| First Author | Jariwala N | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 12 | Pages | 3306-3316 |
| PubMed ID | 28428278 | Mgi Jnum | J:242582 |
| Mgi Id | MGI:5905692 | Doi | 10.1158/0008-5472.CAN-17-0298 |
| Citation | Jariwala N, et al. (2017) Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma. Cancer Res 77(12):3306-3316 |
| abstractText | SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor-initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-kappaB signaling pathways in promoting TIC formation in Alb/SND1 mice. In human xenograft models of subcutaneous or orthotopic HCC, administration of the selective SND1 inhibitor 3', 5'-deoxythymidine bisphosphate (pdTp), inhibited tumor formation without effects on body weight or liver function. Our work establishes an oncogenic role for SND1 in promoting TIC formation and highlights pdTp as a highly selective SND1 inhibitor as a candidate therapeutic lead to treat advanced HCC. Cancer Res; 77(12); 3306-16. (c)2017 AACR. |
