miR-184靶向lncRNA UCA1介导FMRP/HCN1表达在伴海马硬化性内侧颞叶癫痫的发病机制研究

超极化激活环核苷酸门控通道HCN基因与海马硬化性内侧颞叶癫痫综合征（Mesial temporal lobe epilepsy with hippocampus sclrosis，MTLE-HS）密切相关，但其下调机制仍不清楚。作为一种获得性癫痫，表观遗传在HCN基因表达下调中起决定作用，本课题组前期表明MTLE-HS大鼠模型和患者手术标本中的HCN1和HCN2下调与DNA甲基化及组蛋白乙酰化相关，本研究将进一步从表观遗传学的角度，深入探讨非编码RNA与HCN1下调的关系，证实lncRNA UCA1和miR-184在MTLE-HS发病中的重要作用，揭示miR-184靶向长链非编码RNA尿路上皮癌胚抗1（UCA1）调控FMRP介导HCN1下调的分子机制。同时利用iplex探讨非编码蛋白基因UCA1基因和miR-184基因多肽性与MTLE-HS遗传易感性之间的关系。

It plays an important role of Hyperpolarization-activated cyclic nucleotide-gated channel (HCN) in Mesial temporal lobe epilepsy and hippocampal sclerosis(MTLE-HS). Several studies in human brain specimen and animal models of MTLE-HS have reported HCN expression declined while the mechanism is unclear. As a kind of acquired epilepsy, epigenetic plays a decisive role in the HCN gene expression decline. Early results showed that HCN1 hypermethylation and histone acetylation in MTLE-HS rat model and patients' brain specimen which they concurrent regulated the HCN expression declined after regulation. This study will further explore the relationship between non-coding RNA and HCN1 down-regulation. In addition, we will confirm the key role of lncRNA UCA1 and mir-184 in the pathogenesis of MTEL-HS, and reveal the molecular mechanism by which miR-184 regulates UCA1 to affect the expression of FMRP and HCN1 and thus participate in the pathogenesis of MTEL-HS. We also will use the iPLEX technology to explore the relationship between the non-coding protein genes UCA1 and miR-184 gene polymorphisms and MTLE-HS genetic susceptibility.