Figure S4 from Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma
figure
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 SarkarQuantification of Western and IHC images
Funding
NCI
NIDDK
National Institute of Diabetes and Digestive and Kidney Diseases
NIH
History
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.Usage metrics
Categories
Licence
Exports
RefWorksRefWorks
BibTeXBibTeX
Ref. managerRef. manager
EndnoteEndnote
DataCiteDataCite
NLMNLM
DCDC