Activation of lipogenesis by hematopoietic‐ and neurologic‐expressed sequence1 stimulates hepatocellular carcinoma cell proliferation and metastasis

Abstract

Hepatocellular carcinoma (HCC) is the second most common cause of cancer‐related mortality worldwide and its five‐year survival rate is less than 12%. Since it has been reported that hematopoietic‐ and neurologic‐expressed sequence1 (HN1) gene is upregulated in various cancers, its functional significance in HCC remains unclear. Thus, we investigated the biological role of HN1 in HCC using HepG2 and SNU449 cells. HN1 was significantly overexpressed in HCC tumors compared to normal liver tissues. Silencing of HN1 significantly diminished the viability of HCC cells whereas overexpression of HN1 stimulated the viability of HCC cells. Silencing of HN1 increased apoptotic proteins and increased the number and size of colonies. In addition, silencing of HN1 inhibited the invasion and metastasis of HCC cells whereas overexpression of HN1 promoted the invasion and metastasis of HCC cells. In gene expression profiling, we identified 130 upregulated genes and 379 downregulated genes after HN1 silencing in HCC cells. Putative gene networks revealed suppressed expression of proteins associated with lipogenic signaling pathway. Silencing of HN1 significantly inhibited the expression levels of SREBP1 and SREBP2 of HCC cells whereas overexpression of HN1 increased the expression levels of SREBP1 and SREBP2 of HCC cells. In addition, silencing of SREBP1 also diminished the expression levels of HN1 and suppressed the survival and metastasis of HCC cells. In cholesterol assay and triglyceride assay, silencing of HN1 inhibited the lipid formation of HCC cells whereas overexpression of HN1 promoted the lipid formation of HCC cells. Taken together, HN1 encourages the proliferation, invasion and metastasis of HCC cells in part through the activation of SREBP signaling pathway. Therefore, our results suggest that targeting HN1 may constitute a potential therapeutic strategy for HCC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.