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miR-299-5p 调控 FOXN3 的表达抑制口腔鳞状细胞癌细胞的增殖、迁移和侵袭。

FOXN3 Expression Regulated by miR-299-5p Inhibiting the Proliferation, Migration and Invasion of Oral Squamous Cell Carcinoma Cells.

机构信息

Department of Maxillofacial Surgery, People\'s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang, China.

Department of Plastic Surgery, People\'s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang, China.

出版信息

Protein Pept Lett. 2022;29(9):788-795. doi: 10.2174/0929866529666220816143538.

DOI:10.2174/0929866529666220816143538
PMID:35975858
Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) is one of the commonest malignancies of the oral cavity. FOXN3 is a tumor suppressor that represses the progression of many tumors. Nonetheless, its role in OSCC has not been elucidated. This work is performed to probe the role and dysregulation mechanism of FOXN3 in OSCC.

METHODS

FOXN3 mRNA and miR-299-5p expressions were quantified by quantitative real-time polymerase chain reaction (qRT-PCR); 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to detect OSCC cell growth; Transwell experiment was conducted to detect cell migration and invasion; dual-luciferase reporter experiment and bioinformatics were adopted to analyze the relationship between miR-299-5p and FOXN3; Western blot was implemented to detect FOXN3 protein expression.

RESULTS

FOXN3 expression was remarkably down-modulated, and miR-299-5p expression was markedly up-modulated in OSCC tissues and cell lines compared with paracancerous tissues and normal oral epithelial cell line. FOXN3 overexpression impeded OSCC cell growth, migration and invasion. FOXN3 was proven to be a downstream target of miR-299-5p, and miR-299-5p mimics enhanced OSCC cell growth, migration and invasion. Moreover, FOXN3 overexpression partially reversed the promoting effects of miR-299-5p mimics on OSCC cell growth, migration and invasion.

CONCLUSION

FOXN3 expression is remarkably down-modulated in OSCC tissues and cell lines, and miR-299-5p targets FOXN3 to facilitate OSCC cell growth, migration and invasion. These results imply that miR-299-5p/FOXN3 axis may be a potential target for OSCC treatment.

摘要

背景

口腔鳞状细胞癌(OSCC)是口腔最常见的恶性肿瘤之一。FOXN3 是一种肿瘤抑制因子,可抑制多种肿瘤的进展。然而,其在 OSCC 中的作用尚未阐明。本研究旨在探讨 FOXN3 在 OSCC 中的作用及其失调机制。

方法

采用实时定量聚合酶链反应(qRT-PCR)定量检测 FOXN3 mRNA 和 miR-299-5p 的表达;采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法检测 OSCC 细胞生长;采用 Transwell 实验检测细胞迁移和侵袭;采用双荧光素酶报告实验和生物信息学分析 miR-299-5p 与 FOXN3 之间的关系;采用 Western blot 检测 FOXN3 蛋白表达。

结果

与癌旁组织和正常口腔上皮细胞系相比,OSCC 组织和细胞系中 FOXN3 表达明显下调,miR-299-5p 表达明显上调。FOXN3 过表达抑制 OSCC 细胞生长、迁移和侵袭。FOXN3 被证实是 miR-299-5p 的下游靶基因,miR-299-5p 模拟物增强了 OSCC 细胞的生长、迁移和侵袭。此外,FOXN3 过表达部分逆转了 miR-299-5p 模拟物对 OSCC 细胞生长、迁移和侵袭的促进作用。

结论

FOXN3 在 OSCC 组织和细胞系中表达明显下调,miR-299-5p 靶向 FOXN3 促进 OSCC 细胞生长、迁移和侵袭。这些结果表明,miR-299-5p/FOXN3 轴可能是 OSCC 治疗的潜在靶点。

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