Knockout of the HCC suppressor gene Lass2 downregulates the expression level of miR-694

Lu,Xiaodong; Chen,Yuanyuan; Zeng,Tiantian; Chen,Lufang; Shao,Qixiang; Qin,Wenxin

doi:10.3892/or.2014.3527

Knockout of the HCC suppressor gene Lass2 downregulates the expression level of miR-694

Authors:
- Xiaodong Lu
- Yuanyuan Chen
- Tiantian Zeng
- Lufang Chen
- Qixiang Shao
- Wenxin Qin
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Affiliations: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai 200032, P.R. China, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
Published online on: October 3, 2014 https://doi.org/10.3892/or.2014.3527
Pages: 2696-2702

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Abstract

Homo sapiens longevity assurance homolog 2 of yeast LAG (Lass2) catalyzes the synthesis of long-chain ceramide which is an essential element of membranous structures. Deletion of Lass2 is associated with a high risk of spontaneous or DEN-induced hepatocellular carcinoma (HCC), yet the mechanism remains unclear. In the present study, we found extensive vesicles in hepatocytes of one-month-old Lass2-knockout (KO) mice. Hepatic biochemical indices were increased and expression of albumin was attenuated in the one‑month Lass2-KO liver. The results indicate that the injuries of the hepatocytes in young Lass2-KO mice, based on the results of Gene Ontology analysis of mRNA microarray of Lass2-KO liver vs. wild-type liver showed ‘wounding response’ was the mostly possible altered pathway in the Lass2-KO mice. miR-mRNA integrated analysis revealed that miR-694 was downregulated while its target gene tumor necrosis factor α-induced protein 3 (Tnfaip3) was upregulated, as confirmed by qPCR. The expression of NF-κB which is negatively controlled by Tnfaip3 was detected by qPCR and was found to be downregulated. Herein, we first report that Lass2 deficiency caused the downregulation of miR-694 and the upregulation of its target gene Tnfaip3 in vivo in mice, which may be related to a high risk of occurrence of HCC.

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