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SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297-Mediated S-Adenosylmethionine-Dependent Positive Feedback Loops
Guo, Tao1; Wang, Hongling2,3; Liu, Pengpeng1; Xiao, Yushao1; Wu, Ping1; Wang, Yitao1; Chen, Baiyang1; Zhao, Qiu2,3; Liu, Zhisu1; Liu, Quanyan1
2018-07-15
Source PublicationCANCER RESEARCH
ISSN0008-5472
Volume78Issue:14Pages:3849-3864
AbstractAberrant 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 hypomethylation by inhibiting SAMe production in HCC and that exogenous SAMe may be beneficial in the treatment of HCC.
DOI10.1158/0008-5472.CAN-17-3833
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000439199100010
PublisherAMER ASSOC CANCER RESEARCH
The Source to ArticleWOS
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Wuhan Univ, Zhongnan Hosp, Digest Dis Res Ctr, Dept Gen Surg, Wuhan, Hubei, Peoples R China;
2.Wuhan Univ, Zhongnan Hosp, Hubei Clin Ctr, Dept Gastroenterol, Wuhan, Hubei, Peoples R China;
3.Wuhan Univ, Zhongnan Hosp, Key Lab Intestinal & Colorectal Dis, Wuhan, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Guo, Tao,Wang, Hongling,Liu, Pengpeng,et al. SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297-Mediated S-Adenosylmethionine-Dependent Positive Feedback Loops[J]. CANCER RESEARCH,2018,78(14):3849-3864.
APA Guo, Tao.,Wang, Hongling.,Liu, Pengpeng.,Xiao, Yushao.,Wu, Ping.,...&Liu, Quanyan.(2018).SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297-Mediated S-Adenosylmethionine-Dependent Positive Feedback Loops.CANCER RESEARCH,78(14),3849-3864.
MLA Guo, Tao,et al."SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297-Mediated S-Adenosylmethionine-Dependent Positive Feedback Loops".CANCER RESEARCH 78.14(2018):3849-3864.
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