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miR-150 低表达与乳腺癌患者致癌途径的激活和预后不良相关。

Low microRNA150 expression is associated with activated carcinogenic pathways and a poor prognosis in patients with breast cancer.

机构信息

Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, P.R. China.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

出版信息

Oncol Rep. 2021 Mar;45(3):1235-1248. doi: 10.3892/or.2021.7945. Epub 2021 Jan 21.

Abstract

Breast cancer is the most common type of cancer amongst women worldwide, and numerous microRNAs (miRNAs/miRs) are involved in the initiation and progression of breast cancer. The aim of the present study was to identify hub miRNAs and determine the underlying mechanisms regulated by these miRNAs in breast cancer. Breast invasive carcinoma transcriptome data (including mRNAs and miRNAs), and clinical data were acquired from The Cancer Genome Atlas database. Differential gene expression analysis, co‑expression network analysis, gene set enrichment analysis (GSEA) and prognosis analysis were used to screen the hub miRNAs and explore their functions. Functional experiments were used to determine the underlying mechanisms of the hub miRNAs in breast cancer cells. The results revealed that low miR150 expression predicted a more advanced disease stage, and was associated with a less favorable prognosis. Through the combined use of five miRNA‑target gene prediction tools, 31 potential miR150 target genes were identified. GSEA revealed that low miR150 expression was associated with the upregulation of several cancer‑associated signaling pathways, and the downregulation of several tumor suppressor genes. Furthermore, miR150 independently affected overall survival in patients, and interacted with its target genes to indirectly affect overall and disease‑free survival. Functional experiments demonstrated that miR150 positively regulated B and T lymphocyte attenuator (BTLA), and the downregulation of miR150 and BTLA combined promoted cell migration. In conclusion, the present study revealed that low miR150 expression was associated with less favorable clinical features, upregulation of several carcinogenic signaling pathways, and poor patient survival. Additionally, a miR150‑BTLA axis was suggested to regulate cell viability and migration.

摘要

乳腺癌是全球女性中最常见的癌症类型,许多 microRNAs(miRNAs/miRs)参与乳腺癌的发生和发展。本研究旨在鉴定 hub miRNAs,并确定这些 miRNAs 调节乳腺癌的潜在机制。从癌症基因组图谱数据库中获取乳腺癌浸润性癌转录组数据(包括 mRNAs 和 miRNAs)和临床数据。采用差异基因表达分析、共表达网络分析、基因集富集分析(GSEA)和预后分析筛选 hub miRNAs,并探讨其功能。通过功能实验确定 hub miRNAs 在乳腺癌细胞中的潜在机制。结果表明,miR150 表达水平低预示着疾病分期更晚,且与预后不良相关。通过联合使用五种 miRNA 靶基因预测工具,鉴定出 31 个潜在的 miR150 靶基因。GSEA 结果显示,miR150 表达水平低与多种癌症相关信号通路的上调以及多个肿瘤抑制基因的下调有关。此外,miR150 独立影响患者的总生存率,并且与靶基因相互作用间接影响总生存率和无病生存率。功能实验表明,miR150 正向调节 B 和 T 淋巴细胞衰减因子(BTLA),下调 miR150 和 BTLA 联合促进细胞迁移。综上所述,本研究表明 miR150 表达水平低与临床特征不良、多种致癌信号通路的上调以及患者生存率低有关。此外,miR150-BTLA 轴可能调节细胞活力和迁移。

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