课题组研究表明Clcf1/Jak2/stat3是绝经后骨质疏松症（PMOP）肾阴虚证的重要信号通路，且Lnc uc.431+及靶基因Clcf1表达下调，因此提出“假说”：Lnc uc.431+下调导致Clcf1/Jak2/Stat3通路失调是PMOP肾阴虚证的分子机制之一。本研究拟①临床进一步验证Lnc RNA与PMOP肾阴虚证的相关性；RIP验证与Clcf1的相互作用；②过表达及敲低THP1细胞株Lnc uc.431+，分析对Clcf1/Jak2/Stat3信号通路及细胞增殖、周期的影响；③CRISPR/cas9技术敲除小鼠Lnc uc.431+，观察对小鼠外周血Clcf1/Jak2/Stat3的影响；④RIP实验验证调控Lnc uc.431+的转录因子NFATC2；RNA-蛋白相互作用组学实验鉴定与Lnc uc.431+互作蛋白；从长链非编码RNA水平探讨PMOP肾阴虚证的分子机制。

Our previous studies showed that the Clcf1/Jak2/stat3 signal pathway plays important roles in kidney-yin deficiency syndrome of postmenopausal osteoporosis (PMOP). Lnc uc.431+ and its target gene Clcf1 were down-regulated in kidney-yin deficiency syndrome of PMOP. We put forward the hypothesis that the imbalance of Clcf1/Jak2/stat3 signaling pathway mediated by down regulation of Lnc uc.431+ is one of the molecular mechanism of kidney-yin deficiency syndrome inPMOP . Firstly, This study intends to veryfy the correlation between Lnc RNA and kidney-yin deficiency syndrome of PMOP. RIP experiment was used to verify the interaction between Lnc uc.431+ and Clcf1; Secondly, Thp1 cell lines with over expression or knockdown of Lnc uc.431+ were screened to analyze the effects on the Clcf1/Jak2/Stat3 signaling pathway , also cell proliferation and cell cycle; Thirdly, RIP experiment was used to verify the upstream transcription factor NFATC2 regulation on Lnc uc.431+; Lnc uc.431+-protein interaction experiments were performed to identify the other interacting proteins of Lnc uc.431+. Fourly, CRISPR/cas9 technique was used to knockout Lnc uc.431+ in mice, observe the effect of deletionf of Lnc uc.431+ on Clcf1/Jak2/Stat3 signal pathway in peripheral blood. We investigate the molecular mechanism of kidney-yin deficiency syndrome of PMOP from long chain non-coding RNA level.