Oral Squamous Hücreli Karsinomlarda SLC2A3/NLRP3 Aksının miR-22 ve miR-30e Aracılı Düzenlenmesi

Öz

Amaç: Bu araştırma, baş ve boyun kanserlerinde, özellikle oral skuamöz hücreli karsinomada (OSCC), SLC2A3 ve NLRP3 genlerinin düzenlenmesini inceleyerek, bu genlerin tümör progresyonundaki katkılarını ve belirli miRNA'ların düzenleyici etkilerini araştırmaktadır. Yöntem: HNSC’de SLC2A3 ve NLRP3 gen ekspresyonları, TCGA ve GTEx verileri ile GEPIA veritabanı kullanılarak analiz edilmiştir. Protein-protein etkileşimleri STRING veritabanı aracılığıyla tahmin edilmiş, miRNA-mRNA etkileşimleri ise miRDB kullanılarak incelenmiştir. RT-qPCR, OSCC’li 50 birey ve 6 sağlıklı kontrol grubundan elde edilen doku örneklerinde gen ekspresyonlarını analiz etmek için kullanılmış, miRNA seviyeleri TaqMan™ Advanced miRNA Assay kitleri ile ölçülmüştür. İstatistiksel analizler t-testleri, ANOVA ve Kaplan-Meier sağkalım analizi ile gerçekleştirilmiştir. Bulgular: SLC2A3 seviyeleri, HNSC tümör örneklerinde kanser dışı dokulara kıyasla belirgin şekilde yüksek bulunmuş (p = 0.01) ve tümör evreleri ile birlikte ilerleyen bir artış göstermiştir (p = 0.0059). NLRP3 ekspresyonu, HNSC’de yüksek bulunmuş (p = 0.01), ancak tümör progresyonu ile anlamlı bir ilişki gösterilmemiştir. OSCC’de ise hem SLC2A3 hem de NLRP3 ekspresyonları tümör evresi ile birlikte artmış ve güçlü bir şekilde birbirleriyle korele olmuştur (p < 0.0001). Yüksek NLRP3 kötü sağkalım oranları ile ilişkilendirilmiştir (p = 0.0001). miR-22 ve miR-30e seviyeleri, tümör progresyonu ile azalmış ve kötü sağkalım ile ilişkilendirilmiştir (p <0.01). Sonuç: SLC2A3 ve NLRP3, OSCC ve HNSC progresyonuna katkı sağlamaktadır ve bu etkiler HIF-1α yolu ile mediatör olabilir. miR-22 ve miR-30e bu genleri düzenler ve bu miRNA'ların kaybı, tümörün agresifliğini artırabilir, bu da OSCC için potansiyel terapötik hedefler sunmaktadır.

Anahtar Kelimeler

• Baş ve boyun skuamöz hücreli kanser
• Oral skuamöz hücreli kanser
• inflamasyon
• glukoz taşıyıcıları
• mikroRNA

miR-22 and miR-30e Mediated Regulation of the SLC2A3/NLRP3 Axis in Oral Squamous Cell Carcinomas

Öz

Objective: This research explores the regulation of SLC2A3 and NLRP3 genes in cancers of the head and neck region, including oral squamous cell carcinoma (OSCC), focusing on their contribution to tumor progression and the regulatory effects of specific miRNAs. Methods: SLC2A3 and NLRP3 gene expressions in HNSC were analyzed using the GEPIA database with TCGA and GTEx data. Protein-protein interactions were predicted via the STRING database, while miRNA-mRNA interactions were examined using miRDB. RT-qPCR was used to analyze gene expression in tissue samples obtained from 50 individuals with OSCC and 6 non-cancerous controls, while miRNA levels were measured using TaqMan™ Advanced miRNA Assays. Statistical analyses included t-tests, ANOVA, and Kaplan-Meier survival analysis. Results: SLC2A3 levels were markedly elevated in HNSC tumor samples relative to non-cancerous tissues (p = 0.01) and showed a progressive increase with advancing tumor stages (p = 0.0059). NLRP3 expression was found to be higher in HNSC (p = 0.01) without any significant association with tumor progression. In OSCC, both SLC2A3 and NLRP3 expressions increased with tumor stage and were strongly correlated (p < 0.0001). Elevated NLRP3 was associated with reduced survival rates (p = 0.0001). miR-22 and miR-30e levels decreased with tumor progression and were linked to poor survival (p <0.01). Conclusion: SLC2A3 and NLRP3 contribute to OSCC and HNSC progression, potentially mediated by the HIF-1α pathway. miR-22 and miR-30e regulate these genes, and their depletion may enhance tumor aggressiveness, representing potential therapeutic targets for OSCC.

Anahtar Kelimeler

• Oral squamous cell carcinoma
• Head and neck squamous cell carcinoma
• Inflammation
• Glucose transporters
• MicroRNA

Kaynakça

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