Choi Pui-Wah, Ng Shu-Wing
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Int J Mol Sci. 2017 Jun 6;18(6):1207. doi: 10.3390/ijms18061207.
The majority of studies on microRNA-200 family members (miR-200s) in human cancers are based on the premise that miR-200s maintain epithelial cell integrity by suppressing epithelial-mesenchymal transition (EMT) through direct inhibition of mesenchymal transcription factors zinc finger E-box-binding homeobox 1/2 (ZEB1/ZEB2) and transforming growth factor-β (TGF-β), a potent inducer of EMT. Hence, downregulation of miR-200 in cancer cells promotes EMT and cancer metastasis. Yet, miR-200s are highly expressed in ovarian cancer, and ovarian cancer metastasizes primarily by dissemination within the pelvic cavity. In this review, we will refocus the epithelial property of ovarian cancer cells and the role of miR-200s in safeguarding this property, as well as the diverse roles of miR-200s in inclusion cyst formation, cancer cell growth, collective movement, angiogenesis, exosome-mediated cell communication, and chemoresponse. Taken together, miR-200s play a significant role in the initiation, progression and metastasis of ovarian cancer and may serve as diagnostic biomarkers and a target in therapeutic development.
大多数关于人类癌症中微小RNA-200家族成员(miR-200s)的研究基于这样一个前提,即miR-200s通过直接抑制间充质转录因子锌指E盒结合同源框1/2(ZEB1/ZEB2)和上皮-间质转化(EMT)的强效诱导因子转化生长因子-β(TGF-β)来维持上皮细胞的完整性。因此,癌细胞中miR-200的下调会促进EMT和癌症转移。然而,miR-200s在卵巢癌中高表达,且卵巢癌主要通过在盆腔内播散进行转移。在本综述中,我们将重新关注卵巢癌细胞的上皮特性以及miR-200s在维护这一特性中的作用,以及miR-200s在包涵囊肿形成、癌细胞生长、集体运动、血管生成、外泌体介导的细胞通讯和化疗反应中的多种作用。综上所述,miR-200s在卵巢癌的发生、发展和转移中发挥着重要作用,可能作为诊断生物标志物和治疗开发的靶点。