PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

Autor: Qinghua Li, Lu Chen, Dawei Chen, Shuanghai Liu, Jixue Zou, Zhenguo Zhao
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Cancer Research
Carcinoma
Hepatocellular
Immunology
Mice
Nude
Kaplan-Meier Estimate
Biology
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Prognostic markers
0302 clinical medicine
Cell Line
Tumor
Transcriptional regulation
Animals
Humans
Neoplasm Invasiveness
Phosphorylation
EP300
Promoter Regions
Genetic
Transcription factor
Cell Proliferation
Gene knockdown
Mice
Inbred BALB C
Serine-Arginine Splicing Factors
QH573-671
Cell growth
Alternative splicing
Cell Cycle
Liver Neoplasms
Cell Biology
Oncogenes
Cell cycle
Prognosis
Xenograft Model Antitumor Assays
digestive system diseases
Gene Expression Regulation
Neoplastic
Protein Phosphatase 2C
Alternative Splicing
030104 developmental biology
Mechanisms of disease
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Cancer research
Disease Progression
Cytology
Liver cancer
Protein Binding
Zdroj: Cell Death and Disease, Vol 12, Iss 8, Pp 1-11 (2021)
Cell Death & Disease
ISSN: 2041-4889
Popis: Emerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.
Databáze: OpenAIRE
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