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.