子宮內膜異位症是一種常見的婦科疾病，其特徵為子宮內膜異位的組織透過經血逆流至子宮腔外生長。育齡年齡的婦女中約有百分之10到15患有此疾病，其中被隨著嚴重的骨盆疼痛的症狀，嚴重的話甚至會導致不孕。不幸的是子宮內膜異位症的病因尚不清楚，並且臨床上並沒有有效治療子宮內膜異位症的方法。微小核醣核酸（miRNA）為一種包含了21到23個非編碼核苷酸的單股序列，透過與其下游基因信使核糖核酸（mRNA）的3’非轉譯區（3’UTR）作用，進而去調控下游基因的穩定度和轉譯效率。越來越多的證據證明了微小核醣核酸可能參與在疾病的發病機制當中，其中包括子宮內膜異位症。為了去探討微小核醣核酸在子宮內膜異位症中的病理機制，我們使用基因表達綜合數據庫（GEO）分析了子宮內膜異位症的微陣列數據（microarray datasets）。透過分析三個線上數據庫（miRTarBase，miRWalk和TargetScan）預測微小核醣核酸21的下游靶基因，並和兩個基因表達綜合數據庫數據（GSE11691和GSE58178）進行交叉比對以推斷潛在的致病基因。經過分析，我們發現39個基因可能會受到微小核醣核酸21的調控，同時參與在子宮內膜異位症的病程發展當中。為了確認預測結果，我們進一步在StarBase上搜尋我們感興趣的三個基因。結果證明在三個基因當中皆有微小核醣核酸21能夠標靶結合的3端非轉譯區。接下來，我們想去探討在子宮內膜異位症組織和細胞中三個有潛力的基因的表達量。結果顯示，這些潛力基因在子宮內膜異位組織中表現量較低，但在異位基質細胞當中只有細胞分裂週期蛋白25A（CDC25A）有顯著降低。因此，我們使用免疫組織化學染色（IHC）進一步對子宮內膜異位症臨床組織進行了細胞分裂週期蛋白25A的染色。結果顯示，在病變的異位基質細胞部分中，細胞分裂週期蛋白25A的表達量不論是在分泌期或增生期皆較原位基質細胞來的低。在缺氧處理下或轉染微小核醣核酸21的類似物到原位基質細胞後，細胞分裂週期蛋白25A的蛋白表達量顯著降低了。綜合上述資訊，微小核醣核酸21抑制了細胞分裂週期蛋白25A的表達量，而此機制可能參與在子宮內膜異位症的病程發展當中。

Endometriosis is a common gynecological disease that is characterized as the presence of endometriotic lesions growing outside of the uterine cavity. About 10-15% of women in reproductive age suffer from this disease with severe pelvic pain and even infertility. Unfortunately, the etiology of endometriosis remains unknown and there is no effective treatment to cure this disease. MicroRNAs (miRNAs) are single-stranded non-coding RNA molecules containing 21-23 nucleotides that regulate the stability or translational efficiency of targeted mRNAs by interacting with the 3’ untranslated region (3’UTR). A growing body of evidence indicates that miRNAs may involve in pathogenesis of diseases, including endometriosis. To characterize the pathological effects of miRNAs in endometriosis, we analyzed the endometriosis microarray datasets by using Gene Expression Omnibus (GEO). First, we employed three online available servers (miRTarBase, miRWalk and TargetScan) to predict the downstream target genes of miR21. We further retrieved the genes downregulated in endometriotic tissue from GEO datasets (GSE11691 and GSE58178) and cross-referenced the miR21 target genes with these endometriotic down-regulated genes to infer potential pathogenic genes. After analysis, we found 39 genes may involve in endometriosis and regulated by miR21. To confirm the predicted result, we further check three genes we are interested on StarBase. The result showed miR21 is able to target on those genes’ 3’UTRs. We next determined the expression level of three candidate genes in endometriotic tissues and cells. The result showed these candidates genes are downregulated in endometriotic tissues, but only CDC25A is significant decreased in ectopic stromal cells compared to eutopic stromal cells. Therefore, we further stained endometriotic tissues for CDC25A by using immunohistochemistry. The result revealed that CDC25A level is lower in both secretory phase and proliferating phase compared to eutopic lesions. Treatment of eutopic endometrial stromal cells with hypoxia or overexpression of miR21 mimics decreased level of CDC25A. Taken all together, the results suggest that CDC25A is downregulated by miR21 in endometriosis and may contribute to the pathological process of endometriosis.

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