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.

Oncogene
|November 15, 2022
PubMed

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.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.9K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.7K