Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated m6A modification

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine Pub Date : 2024-03-26 DOI:10.1111/jop.13531

Xiaoqing Chen, Renxiu Fan

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引用次数: 0

Abstract

Background

Inhibin A and N6-methyladenosine methylation modifications participate in oral squamous cell carcinoma development. However, the N6-methyladenosine modification of Inhibin A in oral squamous cell carcinoma has not been revealed. This study reveals a key gene “Inhibin A” that may affect the tumorigenesis of oral squamous cell carcinoma and its molecular mechanisms on N6-methyladenosine methyltransferase KIAA1429-mediated N6-methyladenosine methylation modification.

Methods

Bioinformatics analysis and quantitative real-time polymerase chain reaction identified the potential regulatory genes in oral squamous cell carcinoma. We examined the changes in the proliferation (Cell Counting Kit-8 assay), migration (transwell migration assay), and invasion (transwell invasion assays) of oral squamous cell carcinoma cells. We performed a xenograft tumor experiment to validate the role of Inhibin A in oral squamous cell carcinoma in vivo. The interactions between Inhibin A and KIAA1429 were analyzed using bioinformatics, methylated RNA immunoprecipitation-qPCR, quantitative real-time polymerase chain reaction, and Western blotting experiments.

Results

Inhibin A had the highest expression in patients with oral squamous cell carcinoma. Inhibin A silencing impaired the ability of oral squamous cell carcinoma cells to proliferate, migrate, and invade, as well as limited the tumorous growth of oral squamous cell carcinoma cells in vivo. Bioinformatics analysis showed that Inhibin A expression positively interacted with KIAA1429 expression in The Cancer Genome Atlas database. The levels were also upregulated in our clinical samples. Furthermore, KIAA1429 silencing repressed the N6-methyladenosine level of Inhibin A in oral squamous cell carcinoma.

Conclusions

Inhibin A promotes the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated N6-methyladenosine modification. This study adds to our current knowledge of the molecular mechanisms underlying oral squamous cell carcinoma malignancy.

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抑制素 A 通过 KIAA1429 介导的 m6A 修饰促进口腔鳞状细胞癌的肿瘤发生。

背景：抑制素 A 和 N6-甲基腺苷甲基化修饰参与了口腔鳞状细胞癌的发展。然而，Inhibin A 在口腔鳞状细胞癌中的 N6-甲基腺苷修饰尚未被揭示。本研究揭示了可能影响口腔鳞状细胞癌肿瘤发生的关键基因 "Inhibin A "及其在N6-甲基腺苷甲基转移酶KIAA1429介导的N6-甲基腺苷甲基化修饰的分子机制：生物信息学分析和定量实时聚合酶链反应确定了口腔鳞状细胞癌的潜在调控基因。我们检测了口腔鳞状细胞癌细胞的增殖（细胞计数试剂盒-8检测法）、迁移（经孔迁移检测法）和侵袭（经孔侵袭检测法）的变化。我们进行了异种移植肿瘤实验，以验证 Inhibin A 在体内口腔鳞状细胞癌中的作用。我们利用生物信息学、甲基化 RNA 免疫沉淀-qPCR、定量实时聚合酶链反应和 Western 印迹实验分析了 Inhibin A 与 KIAA1429 之间的相互作用：结果：抑制素 A 在口腔鳞状细胞癌患者中的表达量最高。结果表明：Inhibin A在口腔鳞状细胞癌患者中的表达量最高，沉默Inhibin A可抑制口腔鳞状细胞癌细胞的增殖、迁移和侵袭能力，并限制口腔鳞状细胞癌细胞在体内的肿瘤生长。生物信息学分析表明，在癌症基因组图谱数据库中，Inhibin A的表达与KIAA1429的表达呈正相关。在我们的临床样本中，其水平也出现了上调。此外，KIAA1429沉默抑制了口腔鳞状细胞癌中Inhibin A的N6-甲基腺苷水平：结论：抑制素 A 通过 KIAA1429 介导的 N6-甲基腺苷修饰促进口腔鳞状细胞癌的肿瘤发生。这项研究丰富了我们目前对口腔鳞状细胞癌恶性肿瘤分子机制的认识。

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

Journal of Oral Pathology & Medicine 医学-病理学

CiteScore

5.90

自引率

6.10%

发文量

121

审稿时长

4-8 weeks

期刊介绍： The aim of the Journal of Oral Pathology & Medicine is to publish manuscripts of high scientific quality representing original clinical, diagnostic or experimental work in oral pathology and oral medicine. Papers advancing the science or practice of these disciplines will be welcomed, especially those which bring new knowledge and observations from the application of techniques within the spheres of light and electron microscopy, tissue and organ culture, immunology, histochemistry and immunocytochemistry, microbiology, genetics and biochemistry.