MiR-125b-5p/STAT3 Axis Regulates Drug Resistance in Osteosarcoma Cells by Acting on ABC Transporters.

IF 3.8 3区医学 Q2 CELL & TISSUE ENGINEERING

Stem Cells International Pub Date : 2023-04-29 eCollection Date: 2023-01-01 DOI:10.1155/2023/9997676

Yang Yang, Yueyuan Chen, Jiajia Liu, Bo Zhang, Linlin Yang, Jianhua Xue, Zexu Zhang, Lili Qin, Rongpeng Bian

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Abstract

Background: The poor prognosis of the highly malignant tumor osteosarcoma stems from its drug resistance and therefore exploring its resistance mechanisms will help us identify more effective treatment options. However, the effects of miR-125b-5p on drug resistance in osteosarcoma cells are still unclear.

Methods: To study the effects of miR-125b-5p on drug resistance in osteosarcoma cells. Osteosarcoma-resistant miR-125b-5p was obtained from the databases GeneCards and g:Profiler. CCK8, western blot, and transwell were applied for the detection of the miR-125b-5p effects on proliferation, migration, invasion, apoptosis, and drug resistance in osteosarcoma. Bioinformatics is aimed at demonstrating the targeting factor miR-125b-5p, performing protein interaction enrichment analysis by Metascape, and finally validating by binding sites.

Results: Upregulation of miR-125b-5p restrains proliferation, migration, and invasion of osteosarcoma and promotes apoptosis. In addition, miR-125b-5p can restore drug sensitivity in drug-resistant osteosarcoma. miR-125-5p restrains the signal transducer and inhibits the transcription 3 (STAT3) expression activator via targeting its 3'-UTR. STAT3 affects drug-resistant osteosarcoma to regulate the ABC transporter.

Conclusion: miR-125b-5p/STAT3 axis mediates the drug resistance of osteosarcoma by acting on ABC transporter.

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MiR-125b-5p/STAT3 轴通过作用于 ABC 转运体调节骨肉瘤细胞的耐药性

背景：高度恶性肿瘤骨肉瘤的不良预后源于其耐药性，因此探索其耐药机制将有助于我们找到更有效的治疗方案。然而，miR-125b-5p 对骨肉瘤细胞耐药性的影响尚不清楚：方法：研究 miR-125b-5p 对骨肉瘤细胞耐药性的影响。从数据库 GeneCards 和 g:Profiler 中获取骨肉瘤耐药 miR-125b-5p。应用 CCK8、Western 印迹和 transwell 检测 miR-125b-5p 对骨肉瘤细胞增殖、迁移、侵袭、凋亡和耐药性的影响。生物信息学的目的是证明miR-125b-5p的靶向因子，利用Metascape进行蛋白质相互作用富集分析，最后通过结合位点进行验证：结果：miR-125b-5p 的上调可抑制骨肉瘤的增殖、迁移和侵袭，并促进其凋亡。此外，miR-125b-5p 还能恢复耐药骨肉瘤的药物敏感性。miR-125-5p 通过靶向 3'-UTR 抑制信号转导抑制转录 3（STAT3）表达激活因子。结论：miR-125b-5p/STAT3轴通过作用于ABC转运体介导骨肉瘤的耐药性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cells International CELL & TISSUE ENGINEERING-

CiteScore

8.10

自引率

2.30%

发文量

188

审稿时长

18 weeks

期刊介绍： Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials. Topics covered include, but are not limited to: embryonic stem cells; induced pluripotent stem cells; tissue-specific stem cells; stem cell differentiation; genetics and epigenetics; cancer stem cells; stem cell technologies; ethical, legal, and social issues.