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Updated: Aug 21, 2025

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Published on: October 27, 2020
A micropeptide JunBP regulated by TGF-β promotes hepatocellular carcinoma metastasis
Hongwei Zhang1,2, Zhibin Liao1,2, Weijian Wang1,2
1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
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.
Insights
Transforming growth factor beta (TGF-β) activates LINC02551, which produces JunBP. This peptide promotes hepatocellular carcinoma (HCC) metastasis via a positive feedback loop, offering new therapeutic targets for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Transforming growth factor beta (TGF-β) signaling is crucial in hepatocellular carcinoma (HCC) progression.
- Long intergenic non-protein coding RNAs (lincRNAs) are integral to TGF-β signaling pathways.
Purpose of the Study:
- To investigate the role of LINC02551 and its encoded peptide in HCC.
- To elucidate the mechanism by which LINC02551 influences HCC metastasis.
Main Methods:
- Transcriptional analysis of LINC02551 activation by TGF-β.
- Identification and characterization of the Jun binding micropeptide (JunBP).
- Functional studies on JunBP's interaction with c-Jun and SMAD3 in HCC cell lines.
Main Results:
- LINC02551 is transcriptionally activated by TGF-β.
- A novel peptide, JunBP, encoded by LINC02551, was identified in HCC.
- JunBP promotes HCC metastasis by activating c-Jun, which enhances SMAD3 binding to the LINC02551 promoter, creating a positive feedback loop.
Conclusions:
- A novel molecular mechanism involving LINC02551, JunBP, c-Jun, and SMAD3 drives HCC progression.
- This pathway represents a potential prognostic biomarker and therapeutic target for HCC.
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