miR-29a-5p modulates ferroptosis by targeting ferritin heavy chain FTH1 in prostate cancer
Guang Yang, Qi Pan, Yang Lu, Junlong Zhu, Xin Gou
Abstract
Ferroptosis is a kind of regulatory necrosis caused by phospholipid iron-dependent peroxidation. MiRNAs are known to play key roles in diverse biological functions. However, the molecular basis of miRNA-mediated ferroptosis in prostate cancer has not been fully stated. Here, with TCGA prostate cancer miRNA-seq data, we utilized Multivariate Cox regression analysis to prioritize potential miRNA and validated it in vitro and in vivo. We identified miR-29a-5p by TCGA prostate cancer miRNA-seq dataset. And we confirmed the expression of miR-29a-5p in prostate cancer cell lines. MiR-29a-5p knockdown reduced proliferation in PC-3 and LNCaP cells while increased Fe2+ and malondialdehyde (MDA) levels, the opposite phenomenon was observed with miR-29a-5p overexpression. Luciferase reporter assay showed an interaction between miR-29a-5p and Nrf2 downstream gene FTH1, subsequent rescue experiments also indirectly proved their direct effect. Finally, suppression of miR-29a-5p effectively inhibited tumor growth in vivo. These findings proved that the important role of miR-29a-5p in prostate cancer ferroptosis.