ChangJiang Scholar's Laboratory, Shantou University Medical College (SUMC), 515041, Shantou, Guangdong, China.
The Cancer Center, Xiang'an Hospital of Xiamen University, 2000 East Xiang'an Rd., Xiang'an, Xiamen, China.
Cell Death Dis. 2018 Dec 5;9(12):1171. doi: 10.1038/s41419-018-1210-9.
Recent studies indicate that the long noncoding RNA ATB (lncATB) can induce the epithelial-mesenchymal transition (EMT) in cancer cells, but the specific cellular targets of lncATB require further investigation. In the present study, the upregulation of lncATB in breast cancer cells was validated in a TGF-β-induced EMT model. Gain- and loss-of-function studies demonstrated that lncATB enhanced cell migration, invasion and clonogenicity in vitro and in vivo. LncATB promoted the EMT by acting as a sponge for the miR-200 family and restoring Twist1 expression. Subsequently, the clinical significance of lncATB was investigated in a cohort of breast cancer patients (N = 131). Higher lncATB expression was correlated with increased nodal metastasis (P = 0.036) and advanced clinical stage (P = 0.011) as well as shorter disease-free survival (P = 0.043) and overall survival (P = 0.046). These findings define Twist1 as a major target of lncATB in the induction of the EMT and highlight lncATB as a biomarker in breast cancer patients.
最近的研究表明,长链非编码 RNA ATB(lncATB)可以诱导癌细胞发生上皮-间充质转化(EMT),但 lncATB 的具体细胞靶标仍需要进一步研究。在本研究中,在 TGF-β诱导的 EMT 模型中验证了乳腺癌细胞中 lncATB 的上调。增益和缺失功能研究表明,lncATB 增强了体外和体内细胞的迁移、侵袭和克隆形成能力。lncATB 通过充当 miR-200 家族的海绵并恢复 Twist1 表达来促进 EMT。随后,在一组乳腺癌患者(N=131)中研究了 lncATB 的临床意义。较高的 lncATB 表达与淋巴结转移增加(P=0.036)、临床分期较晚(P=0.011)以及无病生存期(P=0.043)和总生存期(P=0.046)缩短相关。这些发现将 Twist1 定义为 lncATB 诱导 EMT 的主要靶标,并强调 lncATB 是乳腺癌患者的生物标志物。