Androgen receptor deficiency-induced TUG1 in suppressing ferroptosis to promote benign prostatic hyperplasia through the miR-188-3p/GPX4 signal pathway

• DOI: 10.1016/j.redox.2024.103298
• Publication Date: 2024-08-02T11:16:41Z
• Authors: Ming Zhan; Huan Xu; Guopeng Yu; Qi Chen; Ruifeng Yang; Yanbo Chen; Jianchao Ge; Zhong Wang; Ruimeng Yang; Bin Xu
• Keywords: GPX4

Benign prostatic hyperplasia (BPH), characterized by the non-malignant enlargement of prostate, exhibits a pronounced association with inflammation resulting from androgen receptor (AR) deficiency. Ferroptosis, cell death mechanism triggered iron-dependent lipid peroxidation and closely linked to inflammation, has yet be fully understood in context BPH. Using RNA sequencing, we observed significant elevation taurine-upregulated gene 1 (TUG1) long noncoding (lncRNA) BPH tissues compared normal prostate tissue. High levels TUG1 exhibited discernible correlation both volume extent inflammatory infiltration patients. The suppression not only led reduction size but also ameliorated AR-deficiency-induced hyperplasia. Mechanistically, decrease AR luminal cells prompted macrophage aggregation release IL-1β, subsequently fostering transcription via MYC. Induced TUG1, through competitive binding miR-188-3p, facilitated expression GPX4, thereby diminishing intracellular ROS impeding ferroptosis cells. Notably, inducer JKE-1674 alleviated inflammation-induced vivo. Together, these findings suggest that deficiency crucially inhibits ferroptosis, promoting TUG1/miR-188-3p/GPX4 signaling axis, making induction promising therapeutic strategy for patients