缺氧参与子宫内膜异位症发病过程。我们前期microRNA测序显示，缺氧诱导子宫内膜间质细胞（ESCs）miR-210表达。ESCs敲除miR-210后缺氧处理，细胞周期被阻滞在G2/M期，细胞生长也被抑制，而单独缺氧处理ESCs并未有相应作用。转录组测序显示，miR-210显著下调ESCs细胞周期分裂相关基因的表达。QPCR及Western Blot (WB)验证发现BARD1被miR-210显著抑制，且BARD1 3’-UTR有miR-210结合序列。BARD1可与BRCA1相互结合，增强BRCA1蛋白的稳定性，促进其发挥其细胞周期Checkpoint调控作用。我们将通过PCR、WB、免疫组化及裸鼠内异囊肿模型，验证缺氧诱导的miR-210是否通过靶向BARD1，促进BRCA1蛋白降解，导致细胞周期Checkpoint机制失效，使细胞得以克服缺氧环境继续生长，促进内异症的发展。

Our previous study found hypoxia was involved in the pathogenesis of endometriosis. To better understanding the underling molecular mechanism, small RNA sequencing was performed to compare microRNAs expression difference between hypoxia and normoxia treated cells. Following QPCR confirmation, miR-210 was found elevated by hypoxia. Follow cytometry analysis demonstrated that knockdown miR-210 in endometrial stromal cells (ESCs) followed by hypoxia treatment significant arrested cells at G2/M phase, comparing with control cells treated by hypoxia alone. Transcriptone sequencing indicated that miR-210 inhibited the expression of genes involved in regulation of cell cycle, cell division and microtubule movement, which was highly consist with our cell cycle results. BARD1 was one of the candidate targets of miR-210 that greatly attracted our attention. Validation by QPCR and Western blot, BARD1 was largely repressed by miR-210. Furthermore, miR-210 binding sequence was found in BARD1 3’-UTR by bioinformatics softwares of Targetscan, RNAhybrid and miRanda. BARD1 was well known to bind with BRCA1, increasing it protein stability. By activating cell cycle checkpoint, heterodimer of BRCA1 and BARD1 arrested cell cycle at G2/M phase and initiate DNA damage repair. Herein, we would like to apply PCR, Western blot, immunohistochemistry and endometriotic xenograft nude mouse model to prove our hypothesis: hypoxia induced miR-210 might involve in development of endometriosis by promoting BRCA1 protein degradation via targeting BARD1, wich might probably inactivate cell cycle checkpoint and help endometriotic cells survive in local hypoxia microenvironment