Time serial transcriptome reveals Cyp2c29 as a key gene in hepatocellular carcinoma development

Qi Wang, Qin Tang, Lijun Zhao, et al.

Abstract


Objective: Hepatocellular carcinoma (HCC) is a severely lethal cancer that usually originates from chronic liver injury andinflammation. Although progress on diagnosis and treatment is obvious, the cause of HCC remains unclear. In this study, we soughtto determine key genes in HCC development.

Methods: To identify key regulators during HCC progression, we performed transcriptome sequencing to obtain time series geneexpression data from a mouse model with diethylnitrosamine-induced liver tumors and further verified gene expression andfunction in vitro and in vivo.

Results: Among the differentially expressed genes, Cyp2c29 was continuously downregulated during HCC progression.Overexpression of Cyp2c29 suppressed NF-κB activation and proinflammatory cytokine production by increasing the productionof 14,15-epoxyeicosatrienoic acid in vitro. Furthermore, overexpression of Cyp2c29 in vivo protected against liver inflammation inmouse models of liver injury induced by both acetaminophen and CCl4. Two human homologs of mouse Cyp2c29, CYP2C8 andCYP2C9, were found to be downregulated in human HCC progression, and their expression was positively correlated with overallsurvival in patients with HCC (significance: P = 0.046 and 0.0097, respectively).

Conclusions: Collectively, through systematic analysis and verification, we determined that Cyp2c29 is a novel gene involved in liverinjury and inflammation, which may be a potential biomarker for HCC prevention and prognosis determination.

Cite this article as: Wang Q, Tang Q, Zhao L, Zhang Q, Wu Y, Hu H, et al. Timeserial transcriptome reveals Cyp2c29 as a key gene in hepatocellular carcinomadevelopment. Cancer Biol Med. 2020; 17: 401-417. doi: 10.20892/j.issn.2095-3941.2019.0335


Keywords


Cyp2c29; hepatocellular carcinoma; NF-κB; proliferation; time series gene expression

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