<scp>BCAT</scp>1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin

Abstract

Abstract Background &amp; Aims BCAT 1 initiates the catabolism of branched‐chain amino acids. Here, we investigated the function of BCAT 1 and its transcriptional regulatory mechanism in hepatocellular carcinoma ( HCC ). Methods RNASeq was used to evaluate BCAT 1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT 1 in BEL ‐7404 cells and the suppression of endogenous BCAT 1 expression with sh RNA in HepG2 cells, the cell proliferation, clone‐forming ability and cell‐cycle changes were measured with MTT assay, colony‐forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT 1 on cancer growth in vivo . Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT 1 gene by MYC . The expression of the BCAT 1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. Results BCAT 1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT 1 in BEL ‐7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S–G 2 /M phase transition and chemoresistance to cisplatin. The suppression of BCAT 1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S–G 2 /M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT 1. Clinical data showed that BCAT 1 expression correlated with a significantly poorer prognosis. Conclusion BCAT 1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT 1. BCAT 1 expression has prognostic significance for the survival of patients with HCC .