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学科主题临床医学
Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer
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
2015-03-30
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
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 ; 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
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
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 ; 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
引用统计
被引频次:24[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/400002259/57042
专题北京大学临床肿瘤学院_胃肠肿瘤中心
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
推荐引用方式
GB/T 7714
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.
APA Tao, Junyan.,Ji, Junfang.,Li, Xiaolei.,Ding, Ning.,Wu, Heng.,...&Cheng, Xin.(2015).Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer.ONCOTARGET,6(9),6977-6988.
MLA Tao, Junyan,et al."Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer".ONCOTARGET 6.9(2015):6977-6988.
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