title: Let-7b overexpression leads to increased radiosensitivity of uveal melanoma cells.
abstract: Uveal melanoma (UM) is an intraocular malignant tumor in adults that is characterized by rapid progression and recurrence. Irradiation has become the primary therapy for UM patients who are not candidates for surgery. However, after large-dose fraction irradiation treatment, some patients undergo subsequent enucleation because of radiotherapy-related complications. This situation has raised concerns on how to optimize the effectiveness of radiation treatment. Recent investigations of microRNAs are changing our understanding of UM tumor biology and are helping to identify novel targets for radiotherapy. The radioresistant UM cell lines OM431 and OCM1 were selected and exposed to irradiation, and let-7b was found to be downregulated after exposure. We then confirmed that let-7b mimics could inhibit UM growth both in vitro and in vivo. More specifically, transfection with let-7b mimics markedly resensitized OCM1 and OM431 cells to irradiation by reducing the population of S-phase cells. Cyclin D1 plays a vital role in cell cycle arrest, which is induced by let-7b overexpression. Cyclin D1 is also a target of let-7b and its expression is suppressed by upregulation of let-7b. Collectively, our results indicate that let-7b overexpression can in turn downregulate cyclin D1 expression and enhance the radiosensitivity of UM through cell cycle arrest. Let-7b could serve as a marker for radiosensitivity and could enhance the therapeutic benefit of UM cell irradiation.
authors.affiliation: aDepartment of Ophthalmology, Ninth People's Hospital bDepartment of Radiation Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jiayan
authors.initials: J
authors.lastname: Fan
authors.forename: Renbin
authors.initials: R
authors.lastname: Jia
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xu
authors.forename: Liyan
authors.initials: L
authors.lastname: Dai
authors.forename: Ai
authors.initials: A
authors.lastname: Zhuang
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000528:radiation effects; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000528:radiation effects; D015854:Up-Regulation; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D023041:Xenograft Model Antitumor Assays; D000098943:Uveal Melanoma
chemical_list: C530104:CCND1 protein, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D019938:Cyclin D1