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IR@PKUHSC  > 北京大学临床肿瘤学院  > 胃肠肿瘤中心  > 期刊论文
学科主题: 临床医学
题名:
Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer
作者: Tao, Junyan1,2,3; Ji, Junfang4,5; Li, Xiaolei2,3,6; Ding, Ning2,3,7; Wu, Heng8; Liu, Yang2,3,6; Wang, XinWei4; Calvisi, Diego F.9; Song, Guisheng8; Cheng, Xin1,2,3
关键词: HCC ; c-Myc ; AKT ; Ras ; mouse liver cancer
刊名: ONCOTARGET
发表日期: 2015-03-30
卷: 6, 期:9, 页:6977-6988
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Cell Biology
研究领域[WOS]: Oncology ; Cell Biology
关键词[WOS]: HEPATOCELLULAR-CARCINOMA ; C-MYC ; TRANSGENIC MICE ; STEM-CELLS ; HEPATITIS ; SURVIVAL ; TUMORIGENICITY ; IDENTIFICATION ; AMPLIFICATION ; MANAGEMENT
英文摘要:

Deregulation of microRNAs (miRNAs) is a typical feature of human hepatocellular carcinoma (HCC). However, the in vivo relevance of miRNAs along hepatocarcinogenesis remains largely unknown. Here, we show that liver tumors induced in mice by c-Myc overexpression or AKT/Ras co-expression exhibit distinct miRNA expression profiles. Among the downregulated miRNAs, eight (miR-101, miR-107, miR-122, miR-29, miR365, miR-375, miR-378, and miR-802) were selected and their tumor suppressor activity was determined by overexpressing each of them together with c-Myc or AKT/Ras oncogenes in mouse livers via hydrodynamic transfection. The tumor suppressor activity of these microRNAs was extremely heterogeneous in c-Myc and AKT/Ras mice: while miR-378 had no tumor suppressor activity, miR-107, mir-122, miR-29, miR-365 and miR-802 exhibited weak to moderate tumor suppressor potential. Noticeably, miR-375 showed limited antineoplastic activity against c-Myc driven tumorigenesis, whereas it strongly inhibited AKT/Ras induced hepatocarcinogenesis. Furthermore, miR-101 significantly suppressed both c-Myc and AKT/Ras liver tumor development. Altogether, the present data demonstrate that different oncogenes induce distinct miRNA patterns, whose modulation differently affects hepatocarcinogenesis depending on the driving oncogenes. Finally, our findings support a strong tumor suppressor activity of miR-101 in liver cancer models regardless of the driver oncogenes involved, thus representing a promising therapeutic target in human HCC.

语种: 英语
所属项目编号: R01CA136606 ; P30DK026743 ; R01 (1R01DK102601) ; UL1TR000114 ; 201306590021 ; 201206010086 ; Z01 BC 010313
项目资助者: NIH ; UCSF Liver Center ; University of Hawaii Cancer Center ; NIDDK ; Gilead Sciences Research Scholars Program ; Minnesota Medical Foundation, NIH Clinical and Translational Science Award at the University of Minnesota ; China Scholarship Council ; Intramural Research Program of the Center for Cancer Research, NCI
WOS记录号: WOS:000352793800037
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57042
Appears in Collections:北京大学临床肿瘤学院_胃肠肿瘤中心_期刊论文

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作者单位: 1.Hubei Univ Chinese Med, Sch Pharm, Wuhan, Hubei, Peoples R China
2.Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA
3.Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA
4.NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA
5.Univ Hawaii Manoa, Univ Hawaii Canc Ctr, Canc Biol Program, Honolulu, HI 96822 USA
6.Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China
7.Peking Univ Canc Hosp & Inst, Dept Gastrointestinal Surg, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China
8.Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA
9.Ernst Moritz Arndt Univ Greifswald, Inst Pathol, Greifswald, Germany

Recommended Citation:
Tao, Junyan,Ji, Junfang,Li, Xiaolei,et al. Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer[J]. ONCOTARGET,2015,6(9):6977-6988.
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