lncBC091332与miRNA-182协同调控DRR1在锰致机体认知损害中的作用及其作用机制研究

Long non-coding RNAs (lncRNA) is a new and important class of non-protein coding RNAs which have importantly biologically relevant function. LncRNA has become one of most active research fields in genomics, since it has been associated with lots of serious diseases including neurodegenerative disease. However, whether lncRNA plays a role in neurotoxicity of manganese remains unknown at present. Our preliminary studies indicated that manganese exposure can led to cognitive impairment in exposed workers and rats. By high-throughput screening and verified experiment, treatment of manganese in primary cultured hippocampal neurons results in an up-regulation of lncRNA-BC091332 and down-regulation of miRNA-182, and DRR1 is a potential target in the meanwhile. Therefore, we make hypothesis that lncRNA-BC091332 may play a key role by regulating DRR1 and interacting with miRNA-182 in cognitive impairment by manganese exposure. Our research will test the hypothesis by shRNA, qRT-PCR, Western-Blot, RNA-RIP, etc. in vivo and vitro. It would be the first time to learn the effect of lncRNA and miRNA in manganese neurotoxicity, and it would provide new perspective to the study of manganese neurotoxicity by our research.

长链非编码RNA（lncRNA）是近年来备受瞩目的一类非编码RNA,不仅具有重要的生物学功能，且与多种重大疾病包括神经退行性疾病的发生密切相关，已成为基因组研究的热点，但其在锰的神经毒性中的作用未见报道。我们前期研究表明大鼠和人群锰暴露后认知能力下降，大鼠海马神经元染锰后lncRNA芯片及验证结果表明lncRNA-BC091332下调，miRNA-182上调，生物信息学分析表明DRR1为其潜在靶标。由此提出：lncRNA-BC091332与miRNA-182协同调控DRR1可能在锰致机体认知功能损害中发挥了重要作用。为验证此假设，拟通过shRNA、qRT-PCR、WB、RNA-RIP等实验，从体内外来探讨lncRNA和miRNA在锰致机体认知能力下降中的可能作用及其机制。本项目首次研究lncRNA和miRNA在锰神经毒性中的作用机制，为了解和研究锰的神经毒性提供了全新的视角。

长链非编码RNA（lncRNA）是近年来备受瞩目的一类非编码RNA,不仅具有重要的生物学功能，且与多种重大疾病包括神经退行性疾病的发生密切相关，已成为基因组研究的热点，但其在锰的神经毒性中的作用少见报道。我们前期研究表明大鼠和人群锰暴露后认知能力下降，大鼠海马神经元染锰后lncRNA芯片检测表明锰暴露后神经元中的lncRNA表达谱和mRNA表达谱皆有变化，但lncRNA及其互作分子在锰致神经毒性中的可能作用及其机制还不是很清楚。本研究采用全转录组测序和qRT-PCR确定锰暴露后异常变化的lnc131101，使用siRNA将其敲降后通过CCK8、FCM、EdU等实验验证lnc131101在锰对神经细胞毒害中的作用，再通过RAP、qPCR、生信分析、WB等方法验证lnc131101的互作分子mmu-miR-675-5p及mmu-miR-675-5p的结合mRNA TRAF3，从体内外来验证lnc131101、mmu-miR-675-5p和TRAF3在锰致神经毒性中的作用及其机制。有望通过该研究进一步阐明锰导致机体认知功能下降的作用机制并找到新的锰暴露的早期效应生物标志物。