Weng Meilin, Zhang Hao, Hou Wenting, Sun Zhirong, Zhong Jing, Miao Changhong
Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
Onco Targets Ther. 2020 Apr 24;13:3477-3488. doi: 10.2147/OTT.S238973. eCollection 2020.
Colorectal cancer (CRC) is a major disease that threatens human health. It has been reported that the acyl-coenzyme A (CoA): cholesterol acyltransferase 2 () 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.
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.
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.
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.
结直肠癌（CRC）是一种威胁人类健康的主要疾病。据报道，酰基辅酶A（CoA）：胆固醇酰基转移酶2（）基因可促进肝细胞癌的进展，但其在结直肠癌中的作用仍不清楚。在本研究中，我们旨在阐明ACAT2在结直肠癌中的功能。
采用蛋白质免疫印迹法（Western blot）和定量聚合酶链反应（qPCR）检测结直肠癌组织及癌旁非癌组织中ACAT2的相对水平，然后评估ACAT2表达与结直肠癌患者临床病理特征及生存情况之间的关联。通过小干扰RNA（siRNA）下调CT26和DLD1细胞中ACAT2的表达，并检测ACAT2基因敲低对细胞增殖的影响。体内肿瘤生长实验进一步证实了ACAT2基因敲低的抑制作用。
我们的数据显示，结直肠癌组织中ACAT2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显著相关。ACAT2表达增加也与结直肠癌患者较差的5年总生存率显著相关。siRNA介导的ACAT2基因敲低强烈抑制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。敲低ACAT2表达可抑制体内结直肠癌的生长并抑制Ki67的表达。
我们的研究表明，ACAT2在调节结直肠癌增殖中发挥积极作用，可能作为该疾病潜在的生物标志物和治疗靶点。
