2. Academic Validation
  3. Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma

Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma

  • Cancer Res. 2017 Jun 15;77(12):3306-3316. doi: 10.1158/0008-5472.CAN-17-0298.
Nidhi Jariwala 1,  Devaraja Rajasekaran 1,  Rachel G Mendoza 1,  Xue-Ning Shen 1,  Ayesha Siddiq 1,  Maaged A Akiel 1,  Chadia L Robertson 1,  Mark A Subler 1,  Jolene J Windle 1,  Paul B Fisher 1 2 3,  Arun J Sanyal 4,  Devanand Sarkar 5 2 3
Affiliations

Affiliations

  • 1 Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.
  • 2 VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
  • 3 VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, Virginia.
  • 4 Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.
  • 5 Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia. [email protected].
PMID: 28428278 DOI: 10.1158/0008-5472.CAN-17-0298
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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