A micropeptide JunBP regulated by TGF-β promotes hepatocellular carcinoma metastasis.
Hongwei ZhangZhibin LiaoWeijian WangYachong LiuHe ZhuHui-Fang LiangBixiang ZhangXiao-Ping ChenPublished in: Oncogene (2022)
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.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- signaling pathway
- long non coding rna
- amino acid
- cell proliferation
- long noncoding rna
- pi k akt
- gene expression
- binding protein
- dna methylation
- transcription factor
- risk assessment
- induced apoptosis
- oxidative stress
- small molecule
- human health
- climate change