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Σάββατο 2 Σεπτεμβρίου 2017

MicroRNA-1179 inhibits glioblastoma cell proliferation and cell cycle progression via directly targeting E2F transcription factor 5.

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MicroRNA-1179 inhibits glioblastoma cell proliferation and cell cycle progression via directly targeting E2F transcription factor 5.

Am J Cancer Res. 2017;7(8):1680-1692

Authors: Xu X, Cai N, Zhi T, Bao Z, Wang D, Liu Y, Jiang K, Fan L, Ji J, Liu N

Abstract
Glioblastoma multiforme (GBM) is an extraordinary aggressive disease that requires more effective therapeutic options. In the past few years, many microRNAs (miRNAs) have been demonstrated to have important roles in promoting GBM progression. However, little is known about the role of miR-1179 in GBM. In the present study, we found that miR-1179 was significantly downregulated in glioma tissues and cell lines. Functional experiments showed that introduction of miR-1179 dramatically suppressed GBM cell proliferation and cell cycle progression. Importantly, treatment of miR-1179 strongly inhibited tumor growth in a subcutaneous GBM model. Further studies showed that E2F transcription factor 5 (E2F5), a key transcription factor that controls cell cycle transition, was a direct target of miR-1179. Silencing of E2F5 inhibited the proliferative ability of GBM cells and induces cell cycle arrest, which were consistent with the effects of miR-1179 overexpression. More importantly, reintroduction of E2F5 into GBM cells reversed the tumor-suppressive function of miR-1179. Finally, we demonstrated that miR-1179 expression was negatively correlated with E2F5 messenger RNA (mRNA) levels in high-grade gliomas. Our findings provide new insights into the role of miR-1179 in the progression of GBM, and implicate the potential application of miR-1179 in GBM therapy.

PMID: 28861324 [PubMed]



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2x05rb9

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