CircYPEL2通过miR-498/MSMO1轴调节宫颈癌细胞的放射敏感性  

CircYPEL2 regulating radiosensitivity of cervical cancer cells through miR-498/MSMO1 axis

作　　者：王静[1] 易宣洪 汪萍[1] 黄晓智[1] 熊伟[1] WANG Jing;YI Xuanhong;WANG Ping;HUANG Xiaozhi;XIONG Wei(Tangshan Municipal People's Hospital,Hebei Tangshan 063000,China)

机构地区：[1]唐山市人民医院,河北唐山063000

出　　处：《中国妇幼健康研究》2023年第10期60-69,共10页Chinese Journal of Woman and Child Health Research

基　　金：河北省医学科学研究课题计划(20221823)。

摘　　要：目的研究环状RNA yippee样2(CircYPEL2)通过miR-498/甲基甾醇单加氧酶1(MSMO1)轴调节宫颈癌细胞放射敏感性的机制。方法检测人宫颈癌细胞株C33A及其放射线抵抗细胞C33A-RR中CircYPEL2、miR-498、MSMO1的表达。将体外培养的C33A-RR细胞随机分为对照组、放射组、放射+阴性对照组、放射+CircYPEL2敲低组、放射+CircYPEL2敲低+miR-498 inhibitor组,分组转染后,检测各组细胞CircYPEL2、miR-498及MSMO1的表达、增殖、凋亡及蛋白增殖细胞核抗原(PCNA)、细胞周期蛋白D1(CCND1)、B淋巴细胞瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)及天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)的表达。检测C33A-RR中CircYPEL2对miR-498的靶向调节与miR-498对MSMO1的靶向调节。结果与C33A细胞相比,C33A-RR细胞中CircYPEL2的表达、MSMO1 mRNA与蛋白表达升高(t值分别为-8.125、-11.600、-11.267,P<0.05),miR-498表达降低(t=8.104,P<0.05)。对照组、放射组、放射+阴性对照组、放射+CircYPEL2敲低组、放射+CircYPEL2敲低+miR-498 inhibitor组之间的CircYPEL2、miR-498、MSMO1 mRNA表达、MSMO1蛋白表达、细胞增殖率、集落生成率、凋亡细胞比例、细胞凋亡率比较差异均有统计学意义(F值分别为44.747、34.977、16.762、7.460、18.603、16.039、161.266、174.878,P<0.05);C33A-RR细胞增殖与凋亡相关蛋白表达比较,各组PCNA、CCND1、Bcl-2、Bax、caspase-3蛋白比较差异均有统计学意义(F值分别为15.777、13.693、81.133、78.133、51.587,P<0.05)。进一步比较发现,与对照组相比,放射组细胞各指标无明显变化(P>0.05);与对照组、放射组分别相比,放射+阴性对照组细胞各指标无明显变化(P>0.05);放射+CircYPEL2敲低组细胞增殖率、集落生成率、CircYPEL2表达、MSMO1 mRNA及蛋白表达、PCNA及CCND1、Bcl-2蛋白表达降低(P<0.05),凋亡细胞比例、细胞凋亡率、miR-498表达、Bax及caspase-3蛋白表达升高(P<0.05)。miR-498 inhibitor可减弱CircYPEL2敲低对放射下细�Objective To explore mechanisms that circular RNA yippee like 2(CircYPEL2)regulates radiosensitivity of cervical cancer cells through miR-498/methylsterol monooxygenase 1(MSMO1)axis.Methods The expressions of CircYPEL2,miR-498 and MSMO1 in human cervical cancer cell line C33A and its radiation resistant cell line C33A-RR were detected.C33A-RR cells cultured in vitro were randomly divided into control group,radiation group,radiation+negative control group,radiation+CircYPEL2 knockdown group,and radiation+CircYPEL2 knockdown+miR-498 inhibitor group.After grouping transfections,the expression,proliferation and apoptosis of CircYPEL2,miR-498 and MSMO1,and the expressions of such proteins as proliferating cell nuclear antigen(PCNA),cyclin D1(CCND1),B-cell lymphoma-2(Bcl-2),BCL2-associated X protein(Bax),cysteine-containing aspartate-specific proteases 3(caspase-3)of C33A-RR cells in the five groups were detected.Also,the targeted regulation of CircYPEL2 on miR-498 and the targeted regulation of miR-498 on MSMO1 in C33A-RR cells were detected.Results Compared with C33A cells,the expression of CircYPEL2,and the expressions of mRNA and proteins of MSMO1 in C33A-RR cells increased(t=-8.125,-11.600 and-11.267 respectively,all P<0.05),while the expression of miR-498 decreased(t=8.104,P<0.05).Among the five groups,there were significant differences in the expressions of CircYPEL2,miR-498 and MSMO1 mRNA,MSMO1 proteins,cell proliferation rate,colony forming efficiency,and percentage of apoptotic cells,apoptosis rate(F=44.747,34.977,16.762,7.460,18.603,16.039,161.266 and 174.878 respectively,all P<0.05).In expressions of PCNA,CCND1,Bcl-2,Bax,caspase-3,there were significant differences among the five groups(F=15.777,13.693,81.133,78.133 and 51.587 respectively,all P<0.05).Further comparison shown that as compared with the control group,the all cell indicators in the radiation group didn't change significantly(all P>0.05).The cell proliferation rate,colony forming efficiency,and expressions of CircYPEL2,MSMO1 mRNA and proteins,P

关 键 词：环状RNA yippee样2 miR-498/甲基甾醇单加氧酶1 宫颈癌 放射敏感性 

分 类 号：R173[医药卫生—妇幼卫生保健]