miR-34a-5p Inhibits Cell Proliferation, Migration and Invasion Through Targeting JAG1/Notch1 Pathway in HPV-Infected Human Epidermal Keratinocytes

Pathol Oncol Res. 2020 Jul;26(3):1851-1859. doi: 10.1007/s12253-019-00782-2. Epub 2019 Nov 28.

Abstract

Condyloma acuminate (CA) is a communicable disease caused by human papillomavirus (HPV). This study aimed to study the targeting relationship between miR-34a-5p and Jagged 1 (JAG1), as well as its regulatory effect in HPV-infected cells. Human keratinocyte HaCaT cells were infected with HPV16E6, and CA tissues were collected. The expression level of miR-34a-5p and JAG1 were detected in CA tissues and HPV-HaCaT cells. Cell proliferation, migration and invasion were respectively measured using 3-(4, 5)-dimethylthiahiazo-(-z-y1)-3, 5-diphenytetrazoliumromide (MTT), cell wound healing and Transwell assay. The potential binding sites of miR-34a-5p and JAG1 were predicted by website TargetScan, and confirmed using dual luciferase reporter gene assay. The proteins of Notch1 pathway-related were assessed using western blotting. The results showed that miR-34a-5p expression was decreased, and JAG1 expression was increased in CA tissues and HPV-HaCaT cells. Cell proliferation, migration and invasion were decreased when miR-34a-5p over-expression and JAG1 knock-down in HPV-HaCaT cells. Furthermore, miR-34a-5p had a targeting effect on JAG1. The expression level of Notch1, NICD, Hes1 and Hey1 were increased when miR-34a-5p knock-down. miR-34a-5p could inhibit cell development, and regulate the activity of Notch1 pathway through targeting JAG1 expression in HPV-infected keratinocytes.

Keywords: Condyloma acuminate (CA); Human papillomavirus (HPV); Jagged 1 (JAG1); Notch1 pathway; miR-34a-5p.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Condylomata Acuminata / metabolism
  • Condylomata Acuminata / pathology*
  • Condylomata Acuminata / virology
  • Female
  • Gene Expression Regulation / genetics
  • Humans
  • Jagged-1 Protein / metabolism*
  • Keratinocytes / metabolism
  • Keratinocytes / virology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology*
  • Receptor, Notch1 / metabolism*
  • Signal Transduction / physiology

Substances

  • JAG1 protein, human
  • Jagged-1 Protein
  • MIRN34 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Receptor, Notch1