微小RNA-151a-3p对非小细胞肺癌放疗敏感性的影响及其分子机制  

Effect of microRNA-151a-3p on radiosensitivity of non-small cell lung cancer and its molecular mechanism

作　　者：孙永臣[1] 王晓朦 祖鹏 刘阳[1] 韩文杰[2] Sun Yongchen;Wang Xiaomeng;Zu Peng;Liu Yang;Han Wenjie(Department of Radiation Oncology,the First People’s Hospital of Shangqiu(Clinical College,Xuzhou Medical University),Shangqiu 476100,China;Department of Oncology,the First People’s Hospital of Shangqiu(Clinical College,Xuzhou Medical University),Shangqiu 476100,China)

机构地区：[1]商丘市第一人民医院(徐州医科大学临床学院)肿瘤放疗二科,商丘476100 [2]商丘市第一人民医院(徐州医科大学临床学院)肿瘤综合科,商丘476100

出　　处：《中华实验外科杂志》2024年第11期2542-2546,共5页Chinese Journal of Experimental Surgery

基　　金：吴阶平医学基金会项目(320.6750.2023-02-1)。

摘　　要：目的:探讨微小RNA(miR)-151a-3p对非小细胞肺癌放疗敏感性的影响及其分子机制。方法:选取2018年12月至2023年1月我院收治的65例三维适形调强放疗的肺癌样本和癌旁组织作为研究对象,采用荧光定量PCR分析检测放疗敏感组和耐受组肺癌组织中miR-151a-3p的表达水平;人非小细胞肺癌细胞A549分为对照组、miR-151a-3p组和miR-151a-3p抑制剂组,采用miRNA对照、miR-151a-3p模拟物和miR-151a-3p抑制剂转染至细胞,72 h后,分别采用6 MV-X线(6 Gy)照射细胞,采用细胞计数试剂盒(CCK-8)和克隆形成实验分析细胞的增殖能力;采用细胞凋亡检测试剂盒测定细胞的凋亡能力;建立移植瘤裸鼠模型,放疗治疗后,测定肿瘤体积,采用原位缺口末端标记法(TUNEL)染色分析小鼠肿瘤组织细胞凋亡情况,采用蛋白质免疫印迹分析小鼠肿瘤组织组蛋白2A变异体(H2AX)的表达水平。组间比较采用独立样本 t检验。 结果:三维适形调强放疗敏感肺癌组织miR-151a-3p表达水平(1.53±0.09)低于耐受组织(1.75±0.11),差异有统计学意义( t=9.162, P<0.05)。miR-151a-3p组细胞CCK-8吸光度值和细胞克隆形成数量[0.84±0.04、(69.14±5.40)个]低于对照组[1.32±0.06、(107.42±11.01)个],差异有统计学意义( t=18.080、8.259, P<0.05)。miR-151a-3p抑制剂组细胞CCK-8吸光度值和细胞克隆形成数量[1.77±0.14、(142.14±10.51)个]高于对照组[1.32±0.06、(107.42±11.01)个],差异有统计学意义( t=7.797、6.033, P<0.05)。miR-151a-3p组细胞凋亡比例[(55.29±7.87)%]高于对照组[(38.93±4.42)%],差异有统计学意义( t=4.792, P<0.05)。miR-151a-3p抑制剂组细胞凋亡率[(22.31±11.01)%]低于对照组[(38.93±4.42)%],差异有统计学意义( t=8.513, P<0.05)。miR-151a-3p组细胞成瘤体积[(455.31±42.05) mm 3]低于对照组[(638.57±36.59) mm 3],差异有统计学意义( t=8.698, P<0.05)。miR-151a-3p抑制剂组细胞成瘤体积[(856.87±27.54) mm 3]高于对照组[(638.57±36.59) mm 3],�Objective To investigate the effect of microRNA(miRNA,miR)-151a-3p on radiotherapy sensitivity of non-small cell lung cancer and its molecular mechanism.Methods 65 cases of lung cancer samples and adjacent tissues after three-dimensional conformal radiotherapy in our hospital from December 2018 to January 2023 were selected as the research object.The expression levels of miR-151a-3p in lung cancer tissues of the radiotherapy sensitive group and the radiotherapy tolerant group were detected by fluorescence quantitative PCR analysis.Human non-small cell lung cancer A549 cells were divided into control group,miR-151a-3pgroup and miR-151a-3p inhibitor group.The cells were transfected with miRNA control,miR-151a-3p mimics and miR-151a-3p inhibitors.After 72 h,the cells were irradiated with 6 MV x-ray(6 Gy),and the proliferation ability was analyzed by cell counting kit-8(CCK-8)and clonogenic assay.The apoptotic ability of cells was determined by apoptosis detection kit.The nude mouse model of transplanted tumor was established.After radiotherapy,the tumor volume was measured,the apoptosis of tumor tissues was analyzed by terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining,and the expression level of histone family 2A variant(H2AX)in tumor tissues was analyzed by Western blotting.The measurement data between groups were compared by independent sample t test.ResultsThe expression level of miR-151a-3p in three-dimensional conformal radiotherapy sensitive lung cancer tissues(1.53±0.09)was significantly lower than that in tolerant tissues(1.75±0.11,t=9.162,P<0.05).The absorbance value of CCK-8 and the number of cell clones in miR-151a-3p group[0.84±0.04,(69.14±5.40)cells]were significantly lower than that in control group[1.32±0.06,(107.42±11.01)cells,t=18.080,8.259,P<0.05].The absorbance value of CCK-8 and the number of cell clones in the miR-151a-3p inhibitor group[1.77±0.14,(142.14±10.51)cells]were significantly higher than those in the control group[1.32±0.06,(107.42±11.01)cells,t=

关 键 词：非小细胞肺癌 微小RNA-151a-3p 放疗敏感性 

分 类 号：R734.2[医药卫生—肿瘤]