Loss of STAT5A promotes glucose metabolism and tumor growth through miRNA-23a-AKT signaling in hepatocellular carcinoma

Mol Oncol. 2021 Feb;15(2):710-724. doi: 10.1002/1878-0261.12846. Epub 2020 Nov 22.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Here, we identified that increased miR-23a expression in HCC tissues was associated with worse survival. More importantly, we found that STAT5A was a target of miR-23a, whose levels significantly decreased in tumor tissues. Stable expression of STAT5A in Huh7 cells suppressed glucose metabolism and tumor growth. Finally, this study showed that increased miR-23a negatively regulated STAT5A, which further activated AKT signaling to enable rapid metabolism for accelerated tumor growth in HCC. Taken together, our results demonstrated that the miR-23a-STAT5A-AKT signaling pathway is critical to alter glucose metabolism in HCC and may offer new opportunities for effective therapy.

Keywords: AKT; STAT5A; glucose metabolism; hepatocellular carcinoma; miR-23a; tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Glucose / genetics
  • Glucose / metabolism*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • MIRN23a microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-akt
  • Glucose