山西医科大学学报2025,Vol.56Issue(5):516-523,8.DOI:10.13753/j.issn.1007-6611.2025.05.008
下调Pin1通过Akt/SREBP-1轴抑制宫颈癌细胞增殖
Pin1 knockdown inhibits cervical cancer cell proliferation via the Akt/SREBP-1 axis
摘要
Abstract
Objective To investigate the effect of peptidylprolyl cis/trans isomerase,NIMA-interacting 1(Pin1)knockdown on the proliferation and apoptosis of cervical cancer cells and its mechanism.Methods The mRNA expressions of Pin1 and sterol regula-tory element-binding protein 1(SREBP1)in normal cervical tissues and cervical cancer tissues were detected,and the relationship be-tween them was analyzed based on the online TNMplot platform and R2:Genomics Analysis and Visualization Platform.The expres-sions of Pin1 and SREBP-1 proteins in clinical specimens of cervical cancer tissues and cervicitis tissues were detected by immunohis-tochemistry,and their correlation was analyzed.Pin1 expression was detected in cervical cancer cells and normal cervical epithelial cells by Western blot.The experiment was divided into three groups:sh-NC group,shPin1-A group,and shPin1-B group.Human cer-vical squamous carcinoma SiHa cells were transfected with lentivirus to establish a stable cell line with low Pin1 expression.The ex-pression of Pin1 was evaluated by Western blot to verify the transfection efficiency.The proliferation and the apoptosis of SiHa cells were detected after Pin1 knockdown by CCK-8 assay and flow cytometry.The expressions of protein kinase B(Akt),phosphorylated protein kinase B(p-Akt),SREBP1,and apoptosis-and proliferation-related proteins,including Bax,Bcl-2,and c-Myc were detected by Western blot.Results TNMplot and R2 analysis demonstrated that both Pin1 and SREBP1 mRNA levels were significantly higher in cervical cancer tissues than in normal cervical tissues(P<0.05).Immunohistochemical staining indicated that Pin1 and SREBP1 expressions increased in cervical cancer tissues,and their expressions were positively correlated(r=0.652,P<0.05).Pin1 protein expression was the highest in cervical cancer SiHa cells(P<0.05).Compared with sh-NC group,the expression of Pin1 protein was significantly decreased in shPin1-A group and shPin1-B group(P<0.05),and the expression levels of Pin1,p-Akt,SREBP-1,c-Myc,and BCL-2 proteins were reduced(P<0.05),while the expression of Bax protein was elevated(P<0.05).Compared with sh-NC group,the cell proliferation was significantly inhibited in shPin1-A group and shPin1-B group(P<0.05),and the overall apoptosis rate was in-creased(P<0.05).Conclusion Downregulation of Pin1 can inhibit the proliferation of cervical cancer cells and induce the apoptosis via the Akt/SREBP1 axis,which suggests that Pin1 may be a potential molecular target for the treatment of cervical cancer.关键词
宫颈癌/Pin1/细胞增殖/细胞凋亡/Akt/SREBP1Key words
cervical cancer/Pin1/cell proliferation/cell apoptosis/Akt/SREBP1分类
医药卫生引用本文复制引用
严玉萍,肖金宝,美力班·吐尔逊,郭春凤,赵骏达,马俊旗..下调Pin1通过Akt/SREBP-1轴抑制宫颈癌细胞增殖[J].山西医科大学学报,2025,56(5):516-523,8.基金项目
国家自然科学基金资助项目(81960463) (81960463)