Inhibition of miR-141 and miR-200a Increase DLC-1 and ZEB2 Expression, Enhance Migration and Invasion in Metastatic Serous Ovarian Cancer

Int J Environ Res Public Health. 2020 Apr 17;17(8):2766. doi: 10.3390/ijerph17082766.

Abstract

The role of microRNA (miRNA) in ovarian cancer has been extensively studied as a regulator for its targeted genes. However, its specific role in metastatic serous ovarian cancer (SOC) is yet to be explored. This paper aims to investigate the differentially expressed miRNAs in metastatic SOC compared to normal. Locked nucleic acid PCR was performed to profile miRNA expression in 11 snap frozen metastatic SOC and 13 normal ovarian tissues. Functional analysis and regulation of their targeted genes were assessed in vitro. Forty-eight miRNAs were significantly differentially expressed in metastatic SOC as compared to normal. MiR-19a is a novel miRNA to be upregulated in metastatic SOC compared to normal. DLC1 is possibly regulated by miR-141 in SOC. MiR-141 inhibition led to significantly reduced cell viability. Cell migration and invasion were significantly increased following miRNA inhibition. This study showed the aberrantly expressed miRNAs in metastatic SOC and the roles of miRNAs in the regulation of their targeted genes and ovarian carcinogenesis.

Keywords: MIRN141 microRNA; MIRN200 microRNA; metastasis; microRNA; serous ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial* / metabolism
  • Carcinoma, Ovarian Epithelial* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cystadenocarcinoma, Serous* / metabolism
  • Cystadenocarcinoma, Serous* / pathology
  • Female
  • GTPase-Activating Proteins* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / metabolism
  • Middle Aged
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Tumor Suppressor Proteins* / metabolism
  • Zinc Finger E-box Binding Homeobox 2* / metabolism

Substances

  • DLC1 protein, human
  • GTPase-Activating Proteins
  • MIRN141 microRNA, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Proteins
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2