Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China.
Clin Transl Oncol. 2023 Aug;25(8):2499-2513. doi: 10.1007/s12094-023-03137-1. Epub 2023 Mar 28.
The de novo lipogenesis has been a longstanding observation in hepatocellular carcinoma (HCC). However, the prognostic value and carcinogenic roles of the enzyme Acetyl-CoA carboxylase alpha (ACACA) in HCC remains unknown.
The proteins with remarkable prognostic significance were screened out from The Cancer Proteome Atlas Portal (TCPA) database. Furthermore, the expression characteristics and prognostic value of ACACA were evaluated in multiple databases and the local HCC cohort. The loss-of-function assays were performed to uncover the potential roles of ACACA in steering malignant behaviors of HCC cells. The underlying mechanisms were conjectured by bioinformatics and validated in HCC cell lines.
ACACA was identified as a crucial factor of HCC prognosis. Bioinformatics analyses showed that HCC patients with higher expression of ACACA protein or mRNA levels had poor prognosis. Knockdown of ACACA remarkably crippled the proliferation, colony formation, migration, invasion, epithelial-mesenchymal transition (EMT) process of HCC cells and induced the cell cycle arrest. Mechanistically, ACACA might facilitate the malignant phenotypes of HCC through aberrant activation of Wnt/β-catenin signaling pathway. In addition, ACACA expression was associated with the dilute infiltration of immune cells including plasmacytoid DC (pDC) and cytotoxic cells by utilization of relevant database analysis.
ACACA could be a potential biomarker and molecular target for HCC.
从头合成脂肪生成在肝细胞癌（HCC）中是一个长期存在的观察结果。然而，酶乙酰辅酶 A 羧化酶 α（ACACA）在 HCC 中的预后价值和致癌作用尚不清楚。
从癌症蛋白质组图谱门户（TCPA）数据库中筛选出具有显著预后意义的蛋白质。此外，在多个数据库和本地 HCC 队列中评估了 ACACA 的表达特征和预后价值。进行功能丧失测定以揭示 ACACA 在指导 HCC 细胞恶性行为中的潜在作用。通过生物信息学推测潜在机制，并在 HCC 细胞系中进行验证。
ACACA 被确定为 HCC 预后的关键因素。生物信息学分析表明，ACACA 蛋白或 mRNA 水平较高的 HCC 患者预后较差。ACACA 的敲低显著削弱了 HCC 细胞的增殖、集落形成、迁移、侵袭和上皮-间充质转化（EMT）过程，并诱导细胞周期停滞。在机制上，ACACA 可能通过异常激活 Wnt/β-连环蛋白信号通路促进 HCC 的恶性表型。此外，通过利用相关数据库分析，ACACA 表达与免疫细胞（包括浆细胞样树突状细胞（pDC）和细胞毒性细胞）的稀疏浸润有关。
ACACA 可能是 HCC 的潜在生物标志物和分子靶标。
