J Cancer 2018; 9(8):1414-1420. doi:10.7150/jca.23685

Research Paper

LncRNA PCAT1 and its genetic variant rs1902432 are associated with prostate cancer risk

Qinbo Yuan1,2,3,4,†, Haiyan Chu1,2,†, Yuqiu Ge1,2,†, Gaoxiang Ma1,2, Mulong Du1,2, Meilin Wang1,2, Zhengdong Zhang1,2,✉, Wei Zhang4,✉

1. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
2. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
3. Department of Urology, Huaiyin Hospital of Huai'an City, Huai'an, China
4. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
These authors contributed equally to this work.

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Yuan Q, Chu H, Ge Y, Ma G, Du M, Wang M, Zhang Z, Zhang W. LncRNA PCAT1 and its genetic variant rs1902432 are associated with prostate cancer risk. J Cancer 2018; 9(8):1414-1420. doi:10.7150/jca.23685. Available from http://www.jcancer.org/v09p1414.htm

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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 PCAT1 involved in PCa development and its genetic variant associated with PCa risk. We applied cell proliferation and apoptosis assays to assess the effect of PCAT1 on PCa cell phenotypes. In addition, the genome-wide profiling of gene expression was assessed from three pairs of DU145 cells transfected with PCAT1 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 PCAT1 promoted cell proliferation and inhibited cell apoptosis. Ingenuity pathway analysis (IPA) indicated that dysregulated mRNAs induced by overexpression of PCAT1 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 PCAT1 was significantly associated with increased risk of PCa (Additive model: OR = 1.19, P = 0.014; Co-dominant model: CC vs. TT, OR = 1.45, P =0.012; Recessive model: CC vs. TT/CT, OR= 1.34, P = 0.027). This study suggests that PCAT1 may act as an oncogene through promoting cell proliferation and suppressing cell apoptosis in PCa development, and genetic variant in PCAT1 contributes to the susceptibility to PCa.

Keywords: PCAT1, lncRNA, genetic variant, prostate cancer, molecular epidemiology