FAIM modulates HCC progression via enhancing HMGA1 interaction with CDK7 and promoting its phosphorylation level
Yuan Li1, Wenna Liu2, Xushen Fan2
1Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450003, Henan, China.
Fas apoptotic inhibitory molecule (FAIM) promotes hepatocellular carcinoma (HCC) by increasing High mobility group A1 (HMGA1) phosphorylation and stability, involving cyclin-dependent kinase7 (CDK7). This research clarifies FAIM
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) is a deadly cancer with rapid progression.
- Fas apoptotic inhibitory molecule (FAIM) inhibits apoptosis and is implicated in cancer.
- High mobility group A1 (HMGA1) is crucial in HCC development, but its regulation by FAIM is unknown.
Purpose of the Study:
- To investigate the role of FAIM in HCC progression.
- To determine if FAIM modulates HMGA1 phosphorylation.
- To elucidate the mechanism by which FAIM influences HCC.
Main Methods:
- Utilized HCC cell lines (Huh7, SNU387) and a mouse model.
- Performed proteomic and phosphorylation proteomic analyses.
- Conducted immunoprecipitation and in vitro kinase assays.
Main Results:
- FAIM overexpression accelerated HCC progression in vitro and in vivo.
- FAIM was found to interact with CDK7 and HMGA1.
- FAIM enhanced HMGA1 phosphorylation at Ser36, increasing its stability.
Conclusions:
- FAIM promotes HCC by enhancing HMGA1 phosphorylation and stability.
- FAIM facilitates the interaction between CDK7 and HMGA1.
- This study reveals a novel mechanism of HCC pathogenesis involving FAIM and HMGA1.
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