American Association for Cancer Research
00085472can173833-sup-193841_2_supp_4751586_p8k9g9.pdf (10.75 MB)

Figure S1-17, Table S1 and S2 from SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297–Mediated S-Adenosylmethionine–Dependent Positive Feedback Loops

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journal contribution
posted on 2023-03-31, 02:06 authored by Tao Guo, Hongling Wang, Pengpeng Liu, Yushao Xiao, Ping Wu, Yitao Wang, Baiyang Chen, Qiu Zhao, Zhisu Liu, Quanyan Liu

We investigated the change of Genome-wide methylation patterns, DNA methylation patterns, miR-1297 expression after SNHG6 knockdown or overexpression in hepatoma cells. q-PCR was performed to simultaneously detect MAT1A mRNA in the nucleus and cytoplasm after FUS overexpression in Huh7 and Hep3B cells. RIP with q-PCR analysis was utilized to verify the direct interaction between the FUS protein and MAT1A mRNA. RNA FISH was used to study the subcellular localization and visual molecular abundance of SNHG6, miR-1297, FUS mRNA and MAT2A mRNA in Huh7 and Hep3B cells.We also identified that miR-1297 inhibits FUS expression by binding to its 3'UTR.


National Natural Science Foundation of China



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 hypomethylation by inhibiting SAMe production in HCC and that exogenous SAMe may be beneficial in the treatment of HCC.Significance: These findings explore the role of SNHG6 lncRNA in suppressing production of the universal methyl donor SAMe and its impact on global DNA methylation levels in liver cancer and highlight the potential benefit of SAMe for the treatment of liver cancer. Cancer Res; 78(14); 3849–64. ©2018 AACR.

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