关键词: 前列腺癌, 乙酰辅酶A羧化酶α, 固醇调节元件结合蛋白1(SREBP1), Warburg效应, 脂质代谢

Abstract: Objective Exploring the expression of sterol regulatory element-binding protein 1 (SREBP1) and acetyl-CoA carboxylase alpha(ACCα) in prostate cancer tissues and their impact on proliferation, migration and invasion of prostate cancer cells DU145. Methods The expression levels of SREBP1 and ACCα in prostate cancer tissue were analyzed using online databases including TIMER, UALCAN, GEPIA, and THE HUMAN PROTEIN ATLAS. Paraffin-embedded specimens from 58 cases of prostate cancer (PCa) and 58 cases of benign prostatic hyper- plasia(BPH) diagnosed at the Fifth Affiliated Hospital of Zunyi Medical University from January 2016 to December 2018 were collected. Immunohistochemistry was used to detect the expression of SREBP1 and ACCα in these tissues. Following the knockdown of SREBP1 in DU145 cells using shRNA, the changes in ACCα expression were assessed by qRT-PCR. The CCK-8 assay was employed to evaluate cell proliferation, while flow cytometry was used to analyze cell cycle distribution. Western blot was performed to measure the expression of SREBP1 and ACCα. Transwell assays were conducted to assess changes in migration and invasion capabilities after silencing SREBP1 in DU145 cells. Scratch assays were used to examine the impact of SREBP1 knockdown on the healing capability of DU145 cells. EdU assays were performed to detect changes in cell proliferation following the silencing of SREBP1. Oil Red O staining was utilized to observe changes in lipid content within prostate cancer cells after interference with SREBP1 expression. Results Analysis using online databases such as TIMER and UALCAN revealed that ACCα expression was significantly elevated in prostate cancer tissues compared to normal prostate tissues (P＜0.001). After silencing SREBP1, the proliferation, migration and invasion capability of DU145 cells were significantly reduced compared to the control group (P＜0.01), and flow cytometric analysis showed G1 phase arrested in DU145 cells (P＜0.01). Knockdown of SREBP1 resulted in a significant decrease in lipid content in prostate cancer cells (P＜0.01). Conclusions SREBP1 may promote the proliferation, migration and invasion of prostate cancer cells through regulating the expression of ACCα.

Key words: prostate cancer, acetyl-CoA carboxylase alpha, sterol regulatory element-binding protein 1(SREBP1), Warburg effect, lipid metabolism