功能未知的lncRNA: RP11-512N21.3调控子宫内膜间质细胞侵袭能力的作用与机制研究

Endometriosis is a benign disease, but has the invasion and metastasis characteristics similar to malignant tumor. Clinically, as the recurrence rate ishigh, it has become one of the most difficult problem of gynecological clinical treatment. We demonstrated that RP11-512N21.3 was significantly down-regulated in endometriosis tissues(especially in the ectopic tissues) via lncRNA sequencing technique. Previous study showed that the invasion ability of ESC was inhibited because of up-regulated expression of RP11-512N21.3. Bio-informatic analysis and experiment data indicated that DRAM1 might be a candidate target gene of RP11-512N21.3, and over-expression of RP11-512N21.3 could up regulate the expression of DRAM1. It’s reported that, DRAM1 was related to the ESC invasion closely, indicated that RP11-512N21.3 may regulate ESC invasive ability through DRAM1.This study will confirm the expression pattern of RP11-512N21.3, using over-expression and knock down strategies in ESC cells, clarifying the role of RP11-512N21.3 in the ESC invasion progression by analyzing the cell behavior and molecular characteristics, subsequently clarify the underlying mechanism between RP11-512N21.3 and DRAM1. There was still no report about the function and mechanism of RP11-512N21.3 in regulating the ESC invasion progression. This study may provide a new target for the gene targeted therapeutics of endometriosis.

RP11-512N21.3是我们采用lncRNA测序筛选出的、在内异症内膜中显著低表达、功能未知的一条lncRNA。前期发现，在ESC中过表达RP11-512N21.3可抑制ESC侵袭力；生物信息学分析及预实验结果显示DRAM1可能是RP11-512N21.3的靶标；过表达RP11-512N21.3促进DRAM1的表达；文献报道DRAM1与细胞侵袭相关，提示RP11-512N21.3可能通过DRAM1调控ESC的侵袭力。本研究拟：阐明RP11-512N21.3在内膜组织中的表达规律；明确RP11-512N21.3对ESC侵袭力的影响；以DRAM1为线索，揭示RP11-512N21.3调控ESC侵袭力的分子机制；借助CHIP等实验明确RP11-512N21.3调控DRAM1具体的作用方式。有关RP11-512N21.3影响ESC侵袭力的作用及机制尚无报道，本研究可能为治疗内异症提供新的靶点。

子宫内膜异位症是指功能性的子宫内膜腺体或间质发生异位，生长于卵巢、腹膜、肠管等子宫腔以外的组织及器官的一种病变。其虽为良性病变，却具有异位浸润和转移等恶性行为，内异症不仅可以引起不孕，还可以导致不良的妊娠结局，如自然流产和异位妊娠等，严重影响广大育龄妇女的生活质量和家庭和谐。目前临床治疗方案主要为手术加激素类药物，虽然在一定程度上减轻了患者的症状，但并不能彻底清除内膜组织，最终导致患者复发。子宫内膜组织向外周组织的侵袭和异位种植，是内异症发生发展的根本原因，也是临床治疗内异症的瓶颈。因此，深入挖掘影响内膜组织侵袭力的关键调节因素，探讨调控内膜组织的侵袭转移能力的分子机制，进而寻找内异症治疗靶点显得尤为必要。.生物信息学分析显示RP11-512N21.3具有重要的生物学功能，FISH实验结果显示其主要分布于细胞核中，提示其机制可能发生在基因组水平。RP11-512N21.3可抑制子宫内膜间质细胞的增殖、迁移及侵袭能力；DRAM1可能为RP11-512N21.3的靶标；过表达RP11-512N21.3可显著改变DRAM1及侵袭相关基因的表达，从而调控ESC的侵袭力；研究阐明了RP11-512N21.3调控子宫内膜间质细胞增殖、迁移与侵袭能力，揭示了RP11-512N21.3调控ESC侵袭力的分子机制。本研究成果可能为内异症的靶向治疗提供新的靶点。