LncRNA <i>PCAT1</i> and its genetic variant rs1902432 are associated with prostate cancer risk

Abstract

Emerging evidence has showed that lncRNAs and trait-associated loci in lncRNAs play a crucial role in the progression of cancer including prostate cancer (PCa).This study aimed to investigate the molecular mechanisms of lncRNA <i>PCAT1</i> involved in PCa development and its genetic variant associated with PCa risk. We applied cell proliferation and apoptosis assays to assess the effect of <i>PCAT1</i> on PCa cell phenotypes. In addition, the genome-wide profiling of gene expression was assessed from three pairs of DU145 cells transfected with <i>PCAT1</i> overexpression vector or negative control (NC) vector. Furthermore, a case-control study was conducted to explore the associations of four tagging single nucleotide polymorphisms (tagSNPs) and PCa risk in 850 PCa cases and 860 cancer-free controls. Our results showed that lncRNA <i>PCAT1</i> promoted cell proliferation and inhibited cell apoptosis. Ingenuity pathway analysis (IPA) indicated that dysregulated mRNAs induced by overexpression of <i>PCAT1</i> were primarily enriched in androgen-independent prostate tumor term and implicated in the disease and functions networks, such as cell death and survival, cell proliferation and gene expression. Besides, rs1902432 in <i>PCAT1</i> was significantly associated with increased risk of PCa (Additive model: OR = 1.19, <i>P</i> = 0.014; Co-dominant model: CC <i>vs.</i> TT, OR = 1.45, <i>P</i> =0.012; Recessive model: CC <i>vs.</i> TT/CT, OR= 1.34, <i>P</i> = 0.027). This study suggests that <i>PCAT1</i> may act as an oncogene through promoting cell proliferation and suppressing cell apoptosis in PCa development, and genetic variant in <i>PCAT1</i> contributes to the susceptibility to PCa.