Downregulation of acetyl-CoA synthase 2 inhibits non-small cell lung cancer cell proliferation by inducing autophagy
FAN Xueyu1, ZHANG Feng2, WENG Yuanyuan1, WANG Siwei2, YANG Liping1, ZHU Jin1
1.Department of Clinical Laboratory, the Quzhou Affiliated Hospital of Wenzhou Medical University (Quzhou People’s Hospital), Quzhou 324000, China; 2.Core Facility, the Quzhou Affiliated Hospital of Wenzhou Medical University (Quzhou People’s Hospital), Quzhou 324000, China
FAN Xueyu,ZHANG Feng,WENG Yuanyuan, et al. Downregulation of acetyl-CoA synthase 2 inhibits non-small cell lung cancer cell proliferation by inducing autophagy[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(11): 868-815.
Abstract：Objective: To investigate the expression of acetyl-CoA synthase 2 (ACSS2) in non-small cell lung cancer (NSCLC) cells and its regulatory mechanism of cell proliferation and invasion. Methods: Western blot was used to detect and analyze the difference of ACSS2 expression in NSCLC cell lines A549 and H1299 and human fibroblast cell HFF-1; ACSS2 knockdown (ACSS2 KD group) and control cell lines (NC group) were constructed in NSCLC cell lines using lentivirus. The effect of ACSS2 on the proliferation of NSCLC cells was analyzed by MTT assay and cell clone formation assay. The effect of ACSS2 on the migration and invasion ability of NSCLC cells were analyzed by scratch assay and transwell assay. The effect of ACSS2 knockdown on autophagy was analyzed. Western blot and immunofluorescence experiments. Results: The protein level of ACSS2 in NSCLC cells was significantly increased compared with human fibroblast HFF-1 (P<0.05). Knockdown of ACSS2 significantly reduced cell proliferation and cell viability. ACSS2 KD group also significantly reduced the migratory and invasive abilities of NSCLC cells (both P<0.01). Western blot and immunofluorescence experiments showed that knockdown of ACSS2 significantly increased the autophagy activity and the number of autophagosomes (P<0.01). However, knockdown of ACSS2 hardly affected the protein expression of caspase3 and caspase8 (P>0.05). A549 cells were co-transfected with ACSS2-shRNA+Beclin1/Atg7-shRNA and the results showed that the cell proliferation ability of the ACSS2-shRNA+Beclin1/Atg7-shRNA group was enhanced and the number of clones increased significantly compared with the ACSS2 KD group. Conclusion: ACSS2 is highly expressed in NSCLC cells, which promotes cell proliferation and invasion. Down-regulation of ACSS2 can induce autophagic cell death in NSCLC cells and inhibit cell proliferation.
