LYPLAL1通过调控前列腺癌细胞线粒体自噬促进增殖、迁移和侵袭的机制研究OA

Objective To investigate the mechanism of lysophospholipase-like 1(LYPLAL1)in promoting the proliferation,mi-gration and invasion of prostate cancer cells by regulating mitophagy.Methods Cancer foci and adjacent normal tissue samples of 30 prostate cancer patients admitted to the First Hospital of Zhangjiakou City from June 2023 to March 2024 were collected.The mRNA and/or protein expression levels of LYPLAL1 in prostate and paracancer tissues,prostate epithelial cellsand prostate cancer cells were detected by quantitative real time polymerase chain reaction(qRT-PCR)and Western blot.DU145 cells were divided into control group(without any treatment),si-NC group(transfected with control si-NC sequence),si-LYPLAL1 group(transfected with interference si-LYPLAL1 sequence),CQ group(pretreated with autophagy blocker CQ 10μmol/L)and si-LY-PLAL1+CQ group(transfected with si-LYPLAL1 sequence and treated with CQ).The effects of LYPLAL1 expression on the proliferation,migration and invasion of DU145 cells were detected by CCK-8 assay,scratch assay and Transwell assay.The ex-pression level of mitochondria autophagy related proteins[Microtubuleassociated protein light chain 3(LC3-Ⅱ),p62,PTEN in-duced putative kinase 1(PINK1),parkin]was detected by Western blot.Results The expression levels of LYPLAL1 mRNA(2.65±0.21 vs 1.03±0.04)and protein(2.74±0.25 vs 1.02±0.03)in prostate cancer tissues were significantly higher than those in adjacent normal tissues,the differences were statistically significant(t=41.507,37.415,all P<0.001).Compared with prostate epithelial cell BPH-1,the expression levels of LYPLAL1 mRNA in prostate cancer cells LNCaP,PC-3 and DU145 were signifi-cantly increased,the differences were statistically significant(t=5.826,6.483,7.509,all P<0.001).Compared with the control group,the cell proliferation rate(53.56%±2.67%vs 98.42%±5.63%),migration rate(48.61%±2.53%vs 100.40%±6.03%)and invasion rate(98.75%±5.35%vs 99.16%±5.58%)in the si-LYPLAL1 group were significantly decreased,the differences were statistically significant(t=11.459,12.531,12.754,all P<0.05).Compared with the control group,the protein expressions of LC3-II(2.35±0.20 vs 0.99±0.04),parkin(2.68±0.18 vs 1.00±0.02)and PINK1(2.56±0.17 vs 0.98±0.03)in the si-LYPLAL1 group were significantly increased,and the protein expression of p62(0.55±0.05 vs 1.01±0.03)was significantly inhibited,the differences were statistically significant(t=13.994～19.413,all P<0.05).The CQ group inhibited the effect of LYPLAL1 disrup-tion on the biology of prostate cancer cells.Conclusions The up-regulation of LYPLAL1 expression in prostate cancer may me-diate the proliferation,migration and invasion of prostate cancer cells through the regulation of mitochondrial autophagy path-way,and participate in the malignant progression of prostate cancer.