3 research outputs found
Notice of Retraction: Constructing innovative practical curriculum to develop students' practicability
No full textThe research of high-frequency phase shift and phase discrimination in a nanometer positioning system
No full textDistinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer
Get PDFDeregulation 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.NIH [R01CA136606]; UCSF Liver Center [P30DK026743]; University of Hawaii Cancer Center; NIDDK [R01 (1R01DK102601)]; Gilead Sciences Research Scholars Program; Minnesota Medical Foundation, NIH Clinical and Translational Science Award at the University of Minnesota [UL1TR000114]; China Scholarship Council [201306590021, 201206010086]; Intramural Research Program of the Center for Cancer Research, NCI [Z01 BC 010313]SCI(E)[email protected]; [email protected]
