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目的:探讨长链非编码(lnc)RNA HCP5对胶质瘤细胞的辐射敏感性的影响及其机制。方法:分别用0、2、4、6、8 Gy射线照射胶质瘤细胞U251和U87，作为不同剂量辐射组；将si-con、si-HCP5、pcDNA、pcDNA-HCP5转染至细胞U251和U87中，分别记为si-con组、si-HCP5组、pcDNA组、pcDNA-HCP5组；将si-con、si-HCP5转染至细胞U251和U87后再用4 Gy射线照射，分别记为IR＋si-con组、IR＋si-HCP5组，仅用4 Gy射线照射的细胞记为IR组；将si-HCP5分别与anti-miR-con、anti-miR-508-3p共转染至细胞U251和U87后再用4 Gy射线照射，分别记为IR＋si-HCP5＋anti-miR-con组、IR＋si-HCP5＋anti-miR-508-3p组，转染均用脂质体法。采用RT-qPCR检测miR-508-3p和HCP5的表达；细胞克隆形成实验检测胶质瘤细胞的放射敏感性；流式细胞术检测细胞凋亡；Western blot检测磷酸化H2AX(γ-H2AX)、裂解半胱氨酸天冬氨酸蛋白酶-3(Cleaved caspase-3)、磷酸化磷脂酰肌醇3激酶(p-PI3K)、磷脂酰肌醇3激酶(PI3K)、磷酸化蛋白激酶B(p-AKT)、蛋白激酶B(AKT)蛋白表达；双荧光素酶报告基因检测实验检测荧光活性。结果:放射处理的胶质瘤细胞HCP5高表达，miR-508-3p低表达；沉默HCP5后细胞U251和U87放射敏感性增强，细胞凋亡率升高[U251：(16.67±1.68)%，(3.58±0.62)%，n t＝21.929，n P<0.05；U251：(12.32±1.08)%，(4.48±0.71)%，n t＝18.198，n P<0.05]，γ-H2AX[U251：(0.45±0.04)，(0.23±0.05)，n t＝10.307，n P<0.05；U87：(0.38±0.04)，(0.24±0.03)，n t＝8.400，n P<0.05]、Cleaved caspase-3[U251：(0.37±0.04)，(0.16±0.03)，n t＝12.600，n P<0.05；U87：(0.38±0.04)，(0.22±0.03)，n t＝9.600，n P<0.05]表达水平升高。相比单独沉默HCP5或辐射处理，沉默HCP5同时辐射处理U251细胞，细胞凋亡率[(25.34±1.54)%，(16.67±1.68)%，n t＝11.413，n P<0.05；(25.34±1.54)，(11.13±1.06)，n t＝22.802，n P<0.05]显著升高，γ-H2AX[(0.69±0.05)，(0.45±0.04)，n t＝11.245，n P<0.05；(0.69±0.05)，(0.31±0.04)，n t＝17.804，n P<0.05]、Cleaved caspase-3[(0.52±0.06)，(0.37±0.04)，n t＝6.240，n P<0.05；(0.52±0.06)，(0.34±0.04)，n t＝7.488，n P<0.05]表达水平升高。辐射处理后且沉默HCP5后U251和U87细胞中p-PI3K[(0.21±0.02)，(0.52±0.04)，n t＝20.795，n P<0.05；(0.26±0.23)，(0.67±0.07)，n t＝5.116，n P<0.05]、p-AKT[(0.22±0.03)，(0.66±0.07)，n t＝17.332，n P<0.05；(0.23±0.04)，(0.71±0.03)，n t＝28.800，n P<0.05]表达水平降低。HCP5可靶向调节miR-508-3p表达；干扰miR-508-3p逆转了沉默HCP5和辐射对U251和U87细胞放射的增敏和促进细胞凋亡的作用，降低了γ-H2AX、Cleaved caspase-3表达水平，提高了p-PI3K、p-AKT表达水平。n 结论:沉默lncRNA HCP5可增强胶质瘤细胞的辐射敏感性，促进细胞凋亡，其机制可能与miR-508-3p及PI3K/Akt信号通路有关，可为胶质瘤治疗提供新靶点和新思路。“,”Objective:To investigate the effect of long non-coding (lnc) RNA HCP5 on the radiation sensitivity of glioma cells and underlying mechanism.Methods:The glioma cells U251 and U87 were irradiated with 0, 2, 4, 6, and 8 Gy rays as different doses.si-Con, si-HCP5, pcDNA, and pcDNA-HCP5 were transfected into cells U251 and U87, recorded as si-con group, si-HCP5 group, pcDNA group, and pcDNA-HCP5 group.si-Con and si-HCP5 were transfected into cells U251 and U87, and then irradiated with 4 Gy rays, respectively, recorded as IR+ si-con group and IR+ si-HCP5 group, the cells only irradiated with 4 Gy rays were recorded as IR group.After si-HCP5 with anti-miR-con