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学科主题: 临床医学
题名:
MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway
作者: 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
发表日期: 2015-04-01
DOI: 10.1080/15384101.2015.1007767
卷: 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
所属项目编号: 81372290 ; 81372291 ; RDB 2013-15
项目资助者: National Natural Science Foundation of China ; Peking University People&prime ; s Hospital Funds
WOS记录号: WOS:000352606600022
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67796
Appears in Collections:北京大学第二临床医学院_胃肠外科_期刊论文

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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

Recommended Citation:
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.
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