Dyregulation of the lncRNA TPT1-AS1 positively regulates QKI expression and predicts a poor prognosis for patients with breast cancer
Dyregulation of the lncRNA TPT1-AS1 positively regulates QKI expression and predicts a poor prognosis for patients with breast cancer
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lncRNA TPT1-AS1 的失调可正向调节 QKI 表达并预测乳腺癌患者的不良预后
DOI：
10.1016/j.prp.2020.153216
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发表时间：
2020-11-01
影响因子：
2.8
通讯作者：
Li, Lihua
中科院分区：
文献类型：
--
作者：
Hu, Caixia;Fang, Kai;Li, Lihua
据报道，长非编码 RNA (lncRNA) TPT1-AS1 参与多种癌症的发生。然而，其在乳腺癌（BC）中的临床价值、生物学功能和潜在分子机制仍不清楚。在本研究中，基于从癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据库下载的 RNA-seq 数据，TPT1-AS1 表达在 BC 组织中降低，qRT-PCR 结果证实了上述发现。另外，低 TPT1-AS1 表达与恶性肿瘤的一些临床特征显着相关，例如高 TNM 分期、淋巴结转移、Her-2 阴性状态和较短的总生存期。更重要的是，单变量和多变量Cox回归分析表明TPT1-AS1是BC患者的独立预后因素。分别使用细胞计数试剂盒-8 (CCK-8) 测定、伤口愈合测定和 Transwell 测定测量，BC 细胞系中 TPT1-AS1 的过表达和敲低改变了它们的增殖、转移和侵袭。此外，双荧光素酶活性报告基因测定验证了 TPT1-AS1 和 QKI 在 miR-330-3p 中共享一个结合位点。基于这些发现，TPT1-AS1 可能代表 BC 患者的预后生物标志物，并通过 TPT1-AS1/miR-330-3p/QKI 轴参与 BC 的发展。
The long noncoding RNA (lncRNA) TPT1-AS1 has been reported to be involved in the development of multiple cancers. However, its clinical value, biological function, and underlying molecular mechanism in breast cancer (BC) remain unclear. In the present study, TPT1-AS1 expression was decreased in BC tissues, based on RNA-seq data download from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and the qRT-PCR results confirmed the above findings. Otherwise, low TPT1-AS1 expression was significantly associated with some clinical features of malignancy, such as high TNM stage, lymph node metastasis, a Her-2-negative status, and shorter overall survival. More importantly, univariate and multivariate Cox regression analyses indicated that TPT1-AS1 is an independent prognostic factor for patients with BC. Overexpression and knock-down of TPT1-AS1 in BC cell lines altered their proliferation, metastasis and invasion, as measured using the cell counting kit-8 (CCK-8) assay, wound-healing assay and transwell assay, respectively. In addition, a dual luciferase activity reporter assay validated that TPT1-AS1 and QKI shared a binding site in miR-330-3p. Based on these findings, TPT1-AS1 potentially represents a prognostic biomarker for patients with BC and participates in the development of BC through the TPT1-AS1/miR-330-3p/QKI axis.