Acetyl-CoA Carboxylase 1 (ACC1) Affects the Proliferation of Clear Cell Renal Cell Carcinoma (ccRCC) by Regulating Cyclin D1/CDK4
CHENG Jing1)##, NI Yue-Li1)##, AGBANA Yannick Luther1), YUN Fang1), YANG Hui1), ZHAO Lei3), LI Xiao-Yu1), ZHANG Xue-Dan1), ZHANG Qiao1), YANG Zhe2), KUANG Ying-Min3)*, ZHU Yue-Chun1)*
1)Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences,Kunming Medical University, Kunming 650500, China; 2)Department of Pathology,First Affiliated Hospital of Kunming Medical University, Kunming 650032, China; 3)Department of Organ Transplantation,First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
Abstract：Acetyl-CoA carboxylase (ACC) is the rate limiting enzyme of fatty acid synthesis pathway. Studies have shown that ACC1 is implicated in a variety of metabolic diseases and cancer. However, the role and mechanism of action of ACC1 in clear cell renal cell carcinoma (ccRCC) have not been reported. In this study, 786-O and Caki-1 clear cell renal carcinoma cells were used as research objects to investigate the effect of abnormal expression of ACC1 on their proliferation and unravel the underlying mechanism. Red oil-O-staining results showed that the lipid content of 786-O and Caki-1 cells was significantly higher than that of human kidney 2 (HK2) cells. By searching TCGA database, we found that the expression of ACC1 proteins in ccRCC was significantly higher than that in normal renal tissues (P < 0.001). Plus, ACC1 protein expression in all clinical TNM stages was significantly higher than that in normal tissues, and the higher the expression of ACC1, the higher the pathological grade. Furthermore, high expression of ACC1 mRNA is positively correlated with poor prognosis in ccRCC patients. Western blotting analysis showed that the expression of ACC1 in 786-O and Caki-1 cells was significantly higher than that in HK2 cells. The results of red oil-O-staining showed that knocking down ACC1 could significantly reduce the lipid content of 786-O and Caki-1 cells. The results of CCK-8 assays and clonogenicity analysis showed that knocking down ACC1 could significantly reduce the proliferation and colony forming ability of 786-O and Caki-1 cells. Flow cytometry analysis showed that after knocking down ACC1, the cell cycle was blocked at the G0/G1 phase and the expression of Cyclin D1 and CDK4 was inhibited. In conclusion, we found that ACC1 is abnormally overexpressed in ccRCC and it favors proliferation by regulating the expression of Cyclin D1 and CDK4. Therefore, ACC1 is a potential target for the treatment of ccRCC.
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