| Wang Pengfei,Li Wenhan,Hong Shunming,et al.miR-221/222 enhances radiation resistance of glioblastoma by Akt pathway[J].Chinese Journal of Radiological Medicine and Protection,2015,35(3):177-182 |
| miR-221/222 enhances radiation resistance of glioblastoma by Akt pathway |
| Received:March 29, 2014 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.03.004 |
| KeyWords:Glioblastoma Radiation resistance MiR-221/222 DNA damage Akt |
| FundProject:天津市自然科学基金 (13JCYBJC21700);天津市卫生局公关项目(12KG113) |
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| 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 also increased(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. |
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