The role of long non-coding RNA PCA3 in epithelial ovarian carcinoma tumorigenesis and progression

Gene. 2017 Oct 30;633:42-47. doi: 10.1016/j.gene.2017.08.027. Epub 2017 Aug 31.

Abstract

Objectives: Ovarian carcinoma is one of the highest incidence of tumors in women, and the generation, development and prognosis of epithelial ovarian carcinoma (EOC) remains an open field of study. The role of long non-coding RNAs (lncRNAs) in epithelial ovarian carcinoma is an emerging area of research.

Materials and methods: LncRNA PCA3 expression was determined in EOC and normal ovarian tissues by RT-PCR. Phenotypes indicative of tumor progression and aggressiveness, including cell proliferation, migration, invasion, and expression of related molecules, were analysed in EOC cell following knockdown of lncRNA PCA3 by transfection with small interfering RNA (siRNA).

Results: Expression of lncRNA PCA3 in epithelial ovarian cancer tissues was higher than in normal ovarian tissue. We discovered that knockdown of lncRNA PCA3 in EOC cells by siRNA transfection significantly suppressed cell proliferation, migration, and invasion. Bioinformatic predictions and dual-luciferase reporter assays indicate that the 3'UTR of PCA3 has potential binding sites for miR-106b-5p. Knockdown of the lncRNA PCA3 by siRNA resulted in up-regulated miR-106b expression. In addition, knockdown of PCA3 also reduced protein expression of Ras homolog gene family member C (RhoC), Bcl/xl, P70 ribosomal S6 kinase (P70S6K), and Matrix metallopeptidase 2 (MMP2), which are regulated by miR-106b.

Conclusions: Research results show that lncRNA PCA3 may coordinate EOC tumorigenesis through disrupting miR-106b regulated gene expression. PCA3 may be a novel and important diagnostic biomarker and a valuable marker for prediction in the clinical care of epithelial ovarian carcinoma.

Keywords: Epithelial ovarian carcinoma; LncRNA; PCA3; Progression; Tumorigenesis.

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • RNA, Small Interfering
  • Up-Regulation

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • MIRN106 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • prostate cancer antigen 3, human