MiR-22, regulated by MeCP2, suppresses gastric cancer cell proliferation by inducing a deficiency in endogenous S-adenosylmethionine.
MiR-22, regulated by MeCP2, suppresses gastric cancer cell proliferation by inducing a deficiency in endogenous S-adenosylmethionine.
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MiR-22 受 MeCP2 调节，通过诱导内源性 S-腺苷甲硫氨酸缺乏来抑制胃癌细胞增殖
DOI：
10.1038/s41389-020-00281-z
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发表时间：
2020-11-10
期刊：
影响因子：
6.2
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Tong D;Zhang J;Wang X;Li Q;Liu L;Lu A;Guo B;Yang J;Ni L;Qin H;Zhao L;Huang C
本研究调查了甲基 CpG 结合蛋白 2 (MeCP2) 对 miRNA 转录的影响。我们的 miRNA 芯片测定和 ChIP-seq 的结果表明，MeCP2 通过结合多种 miRNA 的上游元件（不仅包括启动子，还包括远端增强子）来抑制其表达。在受影响的 miRNA 中，miR-22 通过靶向 MeCP2、MTHFD2 和 MTHFR 显着抑制胃癌 (GC) 细胞增殖、阻止 G1-S 细胞周期转变并诱导细胞凋亡。了解GC代谢特征是开发针对GC代谢途径的新疗法的关键。我们的研究表明GC组织的代谢谱发生了改变。 SAM（S-腺苷甲硫氨酸）是组蛋白和 DNA 甲基化的通用甲基供体，特别参与癌细胞的表观遗传维持，其含量有所增加。叶酸循环促进 SAM 的产生。叶酸代谢和甲基供体 SAM 生成中的两种关键酶 MTHFD2 和 MTHFR 的敲低可显着抑制 GC 细胞增殖。MiR-22 过表达通过抑制 MTHFD2 和 MTHFR 降低内源 SAM 水平，诱导 P16、PTEN 和 RASSF1A 低甲基化。总之，我们的研究表明miR-22被MeCP2抑制，导致内源性SAM缺乏，最终导致抑癌基因失调。
This study investigated the effect of methyl-CpG-binding protein 2 (MeCP2) on miRNA transcription. Our results of miRNA chip assay and ChIP-seq showed thatMeCP2inhibited the expressions of numerous miRNAs by binding to their upstream elements, including not only the promoter but also the distal enhancer. Among the affected miRNAs,miR-22was identified to remarkably suppress gastric cancer (GC) cell proliferation, arrest G1–S cell cycle transition, and induce cell apoptosis by targetingMeCP2,MTHFD2, andMTHFR. Understanding GC metabolism characteristics is the key to developing novel therapies that target GC metabolic pathways. Our study revealed that the metabolic profiles in GC tissues were altered. SAM (S-adenosylmethionine), a universal methyl donor for histone and DNA methylation, which is specifically involved in the epigenetic maintenance of cancer cells, was found increased. The production of SAM is promoted by the folate cycle. Knockdown ofMTHFD2andMTHFR, two key enzymes in folate metabolism and methyl donor SAM production, significantly suppressed GC cell proliferation.MiR-22overexpression reduced the level of endogenous SAM by suppressingMTHFD2andMTHFR, inducingP16,PTEN, andRASSF1Ahypomethylation. In conclusion, our study suggests thatmiR-22was inhibited by MeCP2, resulting in deficiency of endogenous SAM, and ultimately leading to tumor suppressor dysregulation.
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影响因子：
5.4
作者：
Dong X;Xu M;Ren Z;Gu J;Lu M;Lu Q;Zhong N
通讯作者：
Zhong N
影响因子：
3.7
作者：
Feng Y;Huang W;Wani M;Yu X;Ashraf M
通讯作者：
Ashraf M
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B
DOI：
10.1016/j.niox.2014.03.001
发表时间：
2014-09-15
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Módis K;Coletta C;Asimakopoulou A;Szczesny B;Chao C;Papapetropoulos A;Hellmich MR;Szabo C
通讯作者：
Szabo C
影响因子：
5.4
作者：
Ahmad, Hafiz M.;Muiwo, Pamchui;Bhattacharya, Alok
通讯作者：
Bhattacharya, Alok