Yang Guang, Pan Qi, Lu Yang, Zhu Junlong, Gou Xin
Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
Department of Dermatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, PR China.
Biochem Biophys Res Commun. 2023 Apr 16;652:6-13. doi: 10.1016/j.bbrc.2023.02.030. Epub 2023 Feb 16.
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 Fe 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.
铁死亡是一种由磷脂铁依赖性过氧化作用引起的调节性坏死。已知微小RNA（miRNA）在多种生物学功能中发挥关键作用。然而，miRNA介导的前列腺癌铁死亡的分子基础尚未完全阐明。在此，利用TCGA前列腺癌miRNA测序数据，我们采用多变量Cox回归分析对潜在的miRNA进行优先级排序，并在体外和体内进行了验证。我们通过TCGA前列腺癌miRNA测序数据集鉴定出miR-29a-5p。并且我们证实了miR-29a-5p在前列腺癌细胞系中的表达。敲低miR-29a-5p可降低PC-3和LNCaP细胞的增殖，同时提高铁和丙二醛（MDA）水平，而miR-29a-5p过表达则观察到相反的现象。荧光素酶报告基因检测显示miR-29a-5p与Nrf2下游基因FTH1之间存在相互作用，随后的拯救实验也间接证明了它们的直接作用。最后，抑制miR-29a-5p可有效抑制体内肿瘤生长。这些发现证明了miR-29a-5p在前列腺癌铁死亡中的重要作用。
