Integrated analysis of transcriptomics and metabolomics in human hepatocellular carcinoma HepG2215 cells after YAP1
Yuting Gao1, Yi Gong2, Yiwei Liu2
1Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
Abstract:
Yes-associated protein 1 (YAP1) plays a critical role in hepatocellular carcinoma (HCC). Inhibition of YAP1 expression suppresses HCC progression, but the underlying mechanism is still unclear. In this study, we studied the effects and molecular mechanisms of YAP1 knockdown on the growth and metabolism in human HCC HepG2215 cells. Inhibition of YAP1 expression inhibits the proliferation and metastasis in HepG2215 cells, and differentially expressed genes (DEGs) and metabolites were identified in shYAP1-HepG2215 cells. Further, 805 DEGs, mainly associated with metabolism and particularly lipid metabolism, were identified by transcriptome sequencing analyses in shYAP1-HepG2215 cells. YAP1 knockdown increased albumin (ALB) levels by Protein-protein interaction (PPI) network analyses in HepG2215 cells. Metabolomic profiling identified 37 metabolites with significant differences in the shYAP1 group, and amino acid metabolism generally decreased in the shYAP1 group. Comprehensive analysis of transcriptomics and metabolomics revealed that the ATP-binding cassette (ABC) transporters play a central role after YAP1 knockdown in HepG2215 cells. Therefore, YAP1 knockdown inhibited HCC growth, which affected the metabolism of lipids and amino acids by regulating the expression of ALB and ABC transporters in HepG2215 cells.
Insights
Inhibiting Yes-associated protein 1 (YAP1) in liver cancer cells (HCC) reduced tumor growth and altered lipid and amino acid metabolism. YAP1 knockdown affected albumin (ALB) and ATP-binding cassette (ABC) transporters, revealing new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Metabolomics
Background:
- Yes-associated protein 1 (YAP1) is crucial in hepatocellular carcinoma (HCC) progression.
- Inhibiting YAP1 suppresses HCC growth, but mechanisms require elucidation.
Purpose of the Study:
- To investigate the effects and molecular mechanisms of YAP1 knockdown on HCC cell growth and metabolism.
- To identify key genes and metabolites affected by YAP1 inhibition in HepG2215 cells.
Main Methods:
- Transcriptome sequencing to identify differentially expressed genes (DEGs) in YAP1-knockdown HepG2215 cells.
- Metabolomic profiling to analyze metabolic changes.
- Protein-protein interaction (PPI) network analysis to explore molecular interactions.
Main Results:
- YAP1 knockdown inhibited proliferation and metastasis in HepG2215 cells.
- Transcriptomics revealed 805 DEGs, primarily linked to lipid metabolism.
- Metabolomics identified 37 differential metabolites, with decreased amino acid metabolism.
- YAP1 knockdown increased albumin (ALB) levels and highlighted the role of ATP-binding cassette (ABC) transporters.
Conclusions:
- YAP1 knockdown inhibits HCC growth by modulating lipid and amino acid metabolism.
- Regulation of ALB and ABC transporters are key mechanisms underlying YAP1 inhibition effects in HCC.
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