Nuclear factor I-C disrupts cellular homeostasis between autophagy and apoptosis via miR-200b-Ambra1 in neural tube defects.
Nuclear factor I-C disrupts cellular homeostasis between autophagy and apoptosis via miR-200b-Ambra1 in neural tube defects.
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核因子 I-C 通过 miR-200b-Ambra1 在神经管缺陷中破坏自噬和凋亡之间的细胞稳态
DOI：
10.1038/s41419-021-04473-2
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发表时间：
2021-12-20
影响因子：
9
通讯作者：
Yuan Z
中科院分区：
文献类型：
--
作者：
Huang W;Huang T;Liu Y;Fu J;Wei X;Liu D;Ma W;Gu H;Yuan Z
受损的自噬和过度凋亡破坏细胞内稳态并导致神经管缺陷（NTD），其是由早期胚胎发育期间神经管闭合失败引起的一组致命和致残的出生缺陷。然而，NTD和结果的监管机制仍然难以捉摸。在这里，我们报告的作用，转录因子核因子I-C（NFIC）在维持细胞内稳态NTDs。我们证明了NTD小鼠模型中NFIC水平异常升高可以与miR-200 b启动子相互作用，导致miR-200 b转录的激活，这在NTD形成中起着关键作用，正如我们以前的研究所报道的那样。此外，miR-200 b通过直接靶向自噬相关基因Ambra 1（Autophagy/Beclin 1 regulator 1）抑制自噬并触发细胞凋亡。值得注意的是，miR-200 b抑制剂减轻了NFIC对自噬和细胞凋亡的意想不到的影响。总的来说，这些结果表明，NFIC-miR-200 b-Ambra 1轴，它整合了转录和表观基因组调节的miRNA和自噬调节因子，在神经管关闭过程中破坏了细胞的稳态，并可能为NTD发病机制提供新的见解。
Impaired autophagy and excessive apoptosis disrupt cellular homeostasis and contribute to neural tube defects (NTDs), which are a group of fatal and disabling birth defects caused by the failure of neural tube closure during early embryonic development. However, the regulatory mechanisms underlying NTDs and outcomes remain elusive. Here, we report the role of the transcription factor nuclear factor I-C (NFIC) in maintaining cellular homeostasis in NTDs. We demonstrated that abnormally elevated levels of NFIC in a mouse model of NTDs can interact with the miR-200b promoter, leading to the activation of the transcription of miR-200b, which plays a critical role in NTD formation, as reported in our previous study. Furthermore, miR-200b represses autophagy and triggers apoptosis by directly targeting the autophagy-related gene Ambra1 (Autophagy/Beclin1 regulator 1). Notably, miR-200b inhibitors mitigate the unexpected effects of NFIC on autophagy and apoptosis. Collectively, these results indicate that the NFIC-miR-200b-Ambra1 axis, which integrates transcription- and epigenome-regulated miRNAs and an autophagy regulator, disrupts cellular homeostasis during the closure of the neural tube, and may provide new insight into NTD pathogenesis.
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影响因子：
3.8
作者：
Gu, Hui;Yu, Jingwen;Yang, Peixin
通讯作者：
Yang, Peixin
DOI：
10.1038/nrdp.2015.7
发表时间：
2015-04-30
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Copp AJ;Adzick NS;Chitty LS;Fletcher JM;Holmbeck GN;Shaw GM
通讯作者：
Shaw GM
DOI：
10.1016/j.jalz.2016.12.012
发表时间：
2017-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Jun GR;Chung J;Mez J;Barber R;Beecham GW;Bennett DA;Buxbaum JD;Byrd GS;Carrasquillo MM;Crane PK;Cruchaga C;De Jager P;Ertekin-Taner N;Evans D;Fallin MD;Foroud TM;Friedland RP;Goate AM;Graff-Radford NR;Hendrie H;Hall KS;Hamilton-Nelson KL;Inzelberg R;Kamboh MI;Kauwe JSK;Kukull WA;Kunkle BW;Kuwano R;Larson EB;Logue MW;Manly JJ;Martin ER;Montine TJ;Mukherjee S;Naj A;Reiman EM;Reitz C;Sherva R;St George-Hyslop PH;Thornton T;Younkin SG;Vardarajan BN;Wang LS;Wendlund JR;Winslow AR;Alzheimer's Disease Genetics Consortium;Haines J;Mayeux R;Pericak-Vance MA;Schellenberg G;Lunetta KL;Farrer LA
通讯作者：
Farrer LA
影响因子：
4.7
作者：
Chen, Wei;Yi, Jin Kyu;Kang, Mo K.
通讯作者：
Kang, Mo K.
影响因子：
64.8
作者：
Fimia, Gian Maria;Stoykova, Anastassia;Cecconi, Francesco
通讯作者：
Cecconi, Francesco