microRNA-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis of esophageal squamous cell carcinoma

J Biochem Mol Toxicol. 2022 Nov;36(11):e23182. doi: 10.1002/jbt.23182. Epub 2022 Aug 8.

Abstract

Aberrant expression of microRNA-497 (miR-497) is associated with tumor progression, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we report that miR-497 expression is downregulated in esophageal squamous cell carcinoma (ESCC) clinical samples. Consistently, upregulation of miR-497 inhibits ESCC cell malignant properties and tumor growth in vivo. Importantly, we uncovered that miR-497 upregulation suppressed ESCC cell growth and tumor growth by inhibiting Smurf2. Mechanistically, we showed that Smurf2 was a target of miR-497, and mediated YY1 expression to elevate HIF2α expression, thereby enhancing the malignancy of ESCC cells. Together, our study uncovered the role of the miR-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis, which might provide potential therapeutic targets for human ESCC.

Keywords: HIF2α; MicroRNA-497; Smurf2; YY1; esophageal squamous cell carcinoma; tumor metastasis.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Neoplasm Invasiveness / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Up-Regulation
  • YY1 Transcription Factor / genetics
  • YY1 Transcription Factor / metabolism

Substances

  • MicroRNAs
  • SMURF2 protein, human
  • Ubiquitin-Protein Ligases
  • YY1 protein, human
  • YY1 Transcription Factor
  • MIRN497 microRNA, human