Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression

Mol Cancer Ther. 2014 Dec;13(12):3086-97. doi: 10.1158/1535-7163.MCT-14-0245. Epub 2014 Sep 23.

Abstract

PTENP1 is a pseudogene of the PTEN tumor suppression gene (TSG). The functions of PTENP1 in clear-cell renal cell carcinoma (ccRCC) have not yet been studied. We found that PTENP1 is downregulated in ccRCC tissues and cells due to methylation. PTENP1 and PTEN are direct targets of miRNA miR21 and their expression is suppressed by miR21 in ccRCC cell lines. miR21 expression promotes ccRCC cell proliferation, migration, invasion in vitro, and tumor growth and metastasis in vivo. Overexpression of PTENP1 in cells expressing miR21 reduces cell proliferation, invasion, tumor growth, and metastasis, recapitulating the phenotypes induced by PTEN expression. Overexpression of PTENP1 in ccRCC cells sensitizes these cells to cisplatin and gemcitabine treatments in vitro and in vivo. In clinical samples, the expression of PTENP1 and PTEN is correlated, and both expressions are inversely correlated with miR21 expression. Patients with ccRCC with no PTENP1 expression have a lower survival rate. These results suggest that PTENP1 functions as a competing endogenous RNA (ceRNA) in ccRCC to suppress cancer progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Disease Progression
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology*
  • MicroRNAs / genetics
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics*
  • Prognosis
  • Pseudogenes*
  • RNA Interference
  • RNA, Messenger / genetics
  • Tumor Burden / genetics

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Deoxycytidine
  • gemcitabine
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Cisplatin