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长链非编码RNA LINC00152对人脑胶质瘤裸鼠移植瘤生长的影响及机制探讨 被引量:3

Effect of long noncoding RNA LINC00152 on the growth of human glioma xenografts in nude mice and its mechanism
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摘要 目的 观察长链非编码RNA(long noncoding RNA,LncRNA) LINC00152过表达对人脑胶质瘤U251荷瘤鼠肿瘤生长的影响并对其机制进行探讨。方法 慢病毒转染法上调U251细胞LINC00152表达水平,设立LINC00152过表达组(LV-LINC00152组)和空载对照组(LV组)细胞,以正常U251细胞作为空白对照组(control组);qRT-PCR检测LINC00152表达水平;构建U251荷瘤鼠模型,p-YAP抑制剂XMU-MP-1进行处理,测量肿瘤体积,实验终点称量瘤重;免疫组织化学染色观察肿瘤组织Ki67表达;蛋白印记实验检测YAP、p-YAP、LATS1、pLATS1蛋白表达。结果 与LV组相比,LV-LINC00152组LINC00152表达明显上调(P<0. 01)。实验终点时,与LV组荷瘤鼠肿瘤相比,LV-LINC00152组肿瘤体积显著增大,瘤重明显增加(P<0. 01);XMU-MP-1(1 mg/kg和3 mg/kg)处理明显降低LV-LINC00152组荷瘤鼠肿瘤体积和瘤重(P<0. 01),并呈剂量依赖性。LV组肿瘤组织Ki67呈弱阳性表达,而LV-LINC00152组呈强阳性表达;XMU-MP-1(1 mg/kg和3 mg/kg)处理后二者肿瘤组织Ki67呈弱阳性和阳性。与LV组相比,LV-LINC00152组肿瘤组织p-YAP和p-LATS1蛋白表达明显上调(P<0. 01);XMU-MP-1(1 mg/kg和3 mg/kg)处理可逆转p-YAP和p-LATS1蛋白表达(P<0. 01),并存在剂量依赖性。结论 长链非编码RNA LINC00152可诱导YAP磷酸化,促进脑胶质瘤生长,而p-YAP抑制剂XMU-MP-1能抑制长链非编码RNA LINC00152的上述生物学效应。 Objective To observe the effect of overexpression of a long noncoding RNA(LncRNA)LINC00152 on the tumor growth of human glioma U251 tumor-bearing mice and to explore its related mechanisms.Methods Lentiviral transfection upregulated the expression of LINC00152 in U251 cells.LINC00152 overexpression(LV-LINC00152 group)and empty control(LV group)cells were established,and normal U251 cells were used as the blank group(Control group).qRT-PCR was used to detect the expression of LINC00152.A U251 tumor-bearing mouse model was established.The p-YAP inhibitor XMU-MP-1 was administered to mice and the tumor volume was measured and the tumor weight was weighed at the end of the experiment.Immunohistochemical staining was used to observe the expression of Ki67 in tumor tissues.The expressions of YAP,p-YAP,LATS1 and p-LATS1 proteins were detected by Western blotting.Results Compared with the LV group,the expression of LINC00152 in the LV-LINC00152 group was significantly upregulated(P<0.01).End of experiment,compared with the LV tumor-bearing mice,the tumor volume and tumor weight in the LVLINC00152 group were increased significantly(P<0.01).XMU-MP-1(1 and 3 mg/kg)treatment significantly reduced the tumor volume and tumor weight of LV-LINC00152 tumor-bearing mice in a dose-dependent manner(P<0.01).Ki67 staining in the LV group was weakly positive but strongly positive in the LV-LINC00152 group.After XMU-MP-1(1 and 3 mg/kg)treatment,Ki67 was weakly positive in the tumor tissues of the LV-LINC0015 group.Compared with the LV group,the expression of p-YAP and p-LATS1 protein in the LV-LINC00152 group was significantly upregulated(P<0.01),and XMU-MP-1(1 and 3 mg/kg)treatment reversed the p-YAP and p-LATS1 protein expression(P<0.01).Conclusions The long noncoding RNA LINC00152 induces YAP phosphorylation to promote glioma growth,while the p-YAP inhibitor XMU-MP-1 inhibits the above biological effects of the long noncoding RNA LINC00152.
作者 金亮 金爱 赵立智 JIN Liang;JIN Ai;ZHAO Lizhi(Department of Neurosurgery,Cangzhou People’s Hospital,Cangzhou 061000,China;Department of Hematology,Cangzhou People’s Hospital,Cangzhou 061000)
出处 《中国比较医学杂志》 CAS 北大核心 2019年第11期28-33,49,共7页 Chinese Journal of Comparative Medicine
基金 2018年沧州市科技计划项目(183302129) 2016年沧州市科技计划项目(162302072)
关键词 长链非编码RNA(LncRNA) LINC00152 脑胶质瘤 生长 YAP蛋白 裸鼠 long noncoding RNA(LncRNA) LINC00152 glioma growth YAP protein nude mouse
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