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miR-125a-5p 通过靶向 ERBB3 抑制头颈部癌症中的细胞增殖、细胞周期进程和迁移,同时促进细胞凋亡。

MiR-125a-5p inhibits cell proliferation, cell cycle progression, and migration while promoting apoptosis in head and neck cancers by targeting ERBB3.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China; The Second School of Clinical Medicine, Southern Medical University.

Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.

出版信息

Auris Nasus Larynx. 2021 Jun;48(3):477-486. doi: 10.1016/j.anl.2020.10.001. Epub 2020 Oct 16.

Abstract

OBJECTIVE

Head and neck cancer is one of the most common cancer types worldwide. MicroRNAs play a vital regulatory role in the occurrence and development of cancer. The objective of this study is to explore the mechanism of miR-125a-5p in the proliferation, migration and apoptosis of head and neck cancer cells and define its target genes.

METHODS

The effects of miR-125a-5p on head and neck cancer cells proliferation, cell cycle distribution, apoptosis and migration were evaluated by colony formation, BrdU assay, flow cytometry and transwell assays. The potential target gene of miR-125a-5p was determined by luciferase activity assay and western blot analysis.

RESULTS

In this study, overexpression of miR-125a-5p significantly inhibited the proliferation of head and neck cancer cells, whereas inhibition of miR-125a-5p enhanced their proliferation. BrdU assay and flow cytometry revealed that miR-125a-5p might inhibit the proliferation of cancer cells by causing cell cycle arrest. Cell apoptosis assay and Transwell assay indicated that miR-125a-5p induced cell apoptosis and inhibited cell migration of cancer cells. Other experiments confirmed that miR-125a-5p could significantly downregulate its expression by binding to ERBB3 to inhibit proliferation and ERBB3 could at least partially mediate the inhibition of miR-125a-5p on the proliferation of head and neck cancer cells.

CONCLUSION

The findings of this study suggested that the miR-125a-5p/ERBB3 axis might play a role in the proliferation, regulation of cell cycle, migration and apoptosis of head and neck cancer cells, potentially offering a new target for treatments of head and neck cancers.

摘要

目的

头颈部癌症是全球最常见的癌症类型之一。microRNAs 在癌症的发生和发展中发挥着重要的调节作用。本研究旨在探讨 miR-125a-5p 在头颈部癌细胞增殖、迁移和凋亡中的作用机制及其靶基因。

方法

通过集落形成、BrdU 检测、流式细胞术和 Transwell 实验评估 miR-125a-5p 对头颈部癌细胞增殖、细胞周期分布、凋亡和迁移的影响。通过荧光素酶活性测定和 Western blot 分析确定 miR-125a-5p 的潜在靶基因。

结果

本研究中,miR-125a-5p 的过表达显著抑制了头颈部癌细胞的增殖,而 miR-125a-5p 的抑制则增强了其增殖。BrdU 检测和流式细胞术表明,miR-125a-5p 可能通过引起细胞周期停滞来抑制癌细胞的增殖。细胞凋亡实验和 Transwell 实验表明,miR-125a-5p 诱导癌细胞凋亡并抑制其迁移。其他实验证实,miR-125a-5p 可通过与 ERBB3 结合显著下调其表达,从而抑制增殖,而 ERBB3 至少可部分介导 miR-125a-5p 对头颈部癌细胞增殖的抑制作用。

结论

本研究结果表明,miR-125a-5p/ERBB3 轴可能在头颈部癌细胞的增殖、细胞周期调控、迁移和凋亡中发挥作用,为头颈部癌症的治疗提供了新的靶点。

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