一碳代谢调节阿尔茨海默病中的miR-29a- DNA甲基化串扰。
One-carbon metabolism modulates miR-29a-DNA methylation crosstalk in Alzheimer's disease.
作者信息
Raia Tiziana, Cavallaro Rosaria A, Borges Luiza Diniz Ferreira, Cinti Stefano, Bizzarri Mariano, Ferrer Isidre, Lucarelli Marco, Fuso Andrea
机构信息
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Department of Surgery, Sapienza University of Rome, Rome, Italy.
出版信息
Alzheimers Dement. 2025 Sep;21(9):e70703. doi: 10.1002/alz.70703.
INTRODUCTION
Alzheimer's disease (AD)'s multifactorial nature stresses the role of epigenetics in affecting different pathological pathways. We demonstrated that one-carbon metabolism epigenetically impacts AD-like phenotype. Here, we investigated the crosstalk between methylation and microRNAs in AD.
METHODS
We altered one-carbon metabolism to induce hypo- and hyper-methylation, in SK-N-BE neuroblastoma cells and TgCRND8 mice. miRNAs were profiled through a polymerase chain reaction array, then we focused on miR-29a expression and methylation of its genomic locus. Finally, we assessed miR-29a expression and methylation in the brain of AD subjects.
RESULTS
MiR-29a was repressed in hypomethylating and expressed in hypermethylating conditions. The expression of miR-29a and of its target, BACE1, was inversely correlated.
DISCUSSION
We demonstrated for the first time that miR-29a is modulated by one-carbon metabolism through DNA methylation, disclosing the molecular mechanisms regulating BACE1 expression in AD. These data confirm miR-29a's protective role in AD and support miR-29a as a potential biomarker for AD.
引言
阿尔茨海默病（AD）的多因素性质强调了表观遗传学在影响不同病理途径中的作用。我们证明了一碳代谢在表观遗传上影响AD样表型。在此，我们研究了AD中甲基化与微小RNA之间的相互作用。
方法
我们在SK-N-BE神经母细胞瘤细胞和TgCRND8小鼠中改变一碳代谢以诱导低甲基化和高甲基化。通过聚合酶链反应阵列分析微小RNA，然后我们聚焦于miR-29a的表达及其基因组位点的甲基化。最后，我们评估了AD患者大脑中miR-29a的表达和甲基化情况。
结果
miR-29a在低甲基化条件下受到抑制，在高甲基化条件下表达。miR-29a及其靶标BACE1的表达呈负相关。
讨论
我们首次证明miR-29a通过DNA甲基化受一碳代谢调节，揭示了AD中调节BACE1表达的分子机制。这些数据证实了miR-29a在AD中的保护作用，并支持miR-29a作为AD的潜在生物标志物。
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