Decoding ceRNA regulatory network and autophagy-related genes in benign prostatic hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) is a common disease among aging males. We obtained BPH transcriptional signatures by high-throughput RNA sequencing analysis. Accordingly, we determined the differentially expressed RNAs (DERNAs) between BPH tissues and normal prostate tissues. WebGestalt and R package (clusterprofiler) was used to enrichment analysis. Clinical correlations were analyzed using Spearman's coefficient. TargetScan, ENCORI, miRNet, and miRDB databases were used to predict targets' relationships in ceRNA networks. Immunofluorescence staining and qRT-PCR analyses were performed to validate the findings. Microarray analysis of the datasets showed 369 DElncRNAs, 122 DEpseudogenes, 6 DEmiRNAs and 1358 DEmRNAs. DEmRNAs were particularly enriched in the autophagy-related pathways. Following the screening of DEmRNAs and autophagy-related genes (ARGs), 50 DEARGs were selected. MCODE analysis on Cytoscape was performed for the 50 DEARGs, and 3 hub genes (ATF4, XBP1, and PPP1R15A) were obtained. Spearman's correlation analysis showed that the mRNA expression of XBP1 correlated positively with age, total score, and storage score, but negatively with the maximum flow rate. Subsequently, the pseudogene/lncRNA- hsa-miR-222-3p-XBP1 pathway was identified. Our findings elucidate that the pseudogene/lncRNA-hsa-miR-222-3p-XBP1 pathway may play a regulatory role in the occurrence of BPH through autophagy.

Keywords: BPH; Differentially expressed autophagy-related genes(DEARGs); ceRNA.