Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers

Abstract

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.