Role of hypoxia and embryonic stem cell genes in head and neck cancers

Yıl 2022, Cilt: 47 Sayı: 1, 7 - 15, 31.03.2022

Nermin Seda Ilgaz , Hale Öksüz , Mehmet Bertan Yılmaz , Nurşen Keser , Davut Alptekin

Öz

Purpose: The aim of this study was to determine the effect of hypoxia on HIF-1α, HIF-2α, SOX2, OCT4, NANOG, CD133, ESRRA genes in Hep-2 laryngeal and FaDu pharyngeal cancer cell lines.
Materials and Methods: Hep-2 and FaDu cell lines were exposed to hypoxia for 6, 12, 24, 48, and 72 hours to determine the effect of hypoxia and then treated with 5μM, 10μM and 20μM XCT790 under hypoxic conditions. Taqman Gene Expression Assays were used to determine mRNA expressions.
Results: In the hypoxic environment, we observed that HIF-2α, SOX2, OCT4, NANOG, CD133, and ESRRA mRNA expressions increased, except HIF-1α in Hep-2 cells. In FaDu cells, it was observed that HIF-1α and SOX2 mRNA expressions decreased, while HIF-2α, OCT4, NANOG, CD133, and ESRRA mRNA expressions increased. When cells were treated with the ESRRA inverse agonist XCT790, the hypoxia-induced gene expression profile was found altered.
Conclusion: In our study, it was determined that hypoxia changed the gene expression profile in Hep-2 and FaDu cell lines. According to our results, it was concluded that the ESRRA gene may be an important cofactor of the hypoxic response, but its inhibition alone may not be sufficient to abolish the hypoxic response. Protein data is needed to reveal the precise mechanisms of ESRRA and hypoxia association in head and neck cancers.

Anahtar Kelimeler

HIF, Head and neck cancers, hypoxia, embryonic stem cell marker, HIF

Baş boyun kanserlerinde hipoksi ve embriyonik kök hücre genlerinin rolü

Öz

Amaç: Bu çalışmada, Hep-2 larinks kanseri ve FaDu farenks kanseri hücre serilerinde hipoksinin, HIF-1α, HIF-2α, SOX2, OCT4, NANOG, CD133, ESRRA genleri üzerindeki etkisinin belirlenmesi amaçlanmıştır.
Gereç ve Yöntem: Hep-2 ve FaDu hücre hatları 6, 12, 24, 48 ve 72 saat süreyle hipoksiye maruz bırakılarak hipoksinin genler üzerindeki etkisi belirlendi daha sonra hücreler hipoksik koşullar altında 5μM, 10μM ve 20μM XCT790 ile muamele edildi. Genlerinin mRNA seviyeleri Taqman gen ekspresyon assayler kullanılarak belirlendi.
Bulgular: Hipoksik ortamda Hep-2 hücrelerinde HIF-1α dışında HIF-2α, SOX2, OCT4, NANOG, CD133 ve ESRRA mRNA ekspresyonlarının arttığını gözlemledik. FaDu hücrelerinde ise HIF-1α ve SOX2 mRNA ifadeleri azalırken, HIF-2α, OCT4, NANOG, CD133 ve ESRRA mRNA ifadelerinin arttığı gözlendi. Hücreler ESRRA invers agonisti XCT790 ile muamele edildiğinde, hipoksinin indüklediği gen ekspresyon profilinin değiştiği saptandı.
Sonuç: Çalışmamızda hipoksinin, Hep-2 ve FaDu hücre hatlarının gen ekspresyon profilini değiştirdiği saptanmıştır. Sonuçlarımıza göre, ESRRA geninin hipoksik yanıt oluşumunda önemli bir kofaktör olabileceği, ancak tek başına inhibisyonunun hipoksik yanıtı ortadan kaldırmak için yeterli olmayabileceği sonucuna varılmıştır. Baş ve boyun kanserlerinde ESRRA ve hipoksi ilişkisinin mekanizmalarını ortaya çıkarmak için protein verilerine ihtiyaç vardır.

Anahtar Kelimeler

hipoksi, HIF, Baş boyun kanserleri, hipoksi, embriyonik kök hücre marker, HIF

Kaynakça

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