ACAT2 Promotes Cell Proliferation and Associates with Malignant Progression in Colorectal Cancer
ACAT2 Promotes Cell Proliferation and Associates with Malignant Progression in Colorectal Cancer
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DOI：
10.2147/ott.s238973
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发表时间：
2020-04
影响因子：
4
通讯作者：
M. Weng;Hao Zhang;Wenting Hou;Zhirong Sun;Jing Zhong;C. Miao
中科院分区：
文献类型：
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作者：
M. Weng;Hao Zhang;Wenting Hou;Zhirong Sun;Jing Zhong;C. Miao
背景与目的结直肠癌（Colorectal cancer， CRC）是威胁人类健康的主要疾病。有报道称酰基辅酶A (CoA)：胆固醇酰基转移酶2 （ACAT2）基因可促进肝细胞癌的进展，但其在结直肠癌中的功能尚不清楚。在本研究中，我们旨在阐明ACAT2在CRC中的功能。方法采用Western blot和qPCR检测结直肠癌组织及癌旁非癌组织中ACAT2的相对表达水平，评估ACAT2表达与结直肠癌患者临床病理特征及生存的关系。通过siRNA下调CT26和DLD1细胞中ACAT2的表达，检测ACAT2下调对细胞增殖的影响。体内肿瘤生长实验进一步证实了ACAT2敲低的抑制作用。结果ACAT2在结直肠癌组织中的表达明显高于癌旁非癌组织。ACAT2的高表达与肿瘤大小、淋巴结转移及临床分期有显著相关性。ACAT2表达升高也与CRC患者5年总生存率降低显著相关。sirna介导的ACAT2敲低强烈抑制CT26和DLD1细胞的增殖，并诱导这些细胞的G0/G1期细胞周期阻滞和凋亡。在体内，ACAT2表达下调可抑制CRC的生长，抑制Ki67的表达。结论本研究表明ACAT2在调节结直肠癌的增殖中发挥积极作用，可能作为结直肠癌的潜在生物标志物和治疗靶点。
Background and Aims Colorectal cancer (CRC) is a major disease that threatens human health. It has been reported that the acyl-coenzyme A (CoA): cholesterol acyltransferase 2 (ACAT2) gene can promote the progression of hepatocellular carcinoma, but its function in CRC is still unclear. In this study, we aimed to elucidate the function of ACAT2 in CRC. Methods Western blot and qPCR were used to detect the relative level of ACAT2 in CRC tissue and adjacent non-cancerous tissues, and then the association between ACAT2 expression and the clinicopathological features and survival of CRC patients were assessed. The expression of ACAT2 in CT26 and DLD1 cells was down-regulated by siRNA, and the effects of ACAT2 knockdown on cell proliferation were examined. The inhibitory effects of ACAT2 knockdown were further confirmed by tumor growth assays in vivo. Results Our data showed that the expression of ACAT2 in CRC tissues was markedly higher than in adjacent non-cancerous tissues. The high expression of ACAT2 was significantly associated with tumor size, lymph node metastasis and clinical stage. The increased expression of ACAT2 was also significantly associated with worse 5-year overall survival of CRC patients. siRNA-mediated ACAT2 knockdown strongly inhibited CT26 and DLD1 cells proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in these cells. Knockdown of ACAT2 expression suppressed the growth of CRC and inhibited the expression of Ki67 in vivo. Conclusion Our study demonstrated that ACAT2 played a positive role in regulating the proliferation of CRC and may be useful as a potential biomarker and therapeutic target for this disease.