Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer.
Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer.
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DOI:
10.18632/oncotarget.3166
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发表时间:
2015-03-30
期刊:
影响因子:
--
通讯作者:
Chen X
中科院分区:
文献类型:
--
作者:
Tao J;Ji J;Li X;Ding N;Wu H;Liu Y;Wang XW;Calvisi DF;Song G;Chen X
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, miR-365, 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.
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影响因子:
29.4
作者:
El-Serag HB
通讯作者:
El-Serag HB
影响因子:
11.2
作者:
Cao Z;Fan-Minogue H;Bellovin DI;Yevtodiyenko A;Arzeno J;Yang Q;Gambhir SS;Felsher DW
通讯作者:
Felsher DW
影响因子:
5.8
作者:
Kane, Robert C.;Farrell, Ann T.;Pazdur, Richard
通讯作者:
Pazdur, Richard
影响因子:
158.5
作者:
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者:
Bruix, Jordi
DOI:
10.1056/nejmoa0901282
发表时间:
2009-10-08
期刊:
The New England journal of medicine
影响因子:
--
作者:
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
通讯作者:
Wang XW