# SLC25A37 as a novel therapeutic target for benign prostatic hyperplasia: integrative analyses of single-cell RNA sequencing and genome-wide association studies

## TL;DR

This study identifies SLC25A37 as a new potential treatment target for benign prostatic hyperplasia using RNA sequencing and genetic analysis.

## Contribution

The study integrates single-cell RNA sequencing and genome-wide association data to discover SLC25A37 as a novel causal gene for BPH.

## Key findings

- BPH patients have increased myeloid cells and 85 monocyte-specific differentially expressed genes.
- SLC25A37 is causally linked to BPH through multiple genetic analyses and is involved in proliferation pathways.
- Ferriheme chloride and catechol are potential drugs targeting SLC25A37, with in vitro validation of gene expression.

## Abstract

To identify causal genes for benign prostatic hyperplasia (BPH) based on single-cell RNA sequencing (scRNA-seq) and genome-wide association studies.

We explored scRNA-seq datasets to identify the differentially expressed genes (DEGs) in BPH patients vs. healthy controls. Mendelian randomization (MR) was conducted to investigate the causal relationships between the identified DEGs and BPH. Bayesian colocalization and reverse MR were performed to consolidate the MR findings. Potential therapeutic drugs targeting causal genes were explored via molecular docking. The results of bioinformatics analyses were validated through experiments including flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence staining.

BPH patients showed an increased proportion of myeloid cells in the prostate transition zone, with 85 classical monocyte-specific DEGs. Among these, SLC25A37 was causally associated with BPH based on MR, Bayesian colocalization, and reverse MR analyses. Functional analyses indicated its involvement in proliferation-related signaling pathways in classical monocytes. Ferriheme chloride and catechol were identified as potential drugs targeting SLC25A37. In vitro study confirmed increased expression levels of SLC25A37 and myeloid cells in BPH tissues.

Our integrative analyses revealed SLC25A37 as a novel causal gene in BPH pathogenesis, unveiling potential therapeutic strategies for BPH treatment.