羟氯喹可调控前列腺癌细胞中的 m6A RNA 甲基化

Sevinc Yanar, Merve Gülsen BAL ALBAYRAK
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引用次数: 0

摘要

前列腺癌是全球男性发病率第二高的癌症。N6-甲基腺苷(m6A)修饰的作用是前列腺癌研究中不断发展的课题之一。羟基氯喹(HCQ)是一种自噬抑制剂,在增强前列腺癌患者对化疗的反应方面很有前景。自噬与 m6A 之间的相互作用是一个新兴的研究领域。然而,m6A修饰与HCQ之间的关系仍不清楚。本研究旨在探讨 HCQ 对前列腺癌 m6A 甲基化调控的影响。首先评估了 HCQ 对 LNCaP 和 PC3 细胞的细胞毒性作用。计算了每种细胞的 IC50 值。最后,使用 m6A RNA 甲基化定量试剂盒测定 HCQ 处理和未处理细胞中的 m6A 水平。HCQ 对细胞存活率的降低具有明显的剂量和时间依赖性。经 HCQ 处理后,m6A 水平出现了统计学意义上的显著下降:在 PC3 细胞中从 0.050±0.001% 降至 0.013±0.02%,在 LNCaP 细胞中从 0.039±0.001% 降至 0.016±0.01%。该研究首次揭示了HCQ对前列腺癌m6A甲基化的影响。自噬抑制剂HCQ对m6A修饰的影响为其潜在的作用机制引入了一个新的维度。
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Hidroksiklorokin Prostat Kanseri Hücrelerinde m6A RNA Metilasyonunu Düzenler
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.
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