Effect of microRNA-151a-3p on radiosensitivity of non-small cell lung cancer and its molecular mechanism
Objective To investigate the effect of microRNA(miRNA,miR)-151a-3p on radio-therapy 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 miR-NA 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 clono-genic assay.The apoptotic ability of cells was determined by apoptosis detection kit.The nude mouse mod-el 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 an-alyzed by Western blotting.The measurement data between groups were compared by independent sample t test.Results The 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 significant-ly higher than those in the control group[1.32±0.06,(107.42±11.01)cells,t=7.797,6.033,P<0.05].The proportion of apoptosis in the miR-151a-3p group[(55.29±7.87)%]was significantly higher than that in the control group[(38.93±4.42)%,t=4.792,P<0.05].The apoptosis rate of miR-151a-3p inhibitor group[(22.31±11.01)%]was significantly lower than that of the control group[(38.93±4.42)%,t=8.513,P<0.05].The tumor forming volume of miR-151a-3p group[(455.31±42.05)mm3]was significantly lower than that of the control group[(638.57±36.59)mm3,t=8.698,P<0.05].The tumor forming volume of miR-151a-3p inhibitor group[(855.31±42.05)mm3]was sig-nificantly higher than that of the control group[(638.57±36.59)mm3,t=12.610,P<0.05].The ex-pression level of H2AX in miR-151a-3p group(0.70±0.07,0.54±0.10)was significantly lower than that in the control group(0.96±0.07,0.79±0.15,t=6.783,3.609,P<0.05).The expression level of H2AX in cells and tumor tissues of miR-151a-3p inhibitor group(1.66±0.12,1.37±0.13)was sig-nificantly higher than that in tumor tissues of control group(0.96±0.07,0.79±0.15,t=13.190,7.576,P<0.05).Conclusion MiR-151a-3p is highly expressed in non-small cell lung cancer,and its high expression reduces radiotherapy sensitivity,mainly through H2AX.
Non small cell lung cancerMicroRNA-151a-3pRadiotherapy sensitivity