探討miR-503抑制乳癌細胞侵襲轉移之機制

血管內皮生長因子A(vascular endothelial growth factor A ,VEGFA)，在正常人體組織中由促進血管內皮生長因子與抗血管內皮生長因子互相抗衡，使人體血管可以正常分化和生成。然而在腫瘤組織需要養分，就會促使促進血管內皮生長因子的表現，而MMP-9、CXCR4、CXCR7都會活化VEGFA，造成血管開始大量新生，提供腫瘤組織養分。而微小核糖核酸 (microRNA,miRNA)會參與腫瘤細胞的遷移、侵襲和生長。首先藉由Targetscan網站預測miR-503可與VEGFA三端非編碼區( 3’-UTR)結合降低VEGFA的表現，再將乳癌細胞MDA - MB -231穩定表達miR-503基因，再進行細胞存活率分析(MTT assay)，發現隨著時間增加，miR-503有效降低細胞增生速率，再利用Boyden chamber進行細胞遷移與侵襲的試驗，其結果均會受到miR-503的抑制而降低。之後再抑制miR-503與沉默VEGFA，其結果會造成細胞遷移與侵襲能力增加與降低。而再將VEGFA重新設計接在pcDNA3上，使miR-503無法結合到VEGFA 3’-UTR而使MDA-MB-231細胞的遷移與侵襲能力增加。因此，miR-503可以抑制VEGFA的表現，進而抑制乳癌細胞MDA-MB-231的轉移與侵襲能力。

Vascular endothelial growth factor A (VEGFA)in normal tissue can promoting the anti-vascular endothelial growth factor and vascular endothelial growth factor to balancing,so that can be normal differentiation and blood vessel formation. However, in the tumor tissue nutrient needs,and MMP-9, CXCR4, CXCR7 will activate VEGFA, resulting in large number of new blood vessels begin to provide tumor tissue nutrient. The microRNA (miRNA) will be involved in tumor cell migration, invasion and growth. First, we used Targetscan website predict miR-503 can be combined with VEGFA 3’-untranslated region (3''-UTR) reduced VEGFA expression. Then breast cancer cells stably expressing miR-503 gene, and then analyzed for cell viability (MTT assay) ,miR-503 reduces the rate of cell proliferation when time increases. We used Boyden chamber for cell migration and invasion assay, and miR-503 inhibit the cell migration and invasion. Inhibition of miR-503 and knockdown VEGFA, the cell migration and invasion will increased and decreased. And construct the VEGFA to pcDNA3, so miR-503 can not be combined to VEGFA 3''-UTR then cell migration and invasion are increased. Therefore, miR-503 can inhibit VEGFA expression and inhibiting breast cancer MDA-MB-231 cell migration and invasion.