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, Dhanraj Salur Basavarajappa, Naveena A N Kumar, Srikanth Gadicherla, Sanjiban Chakrabarty, Keith D Hunter, Raghu Radhakrishnan

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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.

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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.