Çağrı Öner, Ertuğrul Çolak, Necdet Altıner

Hepatoselüler karsinom tedavisi için etkili terapötikler PIWI Interacting RNA ifadelerini nasıl değiştirir?

Amaç: PIWI interacting RNA’lar (piRNA’lar) herhangi bir protein üretemeyen ancak hücrelerin transkripsiyon ve transkripsiyon sonrası mekanizmalarında etkili olan küçük kodlayıcı olmayan RNA'ların yeni üyeleridir. Günümüzde, kanser hücrelerinin tedavisinde kimyasal bileşikler yerine, hem doğal bileşikler hem de vitaminler uygulanabilirliği araştırılmaktadır. Bu çalışmadaki amacımız, 4-Hidroksikoumarinin ve aktif D vitamini formunun (1.25-dihidroksivitamin D) hepatoselüler karsinomada piRNA'ların olası ekspresyonları üzerindeki değişiklikleri belirlemektir. Yöntemler: Önceki çalışmamızdan elde edilen verilere göre, optimal zaman ve konsantrasyonu belirlenen 4-Hidroksikoumarin, 1.25-dihidroksivitamin D ve D vitamininin ilaç formu HePG2 hücrelerine uygulandı. Uygulamadan sonra total RNA izole edildi. piR-Hep-1 ve piR-651'in ekspresyonları Gerçek Zamanlı Polimeraz Zincir Reaksiyonları kullanılarak belirlendi. Bulgular: Elde edilen verilere göre, 4-Hidroksikoumarin uygulanan HePG2 hücrelerinde kontrole göre piR-651 ekspresyonunda istatistiksel olarak anlamlı bir artış gözlenmiştir (p< 0.001). Bununla birlikte, 4-Hidroksikoumarin uygulamasından sonra piR-Hep-1 ekspresyonundaki değişim istatistiksel olarak anlamlı değildir (p> 0.05). Buna karşılık, 1,25- dihidroksivitamin uygulaması HePG2 hücrelerinde piRHep-1 ekspresyonunu istatistiksel olarak anlamlı şekilde azaltmıştır (p 0.05). Sonuç: Tüm bu veriler, piRNA'ların bazılarının hepatoselüler karsinomda özel ekspresyon paternlerine sahip olabileceğini ve bu ekspresyon paternlerinin, uygulanan doğal bileşikler tarafından düzenlenebileceğini göstermektedir. Hepatoselüler karsinomda tek tek etkili olduğu gözlenen maddelerin, beklentilerin aksine farklı piRNA ekspresyon değişikliklerine neden olabileceğini savunmaktayız.

How do the effective therapeutics for hepatocellular carcinoma treatment change PIWI Interacting RNA expressions?

Aim: PIWI interacting RNAs (piRNAs) are novel members of small non-coding RNAs that cannot produce proteins but are effective on transcription and posttranscriptional mechanisms of cells. Nowadays, the application of both natural compounds and vitamins is essential for treatment of cancer cells instead of chemical compounds. In this study, we aimed to detect possible expression changes of piRNAs in order to compare 4- Hydroxycoumarin to the active form of vitamin D (1.25-Dihydroxyvitamin D) in hepatocellular carcinoma. Methods: According to our previous study, HePG2 cells were treated with 4- Hydroxycoumarin, 1.25-Dihydroxyvitamin D and drug form of vitamin D at the optimal time and concentration. After treatment, the total RNA was isolated and expressions of piR-Hep-1 and piR-651 were determined by using Real Time Polymerase Chain Reactions. Results: According to our obtained data, statistically significant upregulation of piR-651 expression was observed in 4-Hydroxycoumarin-treated HePG2 cells compared to control (p0.05). In contrast, 1.25-dihydroxyvitamin treatment downregulated the expression of piR-Hep-1 statistically significant in HePG2 cells (p0.05). Conclusion: Our results indicated that some of the piRNAs might have special expression patterns in hepatocellular carcinoma and these expression patterns can be regulated by treated natural compounds. We suggest that substances that are observed to be effective in hepatocellular carcinoma individually may result in different piRNA expression changes contrary to the expectations

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