title: MiR-136 targets E2F1 to reverse cisplatin chemosensitivity in glioma cells.
abstract: MicroRNAs (miRNAs) have gained much attention due to their critical roles in diverse biological events, including tumorigenesis. In this study, we demonstrate that miR-136 is down-regulated in two cohorts of patients with glioma. Furthermore, the low-level expression of miR-136 is significantly associated with a more aggressive and/or poor prognostic phenotype of patients with gliomas. Both gain- and loss-of-function experiments showed that miR-136 expression can reverse cisplatin resistance and enhance the response to cisplatin treatment. Furthermore, we identified a novel direct target of miR-136, the E2F transcription factor 1 (E2F1) oncogene. Depletion of E2F1 recapitulated the tumor-suppressive functions of miR-136, whereas re-expression of E2F1 attenuated the function of miR-136 in glioma cells. Finally, we revealed that miR-136 is inversely correlated with E2F1 expression in human glioma samples. The present study provides functional and mechanistic links between the tumor suppressor miR-136 and the oncogene E2F1 for the development of chemoresistance in human glioma. Our results indicate that targeting of the miR-136/E2F1 axis may provide a promising therapeutic approach to treat glioma.
authors.affiliation: Department of Neurosurgery, People's Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Wanghao
authors.initials: W
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Peisong
authors.initials: P
authors.lastname: Lu
authors.forename: Liping
authors.initials: L
authors.lastname: Zhan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.forename: Kan
authors.initials: K
authors.lastname: Cao
authors.forename: Qiaoyu
authors.initials: Q
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C577037:MIRN136 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D002945:Cisplatin