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miR-301b 和 NR3C2 共同调节细胞的恶性特征,并且有可能成为乳腺癌的独立预后因素。

miR-301b and NR3C2 co-regulate cells malignant properties and have the potential to be independent prognostic factors in breast cancer.

机构信息

Department of Breast and Thyroid Surgery, People's Hospital of Ganzhou City, Ganzhou, China.

Department of Anesthesiology, People's Hospital of Ganzhou City, Ganzhou, China.

出版信息

J Biochem Mol Toxicol. 2021 Feb;35(2):e22650. doi: 10.1002/jbt.22650. Epub 2020 Oct 15.

Abstract

This study intends to address the function of miR-301b/nuclear receptor subfamily 3 group C member 2 (NR3C2) in breast cancer. The Cancer Genome Atlas database was processed to investigate the expression of miR-301b/NR3C2 in breast cancer samples, as well as the relationship between their expression and the prognosis of the patients. Cox regression analysis was performed to determine whether miR-301b/NR3C2 was an independent predictor of the patient's prognosis. Associations between miR-301b and NR3C2 were analyzed by prediction website, dual-luciferase assay, and Pearson correlation coefficient. Quantitative polymerase chain reaction and Western blot analyses were implemented to detect gene expression. The relevant biological characteristics of MCF7 and BCAP-37 cells were tested by cell counting kit-8, colony formation, and transwell assays. Lower expression of NR3C2, which was closely related to the bad prognosis of breast cancer patients, was presented in breast cancer samples and can be used as an independent predictor. miR-301b, as an upstream regulator of NR3C2, was highly expressed in breast cancer samples and can be used as an independent predictor as well. Notably, a higher level of miR-301b and lower level of NR3C2 were related to the reduced overall survival in patients with breast cancer. The proliferative and migratory behaviors of cells were elevated or blocked after overexpression of miR-301b or NR3C2, respectively. However, the above situation was attenuated after together upregulation of miR-301b and NR3C2. The present data afforded evidence that miR-301b may be a tumor-promoting miRNA in breast cancer, and that miR-301b/NR3C2 axis mediated tumor development from cell proliferation and migration.

摘要

本研究旨在探讨 miR-301b/核受体亚家族 3 组 C 成员 2(NR3C2)在乳腺癌中的作用。利用癌症基因组图谱数据库分析乳腺癌样本中 miR-301b/NR3C2 的表达情况及其与患者预后的关系。采用 Cox 回归分析确定 miR-301b/NR3C2 是否为患者预后的独立预测因子。通过预测网站、双荧光素酶报告基因实验和 Pearson 相关系数分析 miR-301b 与 NR3C2 之间的相关性。采用定量聚合酶链反应和 Western blot 分析检测基因表达。通过细胞计数试剂盒-8、集落形成和 Transwell 实验检测 MCF7 和 BCAP-37 细胞的相关生物学特性。结果表明,NR3C2 表达下调与乳腺癌患者预后不良密切相关,可作为独立预测因子。miR-301b 作为 NR3C2 的上游调节因子,在乳腺癌样本中呈高表达,也可作为独立预测因子。值得注意的是,miR-301b 水平较高和 NR3C2 水平较低与乳腺癌患者总生存期缩短相关。过表达 miR-301b 或 NR3C2 分别可增强或阻断细胞的增殖和迁移行为,但同时上调 miR-301b 和 NR3C2 则可减弱上述情况。综上所述,本研究数据表明,miR-301b 可能是乳腺癌中的一种促瘤 miRNA,miR-301b/NR3C2 轴介导了细胞增殖和迁移促进肿瘤发生。

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