Identification of androgen response‐related lncRNAs in prostate cancer

Author:

Karthikeyan Santhosh Kumar1,Xu Nuo2,Ferguson 3 James E.3,Rais‐Bahrami Soroush34,Qin Zhaohui S.5,Manne Upender14,Netto George J.14,S. Chandrashekar Darshan1,Varambally Sooryanarayana146ORCID

Affiliation:

1. Department of Pathology University of Alabama at Birmingham Birmingham Alabama USA

2. Collat School of Business University of Alabama at Birmingham Birmingham Alabama USA

3. Department of Urology University of Alabama at Birmingham Birmingham Alabama USA

4. O'Neal Comprehensive Cancer Center University of Alabama at Birmingham Birmingham Alabama USA

5. Department of Biostatistics and Bioinformatics Emory University Atlanta Georgia USA

6. Informatics Institute University of Alabama at Birmingham Birmingham Alabama USA

Abstract

AbstractBackgroundLong noncoding RNAs (lncRNAs) are RNA molecules with over 200 nucleotides that do not code for proteins, but are known to be widely expressed and have key roles in gene regulation and cellular functions. They are also found to be involved in the onset and development of various cancers, including prostate cancer (PCa). Since PCa are commonly driven by androgen regulated signaling, mainly stimulated pathways, identification and determining the influence of lncRNAs in androgen response is useful and necessary. LncRNAs regulated by the androgen receptor (AR) can serve as potential biomarkers for PCa. In the present study, gene expression data analysis were performed to distinguish lncRNAs related to the androgen response pathway.Methods and ResultsWe used publicly available RNA‐sequencing and ChIP‐seq data to identify lncRNAs that are associated with the androgen response pathway. Using Universal Correlation Coefficient (UCC) and Pearson Correlation Coefficient (PCC) analyses, we found 15 lncRNAs that have (a) highly correlated expression with androgen response genes in PCa and are (b) differentially expressed in the setting of treatment with an androgen agonist as well as antagonist compared to controls. Using publicly available ChIP‐seq data, we investigated the role of androgen/AR axis in regulating expression of these lncRNAs. We observed AR binding in the promoter regions of 5 lncRNAs (MIR99AHG, DUBR, DRAIC, PVT1, and COLCA1), showing the direct influence of AR on their expression and highlighting their association with the androgen response pathway.ConclusionBy utilizing publicly available multiomics data and by employing in silico methods, we identified five candidate lncRNAs that are involved in the androgen response pathway. These lncRNAs should be investigated as potential biomarkers for PCa.

Funder

U.S. Department of Defense

Publisher

Wiley

Subject

Urology,Oncology

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