PD46-12 SETD2-MEDIATED LOSS OF MIR-10B DETERMINES MAP4K4 ACTIVATION IN RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2018PD46-12 SETD2-MEDIATED LOSS OF MIR-10B DETERMINES MAP4K4 ACTIVATION IN RENAL CELL CARCINOMA libin Yan, heng Li, yucong Zhang, hua Xu, and zhangqun Ye libin Yanlibin Yan More articles by this author , heng Liheng Li More articles by this author , yucong Zhangyucong Zhang More articles by this author , hua Xuhua Xu More articles by this author , and zhangqun Yezhangqun Ye More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2160AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate the potential function and mechanism of SETD2/H3K36me3-miRNA-10b-MAPKs pathway in renal cell carcinoma(RCC). METHODS The expression level of miR-10b was evaluated through the meta-analysis of eligible studies reported miR-10b expression in multiple cancers and miRNA probe test in RCC tissue. The function of miR-10b and its down-stream molecular MAPKs was investigated in RCC cell lines via Transwell, MTS and EdU assays. The mechanism of SETD2-miR-10b-MAPKs was predicted by TCGA and Targetscan database. After knocking down SETD2 or miR-10b, this pathway was verified by chromatin immunoprecipitation(ChIP), luciferase assays et al. In the xenograft assay, three groups of Balb/c nude mices were treated with shSETD2, shSETD2+mimics-miR-10b and sh-LacZ in 786-O cell line, respectively. RESULTS SETD2 and miR-10b were downregulated in RCC. After up regulation of miR-10b by RNAi interference, the ability of proliferation, invasion and migration of RCC cells was suppressed. In addition, the result showed that the expression level of miR-10b was down-regulated after knock-down of SETD2. miR-10b can suppress the expression of MAP4K4,MAP3K7 and CDK6 directly and further influence phosphorylation of JNK. In xenograft assay, there was a dramatic decrease in tumor volume and weight in the shSETD2+mimics-miR-10b and sh-LacZ group compared with sh-SETD2 group. CONCLUSIONS miR-10b was the direct target of SETD2 and miR-10b can inhibit the expression of MAP4K4, MAP3K2 and MAP3K7, thus affecting the phosphorylation of JNK protein in MAPK signaling pathway and playing the role of tumor suppression; Targeting the SETD2/H3K36me3-miRNA-10b-MAPKs pathway might be an effective molecular targeted therapy to renal clear cell carcinoma. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e895-e896 Advertisement Copyright & Permissions© 2018MetricsAuthor Information libin Yan More articles by this author heng Li More articles by this author yucong Zhang More articles by this author hua Xu More articles by this author zhangqun Ye More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...