Epigenetic regulation of HOXA3 and its impact on oral squamous cell carcinoma progression

IF 2 3区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Oral Surgery Oral Medicine Oral Pathology Oral Radiology Pub Date : 2024-11-22 DOI:10.1016/j.oooo.2024.11.088

Kanaka Sai Ram Padam MSc , Dhanraj Salur Basavarajappa MSc , Naveena A N Kumar MS, MCh , Srikanth Gadicherla MDS , Sanjiban Chakrabarty PhD , Keith D Hunter BSc, BDS, FDS RCSEd, FDS RCS, PhD, FRCPath, FHEA , Raghu Radhakrishnan BDS, MDS, PhD, FRCPath(Res), FDTFEd

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引用次数: 0

Abstract

Objective

The role of homeobox A3 (HOXA3) in cancer progression is gaining prominence, however, to date, no studies have investigated its regulatory function in oral cancer. In this study, we explored the role of HOXA3 through epigenetic mechanisms.

Methods

Clinical samples were collected from 25 potentially malignant oral lesions and 50 oral squamous cell carcinoma (OSCC) patients, categorized into low-stage and high-stage tumors. The promoter activity of HOXA3 was determined through cloning and luciferase assays. CpG methylation patterns across the gene were identified using methyl-capture sequencing. Gene expression was analyzed using RT‒qPCR. The Survminer R package was used to assess the clinical significance of 3′ UTR methylation associated with overall survival. RNA‒RNA interactions were analyzed using RNAInter and TargetScan v8.0.

Results

HOXA3 expression was upregulated in dysplasia and downregulated in advanced cancer stages, showing an inverse correlation with promoter methylation, suggesting epigenetic regulation by DNA methylation. Hypermethylation of the 3′ UTR was associated with poor overall survival in advanced stages. Long noncoding RNAs and microRNAs may post-transcriptionally modulate HOXA3 in oral carcinogenesis.

Conclusion

CpG-specific hypermethylation in the 3′ UTR may serve as a potential biomarker in OSCC.

查看原文本刊更多论文

HOXA3的表观遗传调控及其对口腔鳞状细胞癌进展的影响。

目的：同源盒A3 （HOXA3）在癌症进展中的作用越来越突出，然而，迄今为止，还没有研究调查其在口腔癌中的调节功能。在本研究中，我们通过表观遗传机制探讨了HOXA3的作用。方法：收集25例口腔潜在恶性病变和50例口腔鳞状细胞癌（OSCC）患者的临床标本，将其分为低分期和高分期。通过克隆和荧光素酶测定HOXA3启动子活性。通过甲基捕获测序鉴定了该基因的CpG甲基化模式。RT-qPCR分析基因表达。Survminer R包用于评估3' UTR甲基化与总生存相关的临床意义。使用RNAInter和TargetScan v8.0分析RNA-RNA相互作用。结果：HOXA3在非典型增生中表达上调，在癌症晚期表达下调，与启动子甲基化呈负相关，提示其受DNA甲基化的表观遗传调控。3' UTR的高甲基化与晚期患者的总生存率较低有关。长链非编码rna和microrna可能在口腔癌发生过程中转录后调节HOXA3。结论：3' UTR中cpg特异性高甲基化可能是OSCC的潜在生物标志物。

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

Oral Surgery Oral Medicine Oral Pathology Oral Radiology DENTISTRY, ORAL SURGERY & MEDICINE-

CiteScore

3.80

自引率

6.90%

发文量

1217

审稿时长

2-4 weeks

期刊介绍： Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology is required reading for anyone in the fields of oral surgery, oral medicine, oral pathology, oral radiology or advanced general practice dentistry. It is the only major dental journal that provides a practical and complete overview of the medical and surgical techniques of dental practice in four areas. Topics covered include such current issues as dental implants, treatment of HIV-infected patients, and evaluation and treatment of TMJ disorders. The official publication for nine societies, the Journal is recommended for initial purchase in the Brandon Hill study, Selected List of Books and Journals for the Small Medical Library.