ACC2 is under-expressed in lung adenocarcinoma and predicts poor clinical outcomes
ACC2 is under-expressed in lung adenocarcinoma and predicts poor clinical outcomes
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ACC2 在肺腺癌中表达不足，预示临床结果不佳
DOI：
10.1007/s00432-021-03910-1
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发表时间：
2022-01-22
影响因子：
3.6
通讯作者：
Xu，Yan-Ming
中科院分区：
文献类型：
--
作者：
Yu，Fei-Yuan;Xu，Qian;Xu，Yan-Ming
目的乙酰辅酶a羧化酶（ACCs）是催化乙酰辅酶a羧化为丙二酰辅酶a的关键脂肪酸代谢酶。ACC1的作用与肿瘤生物学有关，但ACC2在癌症中的作用在很大程度上仍未确定。方法利用GEPIA和Oncomine进行转录组学分析，研究ACC2在不同肿瘤中的表达。采用免疫组化方法检测肺癌组织芯片中ACC2的表达，并分析ACC2表达与临床参数的相关性。在A549和HCC827细胞中通过RNA干扰敲低ACC2后，使用Cell Counting Kit - 8和transwell检测细胞增殖和迁移。采用Real-time PCR检测A549细胞中细胞周期相关基因。采用GEO数据集和KM-plotter数据库分析肺癌患者ACC2表达与预后的关系。结果ACC2在癌组织中低表达，其表达与肺腺癌患者肿瘤大小、局部淋巴结转移及临床分期呈负相关。此外，在A549细胞和HCC827细胞中敲低ACC2可促进细胞增殖和迁移，并且在A549细胞中敲低ACC2后，细胞周期相关基因MAD2L1和CCNB2上调。最后，我们发现低表达ACC2的肺腺癌患者预后较差。结论ACC2是肺腺癌的潜在诊断和预后指标，与临床预后呈负相关。
PurposeAcetyl-CoA Carboxylases (ACCs) are key fatty acid metabolic enzymes responsible for catalyzing the carboxylation of acetyl-CoA to malonyl-CoA. The role of ACC1 has been associated with tumor biology, but the role of ACC2 in cancer remains largely uncharacterized.MethodsWe conducted a transcriptomic analysis using GEPIA and Oncomine to study the expression of ACC2 in different cancers. Immunohistochemistry was used to examine the expression of ACC2 in lung cancer tissue microarray, and the correlation between ACC2 expression and clinical parameters was analyzed. Following ACC2 knockdown by RNA interference in A549 and HCC827 cells, Cell Counting Kit‑8 and transwell assays were used to detect cell proliferation and migration. Real-time PCR was used to detect cell cycle-related genes in A549 cells. GEO dataset and KM-plotter database were used to analyze the relationship between ACC2 expression and the prognosis in lung cancer patients.ResultsWe found that ACC2 is under-expressed in cancerous tissue and the expression of ACC2 is negatively correlated with tumor size, regional lymph-node metastases, and clinical stage of lung adenocarcinoma patients. In addition, knocking down ACC2 in A549 cells and HCC827 cells can promote cell proliferation and migration, and cell cycle-related genes MAD2L1 and CCNB2 were up-regulated after ACC2 was knockdown in A549 cells. Finally, we found that lung adenocarcinoma patients with under-expressed ACC2 have a worse prognosis.ConclusionsOur results suggest that ACC2 is a potential diagnostic and prognostic marker that negatively correlated with clinical outcomes in lung adenocarcinoma.