黑色素瘤
癌症研究
生物
ATP柠檬酸裂解酶
细胞生长
脂肪酸合酶
体内
酶
生物化学
遗传学
柠檬酸合酶
作者
Yangzi Tian,Jingjing Ma,Meng‐Ru Wang,Xiuli Yi,Sen Guo,Hao Wang,Hengxiang Zhang,Huina Wang,Yuqi Yang,Baolu Zhang,Huiming Wang,Qiong Shi,Tianwen Gao,Chunying Li,Weinan Guo
摘要
Abstract The dysregulation of branched‐chain amino acid (BCAA) metabolism and related enzymes has been greatly implicated in the progression of multiple types of cancer, whereas remains far from understood in melanoma. Here, we explored the role of the BCAA metabolism enzyme BCKDHA in melanoma pathogenesis and elucidated the underlying mechanisms. In vitro cell biology experiments and in vivo pre‐clinical mice model experiments were performed to investigate the role of BCKDHA in melanoma progression. RNA sequencing, immunohistochemical/immunofluorescence staining and bioinformatics analysis were used to examine the underlying mechanism. BCKDHA expression was prominently increased in both melanoma tissues and cell lines. The up‐regulation of BCKDHA promoted long‐term tumour cell proliferation, invasion and migration in vitro and tumour growth in vivo. Through RNA‐sequencing technology, it was found that BCKDHA regulated the expressions of lipogenic fatty acid synthase (FASN) and ATP‐citrate lyase (ACLY), which was thereafter proved to mediate the oncogenic role of BCKDHA in melanoma. Our results demonstrate that BCKDHA promotes melanoma progression by regulating FASN and ACLY expressions. Targeting BCKDHA could be exploited as a promising strategy to restrain tumour progression in melanoma.
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