微RNA-375的抑癌机制

MiR-375 in Cancers Inhibition

微RNA-375(microRNA-375,miR-375)是最早在胰腺组织中发现的微RNA,参与胰岛的形成和发展,具有调节胰岛素分泌的功能.新近研究发现,miR-375在多种肿瘤组织(包括呼吸系统、消化系统、泌尿生殖系统、皮肤和妇科肿瘤组织)中和食管鳞状细胞癌、肝癌和胰腺癌患者外周血中明显表达异常.miR-375可通过调控多个靶基因(如:3-磷酸肌醇依赖性蛋白激酶1、14-3-3ζ、Janus激酶2、p53、丝裂原活化蛋白激酶、Wnt、血管内皮生长因子、胰岛素样生长因子-1受体、星形胶质细胞升高基因-1/异黏蛋白、地塞米松诱导的Ras相关蛋白1和特异蛋白1等相关基因),参与肿瘤的发生和发展过程.提高细胞内miR-375的水平能够抑制肿瘤细胞(如:头颈鳞癌、胃癌、食管鳞癌、黑色素瘤和乳腺癌等肿瘤细胞)的增殖和迁移.因此,具有抑癌活性的miR-375是一种有临床价值的新型肿瘤分子标志物和肿瘤靶向治疗的新靶点.

Identified in pancreatic tissues,mircroRNA-375（miR-375） contributes to the formation and development of islets,as well as the regulation of insulin secretion.Recently,abnormal expression of miR-375 was also found in many tumor tissues,including cancers in respiratory,digestive and genitourinary systems,dermatological or gynecologic tissues.It was also detected in the peripheral blood of patients with esophageal squamous cell carcinoma,hepatocarcinoma and pancreatic cancers.A great variety of genes can be the miR-375 targets,such as 3-phosphoinositide-dependent protein kinase-1（PDK1）,14-3-3ζ,Janus kinase 2（JAK2）,tumor protein p53（TP53）,mitogen-activated protein kinase（MAPK）,wingless-type MMTV integration site family（Wnt） proteins,vascular endothelial growth factor（VEGF）,insulin-like growth factor 1 receptor（IGF-1R）,astrocyte elevated gene-1（AEG-1）/metadherin（MTDH）,dexamethasone-induced Ras-related protein 1（RASD1）,and specificity protein-1（SP1）,etc,all of which involved in carcinogenesis,especially in digestive,head and neck cancers,and gynecologic tumors.As a potential tumor suppressor,elevated miR-375 expression was able to suppress the proliferation and migration in many cancers,therefore,may be regarded as an important tumor biomarker and therapeutic target.