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MAFG-AS1/miR-150-5p/MYB 轴对乳腺癌细胞增殖和迁移的调控作用。

Regulatory effect of the MAFG‑AS1/miR‑150‑5p/MYB axis on the proliferation and migration of breast cancer cells.

机构信息

Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

出版信息

Int J Oncol. 2021 Jan;58(1):33-44. doi: 10.3892/ijo.2020.5150. Epub 2020 Nov 20.

Abstract

Long noncoding RNA (lncRNA) MAF BZIP transcription factor G antisense RNA 1 (MAFG‑AS1) has been demonstrated to serve an important role in the progression of various types of cancer, whereas its role in breast cancer has not been fully elucidated. The present study aimed to explore the potential role and underlying mechanism of MAFG‑AS1 in breast cancer. To achieve this, the expression of MAFG‑AS1, microRNA (miR)‑150‑5p and MYB was detected by reverse transcription‑quantitative PCR. The binding between miR‑150‑5p and MAFG‑AS1 or MYB was verified using a luciferase reporter assay. Cell proliferation was analyzed by MTS, apoptosis and cell cycle were detected by Annexin V/propidium iodide, and cell migration was analyzed by wound healing assay. The results demonstrated that the expression levels of MAFG‑AS1 were significantly upregulated in breast cancer tissues and cells compared with those in normal breast tissues and cells. High MAFG‑AS1 expression promoted the proliferation, migration and epithelial‑mesenchymal transition of breast cancer cells. By contrast, miR‑150‑5p expression was reduced in breast cancer tissues compared with that in healthy breast tissues, and low expression of miR‑150‑5p was associated with poor overall survival in patients with breast cancer. Bioinformatics and luciferase assay revealed that MAFG‑AS1 served as a sponge of miR‑150‑5p, and that miR‑150‑5p bound to MYB. The functional rescue assay results demonstrated that MAFG‑AS1 knockdown suppressed the proliferation and migration of breast cancer cells by regulating miR‑150‑5p, which in turn targeted MYB. In conclusion, the results of the present study demonstrated that MAFG‑AS1 functioned as a novel oncogenic lncRNA in the development of human breast cancer via regulating the miR‑150‑5p/MYB axis, which suggested that MAFG‑AS1 may be a novel biomarker for the diagnosis and prognosis of human breast cancer.

摘要

长链非编码 RNA(lncRNA)MAF BZIP 转录因子 G 反义 RNA 1(MAFG-AS1)已被证明在多种类型的癌症进展中发挥重要作用,但其在乳腺癌中的作用尚未完全阐明。本研究旨在探讨 MAFG-AS1 在乳腺癌中的潜在作用和机制。为此,采用逆转录定量 PCR 检测 MAFG-AS1、microRNA(miR)-150-5p 和 MYB 的表达。采用荧光素酶报告基因检测验证 miR-150-5p 与 MAFG-AS1 或 MYB 的结合。通过 MTS 分析细胞增殖,通过 Annexin V/碘化丙啶检测细胞凋亡和细胞周期,通过划痕愈合试验分析细胞迁移。结果表明,与正常乳腺组织和细胞相比,乳腺癌组织和细胞中 MAFG-AS1 的表达水平显著上调。高 MAFG-AS1 表达促进乳腺癌细胞的增殖、迁移和上皮-间充质转化。相比之下,与健康乳腺组织相比,乳腺癌组织中 miR-150-5p 的表达降低,并且乳腺癌患者中 miR-150-5p 表达水平低与总生存期不良相关。生物信息学和荧光素酶报告基因检测显示,MAFG-AS1 作为 miR-150-5p 的海绵,miR-150-5p 与 MYB 结合。功能挽救试验结果表明,通过调节 miR-150-5p,MAFG-AS1 敲低抑制乳腺癌细胞的增殖和迁移,而 miR-150-5p 靶向 MYB。综上所述,本研究结果表明,MAFG-AS1 通过调节 miR-150-5p/MYB 轴在人类乳腺癌的发生发展中发挥新型致癌 lncRNA 作用,提示 MAFG-AS1 可能成为人类乳腺癌诊断和预后的新型标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11b6/7721084/1fa56bd1b9ac/IJO-58-01-0033-g00.jpg

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