MicroRNA-30e-5p promotes cell growth by targeting PTPN13 and indicates poor survival and recurrence in lung adenocarcinoma

J Cell Mol Med. 2017 Nov;21(11):2852-2862. doi: 10.1111/jcmm.13198. Epub 2017 Jun 27.

Abstract

Aberrant microRNA expression is involved in the regulation of various cellular processes, such as proliferation and metastasis in multiple diseases including cancers. MicroRNA-30e-5p (miR-30e) was previously reported as an oncogenic or tumour suppressing miRNA in some malignancies, but its function in lung adenocarcinoma (LAC) remains largely undefined. In this study, we found that the expression of miR-30e was increased in LAC tissues and cell lines, associated with tumour size and represented an independent prognostic factor for overall survival and recurrence of LAC patients. Further functional experiments showed that knockdown of miR-30e suppressed cell growth while its overexpression promoted growth of LAC cells and xenografts in vitro and in vivo. Mechanistically, PTPN13 was identified as the direct target of miR-30e in LAC, in which PTPN13 expression was down-regulated in LAC tissues and showed the inverse correlation with miR-30e expression. Overexpression of PTPN13 inhibited cell growth and rescued the proliferation-promoting effect of miR-30e through inhibition of the EGFR signalling. Altogether, our findings suggest that miR-30e could function as an oncogene in LAC via targeting PTPN13 and act as a potential therapeutic target for treating LAC.

Keywords: PTPN13; growth; lung adenocarcinoma; microRNA-30e-5p.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma of Lung
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Male
  • Mice, Nude
  • MicroRNAs / agonists
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13 / metabolism
  • Signal Transduction
  • Survival Analysis
  • Xenograft Model Antitumor Assays

Substances

  • MIRN30b microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • Luciferases
  • EGFR protein, human
  • ErbB Receptors
  • PTPN13 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13