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长链非编码 RNA TPT1-AS1 的失调正向调节 QKI 的表达,并预测乳腺癌患者的预后不良。

Dyregulation of the lncRNA TPT1-AS1 positively regulates QKI expression and predicts a poor prognosis for patients with breast cancer.

机构信息

Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

Department of Oncological Surgery, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

出版信息

Pathol Res Pract. 2020 Nov;216(11):153216. doi: 10.1016/j.prp.2020.153216. Epub 2020 Sep 13.

Abstract

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 knockdown 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.

摘要

长链非编码 RNA(lncRNA)TPT1-AS1 已被报道参与多种癌症的发生。然而,其在乳腺癌(BC)中的临床价值、生物学功能及其潜在的分子机制尚不清楚。在本研究中,根据从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载的 RNA-seq 数据以及 qRT-PCR 结果,发现 TPT1-AS1 在 BC 组织中表达降低。此外,低 TPT1-AS1 表达与 BC 的一些恶性临床特征显著相关,如高 TNM 分期、淋巴结转移、Her-2 阴性和总生存期较短。更重要的是,单因素和多因素 Cox 回归分析表明,TPT1-AS1 是 BC 患者的独立预后因素。在 BC 细胞系中过表达和敲低 TPT1-AS1 分别通过细胞计数试剂盒-8(CCK-8)检测、划痕愈合检测和 Transwell 检测来改变其增殖、迁移和侵袭能力。此外,双荧光素酶活性报告实验验证了 TPT1-AS1 和 QKI 在 miR-330-3p 上共享一个结合位点。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。

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