微小RNA-128 抑制BMI1 抑制乳癌細胞轉移之研究

癌症一直是人類十大死因前幾位，而乳癌更為全球女性癌症死亡第二位。乳癌細胞的轉移正是造成此疾病高死亡率的主要原因。過去研究發現BMI1 (B-cell-specific Moloney murine leukemia virus insertion site1) 蛋白在乳癌細胞中大量表現會促進上皮-間質轉型 (epithelial-mesenchymal transition,EMT) 進而誘導乳癌細胞的轉移。此外，許多研究指出MicroRNAs 對腫瘤轉移扮演著重要的角色，因此我們推測MicroRNAs 可能藉由調控BMI1 表現，控制腫瘤轉移的能力。本研究的目的是要尋找具有抑制BMI1 表現的MicroRNA，並利用MicroRNA 抑制乳癌轉移。首先，我們利用Targetscan、miRanda 以及 DIANA-microT 3 個生物資訊分析軟體搜尋可能抑制BMI1 的MicroRNA，結果發現MicroRNA-128 具有抑制BMI1 的潛力。從實驗結果中發現BMI1 和 MicroRNA-128 的表現量在不同轉移能力的乳癌細胞株中呈現相反的趨勢。藉由細胞轉染實驗，我們發現，給予MicroRNA-128 會使MDA-MB-231 的BMI1 表現量下降，同時抑制EMT 以及細胞的移行和侵襲能力。相反的，給予 As-miR-128 則會提升M10 細胞株的BMI1 表現，並促進EMT 發生，此證據顯示MicroRNA-128 可調控BMI1 的表現，並抑制EMT 的發生，最終使細胞移行及侵襲能力的下降。綜合實驗中的結果，我們證實了MicroRNA-128 可以藉由抑制BMI1 的表現進而抑制了細胞中EMT 現象的發生導致乳癌細胞轉移能力的下降。

關鍵字

乳癌轉移

並列摘要

Breast cancer is the second highest diagnosed cancer in women. It has the characteristic feature of spread from its original place to other organs. More and more evidences showed that MicroRNAs (miRNAs) play an important role in cell migration. Therefore,we thought that miRNAs and its related genes might are involved in breast cancer cell metastasis. According to the past researches , the overexpression of BMI1 would induce breast cancer metastasis and MicroRNA-128 could suppress BMI1 efficiently. However little is known about that whether MicroRNA-128 would affect the ability of invasion and migration in breast cancer. In order to further conform these results. Here we show that MicroRNA-128 is downregulated in breast cancer cell lines when compare to normal breast cell lines. On the other way, the protein level of BMI1 in breast cancer cancer and normal breast cell lines were negatively correlated to the expression levels of MicroRNA-128 in these cell lines. When we ovexpression of MicroRNA-128 suppressed the level of BMI1 protein in MDA-MB-231,we also found the EMT and cell migration ability would be suppressed. Taken togethers, our study demonstrates that MicroRNA-128 can inhibit cell migration of breast cancer cells through targeting BMI1.