miR-27a在乳腺癌耐药中的相关研究进展

Research Advances in Role of miR-27a in Drug Resistance of Breast Cancer

乳腺癌耐药一直是临床及科研工作的难题,但迄今为止耐药机制尚不明确。微RNA(miRNA/miR)参与调节转录后基因的表达,其中miR-27a作为致癌基因在乳腺癌中的表达上调,与乳腺癌耐药紧密相关。miR-27a具有调控药泵外排、激活凋亡抵抗、影响DNA修复损伤以及介导药物失活等多种生物学功能,通过作用于不同的下游靶点,如P-糖蛋白、BAK、第2个线粒体源胱天酶激活剂/低等电点IAP直接结合蛋白等,促进细胞增殖,抑制细胞凋亡,激活下游通路磷脂酶C/Raf/促分裂原活化的蛋白激酶途径、腺瘤性结肠息肉/β联蛋白等,最终导致阿霉素、5-氟尿嘧啶、他莫昔芬等耐药。干扰miR-27a的表达能够逆转乳腺癌化疗耐药,但miR-27a作用机制复杂,其具体作用机制有待进一步阐明。

Drug resistance in breast cancer has been a problem in the clinical and research work,but the mechanism is still unclear.MicroRNA(miRNA/miR)are involved in the regulation of post-transcriptional gene.As a member of miRNAs,miR-27a is up-regulated in breast cancer,and is closely associated with the drug resistance of breast cancer.In the treatment of breast cancer,miR-27a has various biological functions,such as regulating drug pump proteins,activating apoptosis resistance,affecting DNA damage repair and mediating drugs inactivation.miR-27a enhances cell proliferation,reduces cell apoptosis,activates downstream pathways(such as phospholipase C/Raf/mitogen activated protein kinase,adenomatous polyposis coli/β-catenin),and finally results in drug resistance such as doxorubicin,5-fluorouracil and tamoxifen by acting on different downstream targets(such as p-glycoprotein,BAK,the second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI).In addition,interference of miR-27a expression can reversedrug resistance of breast cancer.However,the mechanisms of miR-27a in breast cancer resistance are complicated,needing further elaboration on the specifics.