LncRNA PCGEM1 Induces Ovarian Carcinoma Tumorigenesis and Progression Through RhoA Pathway

Cell Physiol Biochem. 2018;47(4):1578-1588. doi: 10.1159/000490931. Epub 2018 Jun 27.

Abstract

Background/aims: Prostate cancer gene expression marker 1 (PCGEM1) is a long noncoding RNA (lncRNA) and is well known as a promoter in prostate cancer and osteoarthritis synoviocytes. However, the role PCGEM1 plays in epithelial ovarian cancer is unknown.

Methods: PCGEM1 expression was examined in epithelial ovarian cancer and normal ovarian tissues using reverse transcription-PCR. Ovarian cancer cell phenotypes and genotypes were examined after PCGEM1 overexpression or downregulation in vitro; besides, the effects of PCGEM1 overexpression was also examined in vivo.

Results: PCGEM1 expression level was higher in epithelial ovarian cancer tissues than in normal ovarian tissues and was positively associated with differentiation (Well vs. Mod/Poor). Upregulation of PCGEM1 induced cancer cell proliferation, migration, and invasion, but decreased cell apoptosis through upregulating RhoA, YAP (Yes-associated protein), MMP2 (matrix metalloproteinase 2), Bcl-xL, and P70S6K expression; while PCGEM1 downregulation had the opposite effect. The nude mouse xenograft assay demonstrated that PCGEM1 overexpression promoted tumor growth. Furthermore, silencing RhoA expression reversed the effect of PCGEM1 and significantly inhibited RhoA, YAP, MMP2, Bcl-xL, and P70S6K protein expression.

Conclusion: In conclusion, we suggest that PCGEM1 may be an inducer in epithelial ovarian cancer tumorigenesis and progression by upregulating RhoA and the subsequent expression of YAP, P70S6K, MMP2, and Bcl-xL.

Keywords: Lncrna PCGEM1; Ovarian cancer; RhoA; Tumorigenesis and progression.

MeSH terms

  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Long Noncoding / metabolism*
  • RNA, Neoplasm / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Neoplasm Proteins
  • PCGEM1 non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • RHOA protein, human
  • rhoA GTP-Binding Protein