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学科主题临床医学
MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway
Wang, Bo1; Shen, Zhan-long1; Gao, Zhi-dong1; Zhao, Gang2; Wang, Chun-you2; Yang, Yang1; Zhang, Ji-zhun1; Yan, Yi-chao1; Shen, Chao1; Jiang, Ke-wei1; Ye, Ying-jiang1; Wang, Shan1
关键词apoptosis c-Jun colorectal cancer miR-194 MAP4K4 MDM2 proliferation
刊名CELL CYCLE
2015-04-01
DOI10.1080/15384101.2015.1007767
14期:7页:1046-1058
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]C-JUN ; GASTRIC-CANCER ; MESSENGER-RNA ; COLON-CANCER ; KAPPA-B ; EXPRESSION ; MDM2 ; MICRORNA ; CELLS ; P53
英文摘要

Tumor growth cascade is a complicated and multistep process with numerous obstacles. Until recently, evidences have shown the involvement of microRNAs (miRNAs) in tumorigenesis and tumor progression of various cancers, including colorectal cancer (CRC). In this study, we explored the role of miR-194 and its downstream pathway in CRC. We acquired data through miRNA microarray profiles, showing that the expression of miR-194 was significantly suppressed in CRC tissues compared with corresponding noncancerous tissues. Decreased miR-194 expression was obviously associated with tumor size and tumor differentiation, as well as TNM stage. Both Kaplan-Meier and multivariate survival analysis showed that downregulated miR-194 was associated with overall survival. Moreover, functional assays indicated that overexpression of miR-194 in CRC cell lines inhibited cell proliferation both in vitro and in vivo. In addition, using dual-luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194. Silencing of MAP4K4 resulted in similar biological behavior changes to that of overexpression of miR-194. We also observed through Human Gene Expression Array that MDM2 was one of the downstream targets of MAP4K4. Knockdown of MAP4K4 downregulated MDM2 expression through transcription factor c-Jun binding to the -1063 to -1057 bp of the promoter. These results suggest that miR-194, regulating the MAP4K4/c-Jun/MDM2 signaling pathway, might act as a tumor suppressor and serve as a novel target for CRC prevention and therapy.

语种英语
WOS记录号WOS:000352606600022
项目编号81372290 ; 81372291 ; RDB 2013-15
资助机构National Natural Science Foundation of China ; Peking University People&prime ; s Hospital Funds
引用统计
被引频次:31[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67796
专题北京大学第一临床医学院_皮肤性病科
北京大学第二临床医学院_胃肠外科
作者单位1.Peking Univ Peoples Hosp, Dept Surg Gastroenterol, Beijing, Peoples R China
2.Huazhong Univ Sci & Technol, Pancreat Dis Inst, Union Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China
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Wang, Bo,Shen, Zhan-long,Gao, Zhi-dong,et al. MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway[J]. CELL CYCLE,2015,14(7):1046-1058.
APA Wang, Bo.,Shen, Zhan-long.,Gao, Zhi-dong.,Zhao, Gang.,Wang, Chun-you.,...&Wang, Shan.(2015).MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway.CELL CYCLE,14(7),1046-1058.
MLA Wang, Bo,et al."MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway".CELL CYCLE 14.7(2015):1046-1058.
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