Department of Stomatology, The Sixth Hospital of Wuhan Affiliated Hospital of Jianghan University, Wuhan, Hubei, China.
Department of Stomatology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China.
J Oral Pathol Med. 2024 Apr;53(4):266-274. doi: 10.1111/jop.13531. Epub 2024 Mar 26.
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.
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.
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.
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.
抑制素 A 和 N6-甲基腺苷修饰参与口腔鳞状细胞癌的发展。然而，口腔鳞状细胞癌中抑制素 A 的 N6-甲基腺苷修饰尚未被揭示。本研究揭示了一个关键基因“抑制素 A”，它可能影响口腔鳞状细胞癌的肿瘤发生及其在 N6-甲基腺苷甲基转移酶 KIAA1429 介导的 N6-甲基腺苷甲基化修饰上的分子机制。
生物信息学分析和实时定量聚合酶链反应鉴定了口腔鳞状细胞癌中的潜在调节基因。我们检测了口腔鳞状细胞癌细胞增殖（细胞计数试剂盒-8 检测）、迁移（transwell 迁移检测）和侵袭（transwell 侵袭检测）的变化。我们进行了异种移植肿瘤实验来验证抑制素 A 在体内对口腔鳞状细胞癌的作用。利用生物信息学、甲基化 RNA 免疫沉淀-qPCR、实时定量聚合酶链反应和 Western blot 实验分析抑制素 A 与 KIAA1429 之间的相互作用。
在口腔鳞状细胞癌患者中，抑制素 A 的表达最高。抑制素 A 沉默削弱了口腔鳞状细胞癌细胞增殖、迁移和侵袭的能力，并限制了口腔鳞状细胞癌细胞在体内的肿瘤生长。生物信息学分析显示，在 The Cancer Genome Atlas 数据库中，抑制素 A 表达与 KIAA1429 表达呈正相互作用。我们的临床样本中也上调了这两种水平。此外，KIAA1429 沉默抑制了口腔鳞状细胞癌中抑制素 A 的 N6-甲基腺苷水平。
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。本研究增加了我们对口腔鳞状细胞癌恶性分子机制的认识。
