MiR-17-5p promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p21

Cancer Med. 2016 Dec;5(12):3489-3499. doi: 10.1002/cam4.863. Epub 2016 Oct 24.

Abstract

MicroRNAs (miRNAs) may act as either tumor suppressors or oncogenes in various types of cancers. Previous studies have indicated that miR-17-5p is involved in the initiation and development of human tumors. However, its mechanism and function in nasopharyngeal carcinoma (NPC) remain largely unclear. In this study, we evaluated the expression profiles of miR-17-5p and p21 in NPC cell lines and tissues by quantitative real-time PCR (qRT-PCR). For the analysis, we have established a stable overexpression or depletion of miR-17-5p NPC cell lines for analyzing the effects of cell proliferation by MTT, colony formation, and cell cycle assay. A nude mice xenograft model was used to verify the tumor growth in vivo. MiR-17-5p was overexpressed, whereas the expression of p21 was downregulated in NPC cell lines and tissues. The miR-17-5p expression level was inversely correlated with the p21 mRNA level in NPC samples. Furthermore, analysis of 2-ΔΔCt value in 81 NPC patients suggested that the elevated expression level of miR-17-5p or the downregulated expression level of p21 was significantly correlated with tumor size (T classification) and tumor stage, and Kaplan-Meier survival analysis revealed a correlation between miR-17-5p or p21 expression level and overall survival times in 81 NPC patients. MiR-17-5p promoted cell growth in vivo and in vitro by directly targeting p21. Our results indicate that miR-17-5p can promote the occurrence of NPC and it may serve as a potential novel diagnostic maker or therapeutic target for NPC in the future.

Keywords: Cell proliferation; miR-17-5p; nasopharyngeal carcinoma; p21; poor prognosis.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • RNA Interference*
  • Retinoblastoma Protein / metabolism
  • Signal Transduction
  • Xenograft Model Antitumor Assays
  • p21-Activated Kinases / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN17 microRNA, human
  • MicroRNAs
  • Retinoblastoma Protein
  • p21-Activated Kinases