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Figure S1 from Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma

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posted on 2023-03-31, 00:31 authored by Nidhi Jariwala, Devaraja Rajasekaran, Rachel G. Mendoza, Xue-Ning Shen, Ayesha Siddiq, Maaged A. Akiel, Chadia L. Robertson, Mark A. Subler, Jolene J. Windle, Paul B. Fisher, Arun J. Sanyal, Devanand Sarkar

Generation and characterization of Alb/SND1 mouse

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National Institute of Diabetes and Digestive and Kidney Diseases

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ARTICLE ABSTRACT

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-κB 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. ©2017 AACR.

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