SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297-Mediated S-Adenosylmethionine-Dependent Positive Feedback Loops

Cancer Research
Tao GuoQuanyan Liu

Abstract

Aberrant genome-wide hypomethylation and long noncoding RNA (lncRNA) dysregulation are associated with hepatocarcinogenesis. However, whether a relationship between the two exists remains largely unknown. S-adenosylmethionine (SAMe)-dependent methylation is a critical factor in genomic methylation. We previously found that SNHG6 lncRNA acted as an oncogene in hepatocarcinogenesis and could be considered a potential prognostic indicator for hepatocellular carcinoma (HCC). Here we verify that SNHG6 leads to genome-wide hypomethylation in hepatoma cells and that SNHG6 negatively correlates with the steady-state SAMe concentration in vivo and in vitro SNHG6 suppressed MAT1A protein expression by activating the miR-1297/FUS pathway to regulate nucleocytoplasmic shuttling of MAT1A mRNA. In addition, SNHG6 promoted expression of MAT2A by suppressing direct binding of miR-1297 to the MAT2A 3'UTR. SNHG6 regulated steady-state SAMe levels via coupling of two miR-1297-mediated SAMe-dependent positive feedback loops. Interestingly, the effect of SNHG6 on genome-wide methylation was inhibited by exogenous SAMe within a certain concentration range. These results suggest that single lncRNA dysregulation can lead to aberrant genome-wide hypome...Continue Reading

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Citations

Jan 11, 2019·Journal of Hematology & Oncology·Mu XuShukui Wang
Mar 27, 2019·Molecular Biology Reports·Youji YanKaiyu Qian
Jun 11, 2020·Cancer Cell International·Hui-Shan WangLin Miao
Aug 2, 2020·Seminars in Cancer Biology·Ammad Ahmad FarooqiMassimo Mallardo
Mar 1, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Shouquan DongQiu Zhao
Apr 15, 2021·Cancer Cell International·Yuhong GuoZhiping Zhang
Apr 17, 2021·Frontiers in Molecular Biosciences·Yu CaoChunjing Li
Jul 10, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shahin Alizadeh-FanalouForogh Mohammadi
Aug 10, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaoting LinFeng Ye
Oct 15, 2021·Journal of Cellular Physiology·Chenming ZhongShiwei Duan

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