Hydroxychloroquine Modulates m6A RNA Methylation in Prostate Cancer Cells

Sevinc Yanar; Merve Gülsen Bal Albayrak

doi:10.17776/csj.1307100

EN TR

Hydroxychloroquine Modulates m6A RNA Methylation in Prostate Cancer Cells

Abstract

Prostate cancer ranks as the second most prevalent cancer in men globally. One of the evolving subjects of investigation in prostate cancer is the role of N6-methyladenosine (m6A) modifications. Hydroxychloroquine (HCQ), an autophagy inhibitor, was shown to be promising in enhancing the response to chemotherapy in prostate cancer. The interplay between autophagy and m6A is an emerging area of research. However, the relationship between m6A modifications and HCQ remains unclear. The objective of this study was to examine the effect of HCQ on the regulation of m6A methylation in prostate cancer. Initially, the cytotoxic effect of HCQ on LNCaP and PC3 cells was evaluated. The IC50 values for each cell were calculated. Finally, m6A levels in HCQ-treated and untreated cells were determined using m6A RNA methylation quantification kit. HCQ showed a significant dose- and time-dependent reduction in cell viability. Following HCQ treatment, a statistically significant decrease in m6A levels was observed: from 0.050±0.001% to 0.013±0.02% in PC3 cells and from 0.039±0.001% to 0.016±0.01% in LNCaP cells. The study unveils for the first time that HCQ affects m6A methylation in prostate cancer. The impact of autophagy inhibitor HCQ on m6A modifications introduces a novel dimension to its potential mechanisms of action.

Keywords

Hidroksiklorokin Prostat Kanseri Hücrelerinde m6A RNA Metilasyonunu Düzenler

Öz

N6-metiladenozin (m6A) modifikasyonlarının rolü prostat kanseri araştırmalarında gelişmekte olan bir alandır ve bu modifikasyonlar kanser dâhil çeşitli hücresel süreçlerle ilişkilendirilmiştir. Otofaji inhibitörü olan hidroksiklorokin (HCQ), prostat kanserinde kemoterapiye yanıtı artırmada umut verici sonuçlar göstermiştir. Ancak, m6A modifikasyonları ile HCQ arasındaki ilişki prostat kanserinde henüz net değildir. Bu nedenle, bu çalışmanın amacı HCQ'nun prostat kanseri hücrelerinde m6A metilasyonunun düzenlenmesine olan etkisini incelemektir. İlk olarak, HCQ'nun LNCaP, PC3 ve PNT1A hücreleri üzerindeki sitotoksik etkisi değerlendirildi. Ardından, her hücre hattı için yarı maksimal inhibisyon konsantrasyonu değerleri hesaplandı. Son olarak, HCQ ile muamele edilen ve edilmeyen hücrelerdeki m6A seviyeleri ticari m6A RNA metilasyon kantifikasyon kiti kullanılarak belirlendi. HCQ, LNCaP ve PC3 hücrelerinde doza ve zamana bağlı olarak hücre canlılığında belirgin bir azalmaya neden oldu, ancak normal prostat hücreleri olan PNT1A'da toksisiteye yol açmadı. HCQ tedavisi sonrasında hem LNCaP hem de PC3 hücrelerinde m6A seviyesinde istatistiksel olarak anlamlı bir azalma gözlendi. Bu çalışma, HCQ'nun prostat kanseri hücrelerinde m6A metilasyonunu etkilediğini ilk kez ortaya koymaktadır. Otofaji ile m6A arasındaki etkileşim, gelişmekte olan bir araştırma alanıdır ve otofaji inhibitörü HCQ'nun m6A modifikasyonları üzerindeki etkisi, potansiyel etki mekanizmalarına yeni bir boyut kazandırmaktadır.

Anahtar Kelimeler

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Details

Primary Language

English

Subjects

Structural Biology

Journal Section

Research Article

Authors

Sevinc Yanar ^*
0000-0002-6438-7385
Türkiye

Merve Gülsen Bal Albayrak
0000-0003-2444-4258
Türkiye

Publication Date

December 28, 2023

Submission Date

May 30, 2023

Acceptance Date

November 21, 2023

Published in Issue

Year 2023 Volume: 44 Number: 4

DOI

https://doi.org/10.17776/csj.1307100

IZ

https://izlik.org/JA34RF43SH

Cite

RIS / Bibtex

APA

Yanar, S., & Bal Albayrak, M. G. (2023). Hydroxychloroquine Modulates m6A RNA Methylation in Prostate Cancer Cells. Cumhuriyet Science Journal, 44(4), 629-634. https://doi.org/10.17776/csj.1307100

Cited By

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OMICS: A Journal of Integrative Biology

https://doi.org/10.1089/omi.2024.0061