Wang Ling, Wu Xiaotong, Wang Bowei, Wang Qiang, Han Liying
Department of Obstetrics and Gynecology, The Second Hospital of Jilin UniversityChangchun, China.
Am J Transl Res. 2017 Jul 15;9(7):3443-3451. eCollection 2017.
MicroRNA-145 (miR-145) can regulate tumor cell invasion, metastasis, apoptosis, proliferation and stem cell differentiation. However, the molecular mechanisms of miR-145 used to regulate ovarian invasion and metastasis remain to be determined. In this study, Transwell cell migration and wound healing assays were used to detect the effects of miR-145 upregulation on ovarian carcinoma cell invasion and metastasis, respectively. The MUC1 expression vector, together with quantitative real-time PCR and Western blotting, was used to investigate the effects of miR-145 on E-cadherin (E-cad)-induced cell invasion and the related molecular mechanisms. The results showed that miR-145 mimics could inhibit SKOV3 cell invasion and metastasis. MiR-145 inhibited mucin 1 (MUC1) post-transcriptional expression by binding to its 3'-untranslated region. The epithelial mesenchymal transition marker E-cad, which is a downstream molecule of MUC1, was promoted by miR-145 overexpression. Furthermore, the E-cad protein level was inversely correlated with MUC1 expression in SKOV3 cells. These observations indicated that promotion of E-cad signaling induced by miR-145 was restrained by MUC1 inhibition. Thus, miR-145 may serve as a tumor suppressor which can downregulate E-cad expression by targeting MUC1, leading to the inhibition of tumor invasion and metastasis. Using miR-145 mimics may be a rational approach for therapeutic applications in ovarian carcinoma in the future.
微小RNA-145（miR-145）可调节肿瘤细胞的侵袭、转移、凋亡、增殖及干细胞分化。然而，miR-145用于调节卵巢癌侵袭和转移的分子机制仍有待确定。在本研究中，分别采用Transwell细胞迁移实验和伤口愈合实验检测上调miR-145对卵巢癌细胞侵袭和转移的影响。利用MUC1表达载体，结合定量实时聚合酶链反应和蛋白质免疫印迹法，研究miR-145对E-钙黏蛋白（E-cad）诱导的细胞侵袭及相关分子机制的影响。结果显示，miR-145模拟物可抑制SKOV3细胞的侵袭和转移。miR-145通过与黏蛋白1（MUC1）的3'-非翻译区结合，抑制其转录后表达。miR-145过表达可促进MUC1的下游分子——上皮间质转化标志物E-cad的表达。此外，SKOV3细胞中E-cad蛋白水平与MUC1表达呈负相关。这些观察结果表明，miR-145诱导的E-cad信号通路的激活受到MUC1抑制的限制。因此，miR-145可能作为一种肿瘤抑制因子，通过靶向MUC1下调E-cad表达，从而抑制肿瘤的侵袭和转移。未来，使用miR-145模拟物可能是卵巢癌治疗应用的一种合理方法。
