LncRNA TC02004715.hg.1调控TRPV2在子宫内膜异位症发生发展的作用及机制

Endometriosis (Endometriosis, EM) is difficult to cure, but easy to recur, which affects the health of women. However, the key regulating protein and the exact mechanism remains much unclear. In previous studies, we analyzed the human endometrial tissue by high-throughput Affymetrix HTA2.0 chip and depth analysis, and found that long noncoding RNA -- TC02004715.hg.1 exhibited significant higher expression level in ectopic endometrial tissue than that in eutopic endometrium and normal endometrium tissue. TC02004715.hg.1 further regulated the expression of TRPV2 in ectopic endometrium. TRPV2 was reported to contribute to the malignant cell migration and pain regulation. But it is unclear whether it is involved in EM development. To further clarify the regulation and mechanism of LncRNATC02004715.hg.1 on EM development via TRPV2, we plan to establish TC02004715.hg.1 siRNA Knockdown ectopic endometrial cell, Knockdown mice, and conditional knockout mice model to analyze the cellular behaviors, such as migration, invasion, proliferation, and apoptosis. Our original research will sheds light on the understanding of the development of EM and provide valuable theoretical basis for clinical intervention of EM. Our study contributes to improving female health, lowering related health-care costs, and has both scientific and potential clinical value.

子宫内膜异位症（Endometriosis, EM）难根治、易复发，严重影响妇女健康， 其发病的关键调控蛋白或分子机制尚不明确。本课题组前期通过高通量Affymetrix HTA2.0芯片检测、深度分析和验证发现长链非编码RNA TC02004715.hg.1在EM异位内膜的表达显著高于在位内膜及正常对照内膜组织，且TC02004715.hg.1可调控TRPV2通道蛋白在异位内膜的表达。已知TRPV2参与肿瘤细胞迁移和痛觉调节，但其与内异症的关联目前尚无报道。本研究拟进一步采用体外细胞siRNA敲减、在体敲减小鼠、条件性基因敲除小鼠模型，通过ChIRP-seq、RNA免疫共沉淀、细胞迁移/侵袭/增殖/凋亡等细胞行为检测，深入研究TC02004715.hg.1通过TRPV2在EM发生发展中的作用、关键调控环节及机制，探索EM发生新理论，为EM临床干预提供新的靶点，改善女性健康。

子宫内膜异位症是指子宫内膜样组织出现在子宫腔以外的部位，常见的部位有卵巢、阴道直肠陷窝、腹膜，罕见的部位包括远隔部位的肺和脑。子宫内膜异位症在育龄期妇女中的发病率约为5-10%，主要引起痛经、不孕、盆腔痛等症状，严重影响女性生活质量。长链非编码RNA（long noncoding RNA, 简称lncRNA）是指长度超过200碱基且不具有蛋白质编码功能的RNA。大量的lncRNA广泛参与多种重要的调控过程，如染色质沉默、基因组印记、染色质修饰、转录激活、转录干预和核转运等。lncRNA不仅在肿瘤、衰老、心血管疾病的发生发展中起着重要作用，它在内异症中的作用也越来越受到关注。本研究通过基因芯片发现lncRNA TC02004715.hg.1在内异症异位内膜组织中明显高于在位内膜组织及非内异症患者正常子宫内膜组织，通过生信预测发现它与瞬时感受器电位离子通道蛋白 V 亚族 2(TRPV2)基因可能存在较强的相互作用。经过qRT-PCR、western blot、CCK-8、transwell、流式细胞术、FISH等一系列分子细胞实验，我们发现lncRNA TC02004715.hg.1即linc01116，在内异症异位组织中高表达，与TRPV2的表达呈正相关，linc01116上调促进TRPV2表达，并促进子宫内膜间质细胞增殖、迁移、侵袭并抑制凋亡，而linc01116下调则抑制TRPV2表达，抑制增殖、迁移、侵袭并促进凋亡，此在体实验结果也揭示了linc01116和TRPV2下调可明显缩小病灶大小，上皮间质转化可能参与了linc01116和TRPV2对间质细胞功能的调控，影响内异症的发生发展。通过对lin01116/TRPV2/EMT机制的研究可以为内异症的治疗提供靶点和新思路