The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway

Mol Carcinog. 2018 Feb;57(2):225-234. doi: 10.1002/mc.22749. Epub 2017 Nov 6.

Abstract

As one of the most frequently diagnosed cancers in women, the development and progression of epithelial ovarian carcinoma (EOC) remains an open area of research. The role of long non-coding RNAs (lncRNAs) in EOC is an emerging field of study. We found that LncRNA TDRG1 (human testis development-related gene 1) was highly expressed in EOC tissues than in normal ovarian tissues, and expression differed significantly with differentiation. LncRNA TDRG1 downregulation suppressed EOC cell proliferation, migration, and invasion, while its overexpression had the opposite effect. Bioinformatic predictions and dual-luciferase reporter assays showed that LncRNA TDRG1 has possible miRNA-93 (miR-93) binding sites. LncRNA TDRG1 downregulation upregulated miR-93 expression, while its overexpression reduced miR-93 expression. In addition, TDRG1 downregulation reduced the expression of Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6 K), Bcl-xL, and matrix metalloproteinase 2 (MMP2) protein, which are regulated by miR-93, while its upregulation induced RhoC, P70S6 K, Bcl-xL, and MMP2 protein expression. In vivo, LncRNA TDRG1 overexpression induced tumor development and RhoC expression. Taken together, our results demonstrated for the first time that LncRNA TDRG1 may be a new and important diagnostic and therapeutic target in EOC.

Keywords: epithelial ovarian carcinoma; lncRNA TDRG1; progression miR-93; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma, Ovarian Epithelial
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • MicroRNAs / genetics*
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Proteins / genetics*
  • RNA, Long Noncoding
  • Signal Transduction / genetics*
  • Up-Regulation / genetics
  • rhoC GTP-Binding Protein / genetics*

Substances

  • MIRN93 microRNA, human
  • MicroRNAs
  • Proteins
  • RNA, Long Noncoding
  • TDRG1 long non-coding RNA, human
  • Matrix Metalloproteinase 2
  • RHOC protein, human
  • rhoC GTP-Binding Protein