miR-221/222 enhances radiation resistance of glioblastoma by Akt pathway
10.3760/cma.j.issn.0254-5098.2015.03.004
- VernacularTitle:miR-221/222激活Akt通路增加恶性胶质瘤的放射抗性
- Author:
Pengfei WANG
;
Wenhan LI
;
Shunming HONG
;
Chunzhi ZHANG
- Publication Type:Journal Article
- Keywords:
Glioblastoma;
Radiation resistance;
MiR-221/222;
DNA damage;
Akt
- From:
Chinese Journal of Radiological Medicine and Protection
2015;35(3):177-182
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the pathway of miR-221/222 in enhancing radiation resistance of glioblastoma.Methods After 2 Gy of X-ray irradiation,the expressions of miR-221/222 in U251,U87 and LN229 glioblastma cells were detected with real-time PCR.Clonogenic assay was used to measure the radiosensitivity of glioblastoma after knocking down miR-221/222.ChIP assay was used to identify the combination situation of c-jun and miR-221/222.Luciferase assay was applied to check whether PTEN was a target of miR-221/222.Western blot was used to detect the expression of relevant proteins in the glioblastoma cells after knocking down miR-221/222.The effect of miR-221/222 and irradiation on growth of glioblastoma in nude mice was also observed.Results The expression of miR-221/222 was increased by irradiation(t =5.48 ～29.21,P ＜ 0.05) and the radiosensitivity of anti-miR-221/222-transfected cells was alsoincreased(F=1 202.22,1 789.12,1 012.32,P＜0.05).MiR-221/ 222 was transcriptionally regulated by c-jun with a target of PTEN (t =13.16,P ＜ 0.05).When miR-221/222 was knocked-down,the expression of pAkt and DNA-PKcs were down-regulated while PTEN and GSK-3β were up-regulated,and the expression of Akt were not changed.Moreover,the growth of xenograft tumor was significantly inhibited by the combination treatment of anti-miR-221/222 and irradiation(F =56.36,P ＜ 0.05).Conclusions The expression of miR-221/222 in glioblastoma cells can be increased by irradiation,and the activation of Akt pathway downstream miR-221/222 could enhance the radiation resistance of glioblastoma.
