| First Author | Lu X | Year | 2014 |
| Journal | Oncol Rep | Volume | 32 |
| Issue | 6 | Pages | 2696-702 |
| PubMed ID | 25333455 | Mgi Jnum | J:281138 |
| Mgi Id | MGI:6367432 | Doi | 10.3892/or.2014.3527 |
| Citation | Lu X, et al. (2014) Knockout of the HCC suppressor gene Lass2 downregulates the expression level of miR-694. Oncol Rep 32(6):2696-702 |
| abstractText | 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 onemonth 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 alpha-induced protein 3 (Tnfaip3) was upregulated, as confirmed by qPCR. The expression of NF-kappaB 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. |
