Liu Yingping, Chen Jinglong
Department of Obstetrics and Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University 251# Yaojia Yuan Road, Chaoyang District Beijing 100026 P. R. China.
Department of Oncology, Beijing Ditan Hospital, Capital Medical University Beijing 100015 PR China
RSC Adv. 2018 Dec 21;9(1):151-165. doi: 10.1039/c8ra08872a. eCollection 2018 Dec 19.
: EMT has a crucial effect on the progression and metastasis of tumors. This work will elucidate the role of miR-425 in EMT and the development of TNBC. : The differential miRNA expression among non-tumor, para-tumor (adjacent tissue of tumor) and tumor tissues was analyzed. The luciferase activities of TGF-β1 3'UTR treated with miR-425 were determined. Then human breast cancer cell lines were treated with mimics or inhibitors of miR-425, and then the cell proliferation and migration, and invasion ability were assessed. The expression of TGF-β1 and markers of epithelial cells and mesenchymal cells were analyzed. The influences of miR-425 on the development of TNBC through inducing EMT by targeting the TGF-β1/SMAD3 signaling pathway in TNBC cell lines were investigated. Furthermore, xenograft mice were used to explore the potential roles of miR-425 on EMT and the development of TNBC . : Compared with non-tumor tissues, 9 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. The relative expression of miR-425 in tumor tissues was obviously much lower than that in para-tumor and non-tumor tissues. MiR-425 suppressed TGF-β1 expression, and further inhibited expression of mesenchymal cell markers, while it exerted effects on cell proliferation and migration of TNBC cell lines. Moreover, the agomir of miR-425 could protect against the development process in a murine TNBC xenograft model. : Our results demonstrated that miR-425 targets TGF-β1, and was a crucial suppressor on EMT and the development of TNBC through inhibiting the TGF-β1/SMAD3 signaling pathway. This suggests that aiming at the TGF-β1/SMAD3 signaling pathway by enhancing relative miR-425 expression, is a feasible therapy strategy for TNBC.
上皮-间质转化（EMT）对肿瘤的进展和转移具有关键作用。本研究将阐明miR-425在上皮-间质转化及三阴性乳腺癌（TNBC）发展中的作用。分析非肿瘤组织、肿瘤旁组织（肿瘤相邻组织）和肿瘤组织中miRNA的差异表达。测定用miR-425处理的转化生长因子-β1（TGF-β1）3'非翻译区（3'UTR）的荧光素酶活性。然后用miR-425模拟物或抑制剂处理人乳腺癌细胞系，评估细胞增殖、迁移和侵袭能力。分析TGF-β1以及上皮细胞和间充质细胞标志物的表达。研究miR-425通过靶向TNBC细胞系中的TGF-β1/信号转导和转录激活因子3（SMAD3）信号通路诱导上皮-间质转化对TNBC发展的影响。此外，利用异种移植小鼠探索miR-425在上皮-间质转化及TNBC发展中的潜在作用。与非肿瘤组织相比，肿瘤组织中有9种miRNA上调，3种miRNA下调。miR-425在肿瘤组织中的相对表达明显低于肿瘤旁组织和非肿瘤组织。miR-425抑制TGF-β1表达，并进一步抑制间充质细胞标志物的表达，同时对TNBC细胞系的细胞增殖和迁移产生影响。此外，miR-425激动剂可在小鼠TNBC异种移植模型中抵御疾病发展进程。我们的结果表明，miR-425靶向TGF-β1，通过抑制TGF-β1/SMAD3信号通路，是上皮-间质转化及TNBC发展的关键抑制因子。这表明通过增强miR-425相对表达靶向TGF-β1/SMAD3信号通路，是TNBC的一种可行治疗策略。