and anti-miR-508-3p was co-transfected into cell U251 and U87, respectively, irradiated with 4 Gy rays, recorded as IR+ si-HCP5+ anti-miR-con group and IR+ si-HCP5+ anti-miR-508-3p group, respectively, the transfection was performed by liposome method.RT-qPCR was used to detect the expression of miR-508-3p and HCP5.Cell clone formation assay was used to detect the radiosensitivity of glioma cells.Flow cytometry was used to detect apoptosis, dual luciferase Reporter gene detection experiments detects fluorescence activity.Results:HCP5 was highly expressed in radiation-treated glioma cells, and miR-508-3p was lowly expressed.After silenced HCP5, U251 and U87 cells had enhanced radiosensitivity and apoptotic rate((16.67±1.68) n vs (3.58±0.62), n t=21.929, n P<0.05; (12.32±1.08)n vs (4.48±0.71), n t=18.198, n P<0.05) was increased, and γ-H2AX( (0.45±0.04)n vs (0.23±0.05), n t=10.307, n P<0.05; (0.38±0.04)n vs (0.24±0.03), n t=8.400, n P<0.05), Cleaved caspase-3((0.37±0.04)n vs (0.16±0.03), n t=12.600, n P<0.05; (0.38±0.04)n vs (0.22±0.03), n t=9.600, n P<0.05) expressions were increased.Compared with silencing HCP5 or radiation treatment alone, silencing HCP5 and radiation treatment of U251 cells simultaneously, the apoptosis rate ((25.34±1.54)n vs (16.67±1.68), n t=11.413, n P<0.05; (25.34±1.54)n vs (11.13±1.06), n t=22.802, n P<0.05) was significantly increased, and γ-H2AX((0.69±0.05)n vs (0.45±0.04), n t=11.245, n P<0.05; (0.69±0.05)n vs (0.31±0.04), n t=17.804, n P<0.05), Cleaved caspase-3 ((0.52±0.06/0.37±0.04,n t=6.240, n P<0.05) (0.52±0.06/0.34±0.04,n t=7.488, n P<0.05) expressions were increased.The expressions of p-PI3K ((0.21±0.02)n vs (0.52±0.04), n t=20.795, n P<0.05; (0.26±0.23 ), ( 0.67±0.07),n t=5.116, n P<0.05), p- AKT ((0.22±0.03)n vs (0.66±0.07), n t=17.332, n P<0.05; (0.23±0.04)n vs (0.71±0.03), n t=28.800, n P<0.05) in U251 and U87 cells were decreased.HCP5 can target the regulation of miR-508-3p expression; interfering with miR-508-3p reversed the effects of silent HCP5 and radiation on the radiation sensitization and apoptosis of U251 and U87 cells.It reduced the expression levels of reducing γ-H2AX and Cleaved caspase-3, while increased the expression levels of p-PI3K and p-AKT.n Conclusion:Silencing lncRNA HCP5 can enhance the radiation sensitivity of glioma cells and promote apoptosis.The mechanism may be related with the miR-508-3p and PI3K/Akt signaling pathway, which will provide new targets and new ideas for glioma treatment.