Sohlh2 alleviates malignancy of EOC cells under hypoxia via inhibiting the HIF1α/CA9 signaling pathway

Biol Chem. 2020 Feb 25;401(2):263-271. doi: 10.1515/hsz-2019-0119.

Abstract

Epithelial ovarian cancer (EOC) is the most common and deadly ovarian cancer. Most of the patients have abdominal/pelvic invasion and metastasis at the time of diagnosis, but the underlying mechanism remains unclear. Insufficiency of blood perfusion and diffusion within most solid tumors can lead to a hypoxic tumor microenvironment and promotes tumor malignancy. In the present study, we detected the role of the spermatogenesis- and oogenesis-specific basic helix-loop-helix (bHLH) transcription factor 2 (sohlh2) on migration, invasion and epithelial-mesenchymal transition (EMT) of EOC cell lines under hypoxia in vitro. We also investigated the possible mechanism underlying it. The results showed that sohlh2 inhibited the migration, invasion and EMT of EOC cells and might function through suppression of the hypoxia-inducible factor 1α (HIF1α)/carbonic anhydrase 9 (CA9) signaling pathway. Our results may open a new avenue for the further development of diagnostic tools and novel therapeutics that will benefit EOC patients.

Keywords: EMT; EOC; HIF1α/CA9 pathway; hypoxia; sohlh2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Carbonic Anhydrase IX / metabolism*
  • Carcinoma, Ovarian Epithelial / metabolism*
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Hypoxia*
  • Cell Line
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Signal Transduction*

Substances

  • Antigens, Neoplasm
  • Basic Helix-Loop-Helix Transcription Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • SOHLH2 protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX