Integrative analysis of miRNAs-mRNAs reveals that miR-182 up-regulation contributes to proliferation and invasion of nasopharyngeal carcinoma by targeting PTEN

Aging (Albany NY). 2020 Jun 15;12(12):11568-11578. doi: 10.18632/aging.103316. Epub 2020 Jun 15.

Abstract

Objective: Several miRNAs have been found to be abnormally expressed during nasopharyngeal carcinoma development. Nevertheless, the interaction between miRNAs and downstream genes remains unexploited. In this study, we aim to investigate miRNAs-mRNAs interaction and the mechanism of miR-182 in NPC.

Results: Integrative analysis identified several hub-miRNAs that drive NPC pathogenesis. The expression of miR-182 was notably increased in 32 NPC tissues and cell lines (CNE1 and 5-8F). Up-regulation of miR-182 was strongly correlated with poor prognosis of NPC patients. Moreover, the proliferation and invasion of NPC cells were notably increased in miR-182 mimics condition and decreased in miR-182 inhibitor condition. Furthermore, PTEN was verified to be a target of miR-182 and overexpression of PTEN could abrogate the promotion effect of miR-182 mimics on NPC invasion.

Conclusions: We identified several hub-miRNAs that may drive NPC pathogenesis. MiR-182 could promote proliferation and invasion of NPC cells via targeting PTEN, which provides a new insight into the clinical therapy of NPC.

Materials and methods: Genome-wide miRNAs of NPC tissues was analyzed using high-throughput sequencing and bioinformatics tools. QRT-PCR experiment was conducted to measure relative expression level. Dual-luciferase reporter assay was used to verify target relationship. The proliferation and invasion of transfected cells were measured by CCK-8 and transwell assay.

Keywords: PTEN; invasion; miR-182; nasopharyngeal carcinoma; proliferation.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharynx / pathology
  • Neoplasm Invasiveness / genetics
  • PTEN Phosphohydrolase / genetics*
  • RNA, Messenger / metabolism
  • Up-Regulation

Substances

  • MicroRNAs
  • Mirn182 microRNA, human
  • RNA, Messenger
  • PTEN Phosphohydrolase
  • PTEN protein, human