İnsan HTR1B İfadesinin İnsan Hücre Hatlarında ve Ortoloğu Ser-4’ün Caenorhabditis elegans’da Hipoksik Koşullarda Cevabının Deneysel ve In silico İncelenmesi

Öz

Serotonin ve serotonin reseptörleri ile kanser arasındaki ilişki son yıllarda özellikle araştırılmıştır. Bazı çalışmalar, serotonin reseptörlerinin kanser hücrelerinin büyümesini, yayılmasını ve metastazını destekleyebileceğini ileri sürmektedir. Serotonin ayrıca C. elegans'ta önemli bir rol oynar. Bu organizmada serotonin, sinir sistemi ve diğer dokulardaki çeşitli fizyolojik süreçlerin düzenlenmesinde kullanılan bir nörotransmitter olarak işlev görür. C. elegans, serotonin sisteminin evrimsel olarak oldukça korunduğunu ve insanlarda benzer biyolojik işlevlere sahip olduğunu göstermektedir. Hücrelerdeki oksijen seviyelerinde azalmaya hipoksi denir ve bazı klinik çalışmalar hipoksinin tümör büyümesini desteklediğini ve tedavi direnciyle ilişkili olduğunu göstermiştir. HIF, oksijen seviyelerindeki değişikliklere yanıt olarak gen ekspresyonunu düzenler ve hipoksi koşulları altında hücrelerin yanıt verdiği DNA'nın belirli bölgelerine bağlanarak gen ekspresyonunu etkiler. Hipoksik çalışmalarda kanserle ilişkili genlerin araştırılmasında yeni bir model olarak C. elegans'ın kullanılabilirliği önemlidir. Bu amaçla iki farklı modelde (insan hücre hatları (HUVEC ve PC-3) ve C. elegans) hipoksik koşullar oluşturuldu ve son yıllarda kanserle ilişkili olduğu belirlenen serotonin reseptörleri HTR1B ve onun ortologu Ser-4'ün ekspresyon değişiklikleri incelendi. Yapılan biyoinformatik analizlerde bu iki genin %87 benzer olduğu ve benzer hücresel sinyal yollarını etkilediği görülmüştür. HTR1B'nin hipoksik koşullarda 48 ve 72. saatlerde HUVEC hücre hattında ekspresyonunun normal koşullara kıyasla arttığını bulduk. PC-3 hücre hattında ise 48. saatte hipoksik yanıt gözlendi. HTR1B C. elegans ortolog geni olan Ser-4'ün ekspresyonu da 1. saatte hipokside artmıştır. HTR1B geninin çeşitli hücre hatları üzerindeki etkileri, serotoninerjik sistemin karmaşık dinamiklerini anlamada kritik bir rol oynamaktadır. Sonuç olarak, HTR1B geninin çeşitli hücre hatları üzerindeki etkileri, bu genin kanserdeki işlevselliğini ve potansiyel terapötik kullanımlarını anlamada önemli bir adım oluşturmaktadır.

Anahtar Kelimeler

• Serotonin
• HTR1B
• Ser-4
• HUVEC
• PC-3
• C.elegans
• Kanser
• Hipoksi

Experimental and In silico Analysis of the Hypoxic Response of Human HTR1B Expression in Human Cell Lines and Its Ortholog Ser-4 Expression in Caenorhabditis elegans

Öz

The relationship between serotonin receptors and cancer has been particularly investigated in recent years. Some studies suggest that serotonin receptors may promote the growth, spread, and metastasis of cancer cells. Serotonin also plays an important role in C. elegans. The simple nervous system of C. elegans provides an ideal system to study to understand the functions of neurons and neuromodulators. The Serotonin system is highly conserved evolutionarily in humans and C. elegans. A decrease in oxygen levels in cells is called hypoxia and hypoxia promotes tumor growth and is associated with treatment resistance. The usability of C. elegans as a new model in the investigation of cancer-related genes in hypoxic studies is important. For this purpose, hypoxic conditions were created in two different models (human cell lines (HUVEC and PC-3) and C. elegans) and the expression changes of serotonin receptors HTR1B and its ortholog Ser-4 were examined. Bioinformatic analyses showed that these two genes were 87% similar and affected similar cellular signaling pathways. The expression of HTR1B was increased in the HUVEC cell line at 48 and 72 hours under hypoxic conditions. A hypoxic response was observed in the PC-3 cell line at 48 hours. The expression of Ser-4, the HTR1B C. elegans ortholog gene, was also increased in hypoxia at 1 hour. The effects of the HTR1B gene on various cell lines play a critical role in understanding the complex dynamics of the serotonergic system. In conclusion, the effects of the HTR1B gene on various cell lines constitute an important step in understanding the functionality of this gene in cancer and its potential therapeutic uses.

Anahtar Kelimeler

• Serotonin
• HTR1B
• Ser-4
• HUVEC
• PC-3
• C.elegans
• Cancer
• Hypoxia

Kaynakça

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