miR-363新功能：调控子宫内膜间质细胞侵袭力的分子机制研究

Endometriosis is a benign disease, but have the invasion and metastasis characteristics similar to malignant tumor. Clinically, the recurrence rate is high, it has become one difficult problem of gynecological clinical treatment. Via microRNA microarray technique, we demonstrated that miR-363 was significantly down-regulated in endometriosis tissues(especially in the ectopic tissues). Previous study showed that up-regulated expression of miR-363 in ESC could inhibit the invasion ability of ESC Bio-informatic analysis and experiment data indicated that ITGA5 could be a candidate target gene of miR-363, and over-expression of miR-363 could negative regulate the expression of ITGA5. It’s reported that, ITGA5 was closely related to the ESC invasion, indicated that miR-363 may regulate ESC invasive ability through ITGA5.This study will confirm the expression pattern of miR-363, using over-expression and knock down strategies in AA-CELL-24 cells, clarifying the role of miR-363 in the ESC invasion progression by analyzing the cell behavior and molecular characteristics, subsequently clarify the underlying mechanism between miR-363 and ITGA5. There was no report about the function and mechanism of miR-363 in regulating the ESC invasion progression. This study may provide a new target for the gene targeted therapeutics of endometriosis.

子宫内膜异位症具有类似恶性肿瘤侵袭转移的临床特征，复发率高，是妇科临床治疗的重大难题。miR-363是我们采用miRNA芯片筛选出的、在内异症内膜组织（尤其在异位内膜）中显著低表达的差异miRNA。前期发现，在子宫内膜间质细胞（ESC）系中过表达miR-363可抑制ESC侵袭力；生物信息学分析及预实验结果显示ITGA5为miR-363可能的靶标；过表达miR-363可显著降低ESC中ITGA5的表达；而文献报道ITGA5与ESC侵袭力密切相关，提示miR-363可能通过ITGA5调控ESC的侵袭力。研究拟阐明miR-363在内膜组织中的表达规律；采用过表达与沉默策略，明确miR-363对ESC侵袭力的影响；并以ITGA5为机制线索，揭示miR-363调控ESC侵袭力的分子机制。有关miR-363影响子宫内膜间质细胞侵袭力的作用及机制均未见报道，本研究可能为内异症的靶向治疗提供新的靶点。

子宫内膜异位症临床特征表现为：痛经、性交痛、不孕不育，复发率高，是生育年龄妇女最常见、对女性身体和心理均带来严重创伤的妇科疾病。虽然从组织学层面鉴定内异症属良性疾病，但内异症患者的子宫内膜组织却具有类似恶性肿瘤侵袭转移的能力，易种植于卵巢、腹膜、肠管等靶向器官，引起靶向器官的病变，严重降低患者的生活质量。目前临床上广泛使用手术加激素类药物治疗内异症，在一定程度上减轻了患者的症状，但并不能彻底清除异位内膜组织，有效遏制残余内膜组织继续向外周组织的侵袭转移，最终导致患者复发。子宫内膜组织向外周组织的侵袭，是内异症的重要临床特征，也是临床治疗内异症的瓶颈。因此，探讨子宫内膜组织向外周组织的侵袭转移机制无疑对指导内异症的临床治疗具有重要的研究价值。.miR-363是我们采用miRNA芯片筛选出的、在内异症内膜组织（尤其在异位内膜）中显著低表达的差异miRNA。研究发现，子宫内膜间质细胞（ESC）系中过表达miR-363可抑制ESC侵袭力；生物信息学分析结果显示ITGA5为miR-363可能的靶标；萤光素酶实验再次验证了ITGA5为miR-363的靶标；过表达miR-363可显著降低ESC中ITGA5的表达，从而调控ESC的侵袭力；通过挽救试验，再次验证miR-363通过调控ITGA5的表达，从而调控ESC的侵袭力。.研究阐明了miR-363在内膜组织中的表达规律；采用过表达与沉默策略，明确miR-363对ESC侵袭力的影响；并以ITGA5为机制线索，揭示了miR-363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。