Clinical significance of microRNA-125b and its contribution to ovarian carcinogenesis

Bioengineered. 2020 Dec;11(1):939-948. doi: 10.1080/21655979.2020.1814660.

Abstract

The underlying mechanisms of recurrence and metastasis of epithelial ovarian cancer (EOC) are largely unknown. In the present study, we investigated the clinical significance of microRNA-125b (miR-125b) and its role in ovarian tumorigenesis and progression. Seventy patients of EOC and paired tissues were enrolled from 2015 to 2017. qRT-PCR was used to evaluate miR-125b expression in tumor tissues and EOC cell line. Gain-and-loss function of miR-125b was achieved to explore the changes in cell biological function. We found that miR-125b expression in EOC tissues, especially in the high-grade tissues (P < 0.001), was significantly lower compared to the matched adjacent noncancerous tissues and associated with pathological type, stage, and overall survival (P < 0.05). Upregulation of miR-125b promoted apoptosis and decreased cell survival rate and migration, and vice versa in vitro. Mechanistically, miR-125b negatively regulated S100A4, a metastasis-associated protein. MiR-125b overexpression significantly decreased tumor growth and inhibited lung metastasis in vivo. Our results supported that miR-125b contributes to the progression of EOC by targeting S100A4. It potentially acts as a potential biomarker and therapeutic target of EOC.

Keywords: Ovarian cancer; S100a4; metastasis; miR-125b.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / pathology*
  • Female
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium-Binding Protein A4 / genetics
  • S100 Calcium-Binding Protein A4 / metabolism
  • Young Adult

Substances

  • MIRN125 microRNA, human
  • MicroRNAs
  • S100 Calcium-Binding Protein A4
  • S100A4 protein, human