The Effect Of MiR-365 On Radiosensitivity Of NSCLC Cells And Underlying Mechanisms

Radioresistance is a major challenge in lung cancer radiotherapy,and consequently,new radiosensitizers are urgently needed.MicroRNAs(miRNAs)have been demonstrated to participate in many important cellular processes including radiosensitization.MiR-365 is dysregulated in non-small cell lung cancer(NSCLC)and is able to restrain the development of NSCLC.However,the relationship between miR-365 and radiosensitivities of NSCLC cells remains largely unknown.Here we revealed that overexpression of miR-365 was able to enhance the radiosensitivity of NSCLC cells through targeting CDC25A.We found that the expression level of miR-365 was positively correlated with the radiosensitivity of NSCLC cell lines.Furthermore,our results showed that overexpression of miR-365 sensitized A549 cells to the y-rays.However,knockdown of miR-365 in H460 cells acted the converse manner.Mechanically,miR-365 was able to directly target 3;UTR of cell division cycle 25A(CDC25A)mRNA and reduced the expression of CDC25A at both levels of mRNA and protein.We confirmed that miR-365 increased the radiosensitivity of NSCLC cells by targeting CDC25A using in vitro and in vivo assays.Taken together,these results demonstrate that restoration of miR-365 expression enhances the radiosensitivity of NSCLC cells by suppressing CDC25A,and miR-365 may be used as a radiosensitizer for NSCLC therapy.Objective To explore the effects of(hepatitis B X-interacting protein)HBXIP down-regulation on the proliferation and radiosensitivity of cervical cancer ME-180 cells.Method According to the different treatment methods,cervical cancer ME-180 cells were divided into different groups:(1)The cervical cancer ME-180 cells were divided into 4 groups:control group,4 Gy ? ray irradiation group,HBXIP-siRNA transfection group and HBXIP-siRNA transfection+y ray irradiation group.Cervical cancer ME-180 cell proliferation was detected by MTT and clonogenic assays.The expression of Bcl-2 and Bid mRNA was detected by quantitative real-time polymerase chain reaction,and the phosphorylation of AKT protein was measured by Western blot analysis.(2)The cervical cancer ME-180 cells were divided into 3 groups:control group,HBXIP-siRNA transfection group and HBXIP-siRNA+AKT transfection group.Then the three groups of cells were irradiated with different doses of y ray,and the cervical cancer ME-180 cell proliferation was detected by clonogenic assay.Statistical significance of the results was determined by SPSS statistical software and analyzed by Student r-test.P<0.05 were considered statistically significant.Results MTT and clonogenic assays showed that,compared with the cells irradiated alone,the cervical cancer ME-180 cells irradiated in the presence of HBXIP-siRNA had significantly decreased proliferation(t=11.63,12.17,P<0.01).The decreased proliferation was accompanied by a decreased expression of Bcl-2 protein(t=10.88,P<0.01)and an increased expression of Bid protein(t=9.31,P<0.01).The transfection with HBXIP-siRNA inhibited the increased HBXIP protein expression and AKT phosphorylation,which were caused by radiation.The enhanced AKT expression significantly reduced the HBXIP-siRNA inhibition of cervical cancer ME-180 cell proliferation after irradiation as compared with that of the HBXIP-siRNA alone(t=8.96,P<0.01).Conclusion HBXIP down-regulation reduced the proliferation and increased the radiosensitivity of cervical cancer ME-180 cells by mediating AKT activation.