Proteins, Viral / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Up-Regulation / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • MIRN20a microRNA, human
  • MicroRNAs
  • Oncogene Proteins, Viral
  • PDCD6 protein, human
  • Repressor Proteins
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases