A micropeptide JunBP regulated by TGF-β promotes hepatocellular carcinoma metastasis

Oncogene. 2023 Jan;42(2):113-123. doi: 10.1038/s41388-022-02518-0. Epub 2022 Nov 15.

Abstract

Transforming growth factor beta (TGF-β) signaling pathway plays important roles in hepatocellular carcinoma (HCC) progression. Long intergenic non-protein coding RNAs (lincRNAs) are important components of TGF-β signaling pathway and perform their functions through different mechanisms. Here, we found that LINC02551 was activated by TGF-β transcriptionally and identified a 174-amino-acid peptide, Jun binding micropeptide (JunBP), encoded by LINC02551 in HCC tissues and HCC cell lines. Functional study showed that JunBP promotes HCC metastasis through binding to c-Jun and subsequent promotion of its phosphorylated activation. Activated c-Jun has higher binding affinity to SMAD3, which in turn leads to more SMAD3 recruited to the promoter region of LINC02551. We find a positive feedback among them, and this mechanism provides a novel potential prognostic biomarker and therapeutic target in HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Humans
  • Liver Neoplasms* / pathology
  • Micropeptides
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta