MiR-122 inhibits epithelial mesenchymal transition by regulating P4HA1 in ovarian cancer cells

Cell Biol Int. 2018 Nov;42(11):1564-1574. doi: 10.1002/cbin.11052. Epub 2018 Sep 16.

Abstract

Ovarian cancer is one of the most common gyneacologic malignancies, with high morbidity and high mortality. Hsa-miR-122-5p (miR-122) has been reported with tumor-suppressing roles in various cancers. In this study, miR-122 was overexpressed in ovarian cancer cells, and phenotypic experiments demonstrated that miR-122 inhibited migration and invasion in SKOV3 and OVCAR3 cells. MiR-122 also suppressed epithelial mesenchymal transition (EMT), evidenced by expression changes of E-cadherin, vimentin, matrix metalloproteinase (MMP)2, and MMP14. Prolyl-4-hydroxylase subunit alpha-1 (P4HA1) was identified as a target of miR-122, and downregulated by miR-122. MiR-122-induced the elevation of migration, invasion, and EMT were recovered by P4HA1. Additionally, miR-122 restrained the tumor metastasis of SKOV3 cells in peritoneal cavity of nude mice. In summary, we demonstrated that miR-122 inhibited migration, invasion, EMT, and metastasis in peritoneal cavity of ovarian cancer cells by targeting P4HA1 for the first time, which shed lights on the discovery of miR-122 and P4HA1 as possible potential diagnostic markers and therapeutic targets for ovarian cancer.

Keywords: EMT; P4HA1; metastasis; miRNA.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary
  • Phenotype
  • Procollagen-Proline Dioxygenase / genetics*
  • Procollagen-Proline Dioxygenase / metabolism

Substances

  • MIRN122 microRNA, human
  • MicroRNAs
  • P4HA1 protein, human
  • Procollagen-Proline Dioxygenase