Overexpressed miR-183 promoted glioblastoma radioresistance via down-regulating LRIG1
Overexpressed miR-183 promoted glioblastoma radioresistance via down-regulating LRIG1
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过表达的miR-183通过下调LRIG1促进胶质母细胞瘤放射抗性
DOI：
10.1016/j.biopha.2017.11.050
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发表时间：
2018-01-01
影响因子：
7.5
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
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作者：
Fan, Hengyi;Yuan, Raorao;Zhang, Yan
背景：胶质瘤是癌症相关死亡的最常见原因。基于放疗的治疗似乎有效，而一些胶质母细胞瘤细胞的放射耐药性使治疗无效。因此，研究放射性耐药的潜在机制对胶质瘤的治疗至关重要。方法：利用x射线构筑耐辐射细胞。分别用CCK-8和Annexin-V/碘化丙啶（PI）检测细胞活力和凋亡。采用Real-time PCR和western blot检测基因表达。荧光素酶报告基因检测检测miR-183与LRIG1之间的关系。建立小鼠胶质瘤异种移植模型，检测miR-183在体内的作用。结果：miR-183在耐药组织中表达升高，LRIG1在敏感组织中表达降低。LRIG1在耐辐射胶质母细胞瘤细胞系U251R中的表达低于正常胶质母细胞瘤细胞系U251中的表达。过表达的miR-183抑制辐射耐药U251R细胞（U251R）的细胞凋亡。MiR-183靶向LRIG1调控其表达。转染miR-183 inhibitor的U251R细胞可促进LRIG1的表达，降低EFGR和p-Akt的表达，而共转染shRNA-LRIG1的U251R细胞可消除miR-183敲低的作用。转染miR-183 mimic的U251细胞降低了LRIG1的表达，促进了EFGR和p-Akt的表达，而共转染pcDNA-LRIG1的细胞则消除了miR-183过表达的影响。体内实验表明miR-183抑制剂抑制肿瘤生长，而miR-183 mimic促进肿瘤生长。结论：MiR-183过表达通过下调LRIG1和增加EFGR/Akt活性促进胶质母细胞瘤的放射抵抗。
Background: Glioma is the most common cause of cancer-related death. Therapy based on radiation seemed to effectively, while the radioresistance of several glioblastoma cells abolished the therapy. Thus, to employ the potential mechanism underlying the radioresistance is essential for glioma treatment.Methods: Radioresistant cells were constructed using the X-ray radiation. Cell viability and apoptosis were detect using CCK-8 and Annexin-V/propidium iodide (PI), respectively. Real-time PCR and western blot were performed to determine gene expression. Luciferase reporter assay was carried out to detect the relationship between miR-183 and LRIG1. Mice xenotransplant model of glioma was established to detect the role of miR-183 in vivo.Results: The expression of miR-183 was increased, while LRIG1 was decreased in resistant tissues rather than in sensitive tissues. The expression of LRIG1 was lower in radioresistant gliblastoma cell line U251R rather than in normal glioblastoma cell line U251. Overexpressed miR-183 suppressed cell apoptosis in radioresistance U251R cells (U251R). MiR-183 targets LRIG1 to regulate its expression. U251R cells transfected miR-183 inhibitor promoted the expression of LRIG1, and decreased the expression of EFGR and p-Akt, while U251R cells cotransfected with shRNA-LRIG1 abolished the effects of miR-183 knockdown. U251 cells transfected with miR-183 mimic decreased the expression of LRIG1, and promoted the expression of EFGR and p-Akt, while cells cotransfected with pcDNA-LRIG1 abolished the effects of miR-183 overexpression. In vivo experiments demonstrated that miR-183 inhibitor suppressed tumor growth, while miR-183 mimic promoted tumor growth.Conclusion: MiR-183 overexpression promoted radioresistance of glioblastoma via down-regulating LRIG1 and increasing the activity of EFGR/Akt.