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长链非编码 RNA TUG1 的下调与乳腺癌细胞的增殖、迁移和侵袭有关。

Downregulation of the long non-coding RNA TUG1 is associated with cell proliferation, migration, and invasion in breast cancer.

机构信息

Department of Breast Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, Jilin, 130033, PR China.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin, 130012, PR China.

出版信息

Biomed Pharmacother. 2017 Nov;95:1636-1643. doi: 10.1016/j.biopha.2017.09.076. Epub 2017 Oct 6.

Abstract

Recent studies have identified many long non-coding RNAs (lncRNAs) with critical roles in various biological processes including tumorigenesis. Taurine-upregulated gene 1 (TUG1), is an lncRNA recently reported to be involved in the progression of several human cancers. This study aimed to investigate the clinical significance and biological functions of TUG1 in breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure TUG1 expression in cells from breast cancer cell lines and in 58 matched pairs of breast cancer and normal tissue samples from patients with clinicopathological comparisons. Gain-and loss-of-function experiments were performed in vitro to investigate the biological role of TUG1. TUG1 expression was significantly downregulated in both breast cancer tissues and cell lines compared to controls, and low TUG1 expression was significantly correlated with mutant p53 expression (p=0.037) and lymph node metastasis (p=0.044). In vitro experiments revealed that TUG1 overexpression significantly suppressed cell proliferation by causing cell cycle arrest and inducing apoptosis in breast cancer cells, while TUG1 knockdown caused increased cell growth via promoting cell cycle progression and regulating the expression of cyclinD1 and CDK4. Further functional assays indicated that TUG1 overexpression significantly promoted cell migration and invasion while TUG1 knockdown had the opposite effects. Our findings indicate that the lncRNA TUG1 is a tumor suppressor in breast cancer, and may serve as a novel prognostic biomarker and potential therapeutic target for patients with breast cancer.

摘要

最近的研究已经确定了许多长链非编码 RNA(lncRNA)在包括肿瘤发生在内的各种生物学过程中具有关键作用。牛磺酸上调基因 1(TUG1)是一种最近报道的 lncRNA,参与多种人类癌症的进展。本研究旨在探讨 TUG1 在乳腺癌中的临床意义和生物学功能。通过定量实时聚合酶链反应(qRT-PCR)测量了来自乳腺癌细胞系的细胞和来自具有临床病理比较的 58 对乳腺癌和正常组织样本中的 TUG1 表达。在体外进行了增益和功能丧失实验,以研究 TUG1 的生物学作用。与对照相比,乳腺癌组织和细胞系中 TUG1 的表达均明显下调,并且低 TUG1 表达与突变型 p53 表达(p=0.037)和淋巴结转移(p=0.044)显著相关。体外实验表明,TUG1 过表达通过导致细胞周期停滞和诱导乳腺癌细胞凋亡,显著抑制细胞增殖,而 TUG1 敲低通过促进细胞周期进程和调节细胞周期蛋白 D1 和 CDK4 的表达导致细胞生长增加。进一步的功能测定表明,TUG1 过表达显著促进细胞迁移和侵袭,而 TUG1 敲低则具有相反的作用。我们的研究结果表明,lncRNA TUG1 是乳腺癌中的肿瘤抑制因子,可能作为乳腺癌患者的新型预后生物标志物和潜在治疗靶标。

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