循环microRNAs的外泌形成机制及其对乳腺癌侵袭和转移的影响  

The Active Excretion Mechanism of Circulating microRNAs and Their Effects on Invasion and Metastases of Breast Cancer

作　　者：万晓庆[1,2] 王学健[1] 王艺斐[1,2] 姜雨[1,2] 路中[1,2] 史立宏[1] 丁怡[1] 王丽华[1,2] 

机构地区：[1]潍坊医学院分子肿瘤学实验室,潍坊261053 [2]潍坊医学院附属医院,潍坊261053

出　　处：《生物化学与生物物理进展》2017年第4期269-278,共10页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81472489);山东省科技发展计划(2014GGB14403)资助项目~~

摘　　要：目前乳腺癌的临床诊疗主要依赖影像学和相对较少的预后/预测指标(如雌激素受体、孕激素受体、HER2等).这些生物标志物主要是基于原发肿瘤病灶的生物学检测,可用于转移或复发的检测指标很少,尤其是在切除肿瘤原发灶后,复发监测很困难.循环cell-free microRNAs(circulating cf-miRNAs,或简称circulating miRNAs)的发现为改变现有乳腺癌临床诊疗模式提供了可能.Cell-free miRNA通过外泌体、微囊或转运蛋白的主动外泌机制,可能在循环miRNA的形成中起着重要作用.Cell-free miRNA特别是circulating miRNA不仅自身可以作为信号分子影响肿瘤细胞和组织微环境,而且还可以与其他信号通路发生交互通讯来调控肿瘤部位新生血管的形成和肿瘤细胞表型的上皮-间质转换,影响乳腺癌的侵袭和转移.本文综述了循环miRNA的特征与分泌机制,特别是乳腺癌相关的循环miRNA参与作为一种液体活检生物标志物在乳腺癌诊断、预后评价和疗效评估的临床意义.The current clinical diagnosis and treatment of breast cancer relies on imaging and several prognostic/predictive biomarkers such as estrogen receptor, progesterone receptor, and HER2. Since these biomarkers are mainly derived from primary tumor tissues, they are limited to be applied for monitoring metastases and recurrence, especially after the removal of primary lesion. The discovery of circulating cell-free microRNAs（circulating cf-miRNAs, also called circulating miRNAs） may offer the opportunity to improve the clinical cure patterns of breast cancer. The mechanism of active excretion of cell-free miRNAs via exosomes, microvesicles and other transporters may play an important role in the formation of circulating miRNAs. Cell-free miRNAs,especially circulating miRNAs, not only act as endogenous signaling molecules to influence behaviors of tumor cells and their microenvironment, but also regulate invasion and metastases of breast cancer cells by communication with other signaling pathways to regulate tumor angiogenesis and epithelial-to-mesenchymal phenotypic transition of cancer cells. This article reviews the molecular mechanism of active excretion of circulating miRNAs and the clinical potential of breast cancer-related circulating miRNAs as liquid biopsy biomarkers in diagnosis, prognosis and response evaluation of breast cancer.

关 键 词：MICRORNA CELL-FREE MICRORNAS 循环MICRORNA 主动外泌 乳腺癌 转移 

分 类 号：Q55[生物学—生物化学]