The lncRNA TP73-AS1 promotes ovarian cancer cell proliferation and metastasis via modulation of MMP2 and MMP9

J Cell Biochem. 2018 Sep;119(9):7790-7799. doi: 10.1002/jcb.27158. Epub 2018 Jun 15.

Abstract

Ovarian cancer is one of the most common gynecologic malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators in cancer development. The current study investigated the role of lncRNA P73 antisense RNA 1T (TP73-AS1) in ovarian cancer. Quantitative real-time polymerase chain reaction determined the expression levels of TP-73AS1, matrix metallopeptidases (MMPs) messenger RNA. Cell proliferative ability, cell invasion, and migration were CCK-8 and colony formation, and transwell invasion and migration assays, respectively. The protein levels of matrix metallopeptidase 2 (MMP2) and MMP9 were measured by Western blot. TP73-AS1 was upregulated in the ovarian cancer tissues and ovarian cancer cells, and upregulation of TP73-AS1 was associated with poor prognosis. Knockdown of TP73-AS1 significantly suppressed cell proliferation, invasion, and migration of SKOV3 cells, and overexpression of TP73-AS1 promoted cell proliferation, invasion, and migration of OVCA429 cells. In addition, knockdown of TP73-AS1 suppressed the in vivo tumor growth. Tumor metastasis RT2 profiler polymerase chain reaction array showed that MMP2 and MMP9 was significantly upregulated by TP73-AS1 overexpression in ovarian cancer cells. TP73-AS1 overexpression enhanced the expression of MMP2 and MMP9 in ovarian cancer cells. Knockdown of MMP2 and MMP9 attenuated the effects of TP73-AS1 overexpression on cell invasion and migration. The clinical data showed that MMP2 and MMP9 were upregulated and positively correlated with TP73-AS1 expression in ovarian cancer tissues. Collectively, our results demonstrated the oncogenic role of TP73-AS1 in ovarian cancer, and targeting TP73-AS1 may represent a novel approach in battling against ovarian cancer.

Keywords: MMP2; MMP9; TP73-AS1; long noncoding RNA; ovarian cancer; proliferation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Survival Analysis
  • Up-Regulation*

Substances

  • RNA, Long Noncoding
  • long non-coding RNA KIAA0495, human
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9