ACAT2 Promotes Cell Proliferation and Associates with Malignant Progression in Colorectal Cancer

• Main Authors: Weng M, Zhang H, Hou W, Sun Z, Zhong J, Miao C
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-04-01
• Series: OncoTargets and Therapy
• Subjects: acat2; cell proliferation; malignant progression; colorectal cancer.
• Online Access: https://www.dovepress.com/acat2-promotes-cell-proliferation-and-associates-with-malignant-progre-peer-reviewed-article-OTT

Meilin Weng,1,2,* Hao Zhang,1– 3,* Wenting Hou,1,2,* Zhirong Sun,1,2 Jing Zhong,1– 3 Changhong Miao1– 3 1Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changhong Miao; Jing ZhongDepartment of Anesthesiology, Floor 3, Building 3, No. 270 Dongan Road, Shanghai 200032 Tel [phone]Email [e-mail]; [e-mail] 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.Keywords: ACAT2, cell proliferation, malignant progression, colorectal cancer