MicroRNA-1 inhibits ovarian cancer cell proliferation and migration through c-Met pathway

Clin Chim Acta. 2017 Oct:473:237-244. doi: 10.1016/j.cca.2017.07.008. Epub 2017 Jul 8.

Abstract

In this study, we investigated the differential expression of microRNAs in an ovarian cancer cell line HO-8910PM with increased migration and invasiveness activities. miR-1 was found to be one of the microRNA species most significantly downregulated in HO-8910PM compared with the control cell line HO-8910. We demonstrated that ovarian cancer tissues expressed decreased levels of miR-1 compared to non-neoplastic tissues. In vitro experiments showed that overexpression of miR-1 in HO-8910PM led to an inhibition of cell proliferation, blocking of cell cycle progression by G1 phase arrest, and decreased migration and invasiveness of HO-8910PM cells. Moreover, we confirmed that the expression of c-Met, a potential target of miR-1, was significantly inhibited following overexpression of miR-1 in HO-8910PM cells. Further analyses indicated that expression of factors including p-Akt, p-ERK1/2, CDK4, and p-Rb in HO-8910PM cells were affected by manipulation of c-Met expression. Infection of HO-8910PM cells with lentivirus vector expressing miR-1 led to a significant inhibition of tumor growth in the tumor subcutaneous nude mouse model. Taken together, these results indicated that miR-1 is downregulated in ovarian cancer tissues, and may play a tumor suppressive role by inhibiting c-Met expression and its effects on the regulation of cell proliferation, migration and invasion.

Keywords: Migration; Ovarian cancer; Proliferation; c-Met; miR-1.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Female
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Proto-Oncogene Proteins c-met / genetics*
  • Signal Transduction / genetics*

Substances

  • MIRN1 microRNA, human
  • MicroRNAs
  • MET protein, human
  • Proto-Oncogene Proteins c-met