Systematic Evaluation of the Effects of Genetic Variants on PIWI-interacting RNA Expression Across 33 Cancer Types

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2020 Dec 17

PMID 33330918

Citations 20

Authors

Junyi Xin

Mulong Du

Xia Jiang

Yanling Wu

Shuai Ben

Rui Zheng

Haiyan Chu

Shuwei Li

Zhengdong Zhang

Meilin Wang

Affiliations

Soon will be listed here.

Abstract

PIWI-interacting RNAs (piRNAs) are an emerging class of non-coding RNAs involved in tumorigenesis. Expression quantitative trait locus (eQTL) analysis has been demonstrated to help reveal the genetic mechanism of single nucleotide polymorphisms (SNPs) in cancer etiology. However, there are no databases that have been constructed to provide an eQTL analysis between SNPs and piRNA expression. In this study, we collected genotyping and piRNA expression data for 10 997 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Using linear regression cis-eQTL analysis with adjustment of appropriate covariates, we identified millions of SNP-piRNA pairs in tumor (76 924 831) and normal (24 431 061) tissues. Further, we performed differential expression and survival analyses, and linked the eQTLs to genome-wide association study (GWAS) data to comprehensively decipher the functional roles of identified cis-piRNA eQTLs. Finally, we developed a user-friendly database, piRNA-eQTL (http://njmu-edu.cn:3838/piRNA-eQTL/), to help users query, browse and download corresponding eQTL results. In summary, piRNA-eQTL could serve as an important resource to assist the research community in understanding the roles of genetic variants and piRNAs in the development of cancers.

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References

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

Ongen H, Andersen C, Bramsen J, Oster B, Rasmussen M, Ferreira P . Putative cis-regulatory drivers in colorectal cancer. Nature. 2014; 512(7512):87-90. DOI: 10.1038/nature13602. View

Mai D, Ding P, Tan L, Zhang J, Pan Z, Bai R . PIWI-interacting RNA-54265 is oncogenic and a potential therapeutic target in colorectal adenocarcinoma. Theranostics. 2018; 8(19):5213-5230. PMC: 6276099. DOI: 10.7150/thno.28001. View

Calabrese C, Davidson N, Demircioglu D, Fonseca N, He Y, Kahles A . Genomic basis for RNA alterations in cancer. Nature. 2020; 578(7793):129-136. PMC: 7054216. DOI: 10.1038/s41586-020-1970-0. View

Gilad Y, Rifkin S, Pritchard J . Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet. 2008; 24(8):408-15. PMC: 2583071. DOI: 10.1016/j.tig.2008.06.001. View

Price A, Patterson N, Plenge R, Weinblatt M, Shadick N, Reich D . Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006; 38(8):904-9. DOI: 10.1038/ng1847. View

Girard A, Sachidanandam R, Hannon G, Carmell M . A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature. 2006; 442(7099):199-202. DOI: 10.1038/nature04917. View

Quinlan A, Hall I . BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010; 26(6):841-2. PMC: 2832824. DOI: 10.1093/bioinformatics/btq033. View

Gong J, Mei S, Liu C, Xiang Y, Ye Y, Zhang Z . PancanQTL: systematic identification of cis-eQTLs and trans-eQTLs in 33 cancer types. Nucleic Acids Res. 2017; 46(D1):D971-D976. PMC: 5753226. DOI: 10.1093/nar/gkx861. View

10.

Yan Z, Hu H, Jiang X, Maierhofer V, Neb E, He L . Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res. 2011; 39(15):6596-607. PMC: 3159465. DOI: 10.1093/nar/gkr298. View

11.

Li J, Xue Y, Amin M, Yang Y, Yang J, Zhang W . ncRNA-eQTL: a database to systematically evaluate the effects of SNPs on non-coding RNA expression across cancer types. Nucleic Acids Res. 2019; 48(D1):D956-D963. PMC: 6943077. DOI: 10.1093/nar/gkz711. View

12.

Gong J, Wan H, Mei S, Ruan H, Zhang Z, Liu C . Pancan-meQTL: a database to systematically evaluate the effects of genetic variants on methylation in human cancer. Nucleic Acids Res. 2018; 47(D1):D1066-D1072. PMC: 6323988. DOI: 10.1093/nar/gky814. View

13.

Liu Y, Dou M, Song X, Dong Y, Liu S, Liu H . The emerging role of the piRNA/piwi complex in cancer. Mol Cancer. 2019; 18(1):123. PMC: 6688334. DOI: 10.1186/s12943-019-1052-9. View

14.

Visscher P, Wray N, Zhang Q, Sklar P, McCarthy M, Brown M . 10 Years of GWAS Discovery: Biology, Function, and Translation. Am J Hum Genet. 2017; 101(1):5-22. PMC: 5501872. DOI: 10.1016/j.ajhg.2017.06.005. View

15.

Wang J, Zhang P, Lu Y, Li Y, Zheng Y, Kan Y . piRBase: a comprehensive database of piRNA sequences. Nucleic Acids Res. 2018; 47(D1):D175-D180. PMC: 6323959. DOI: 10.1093/nar/gky1043. View

16.

Tian J, Wang Z, Mei S, Yang N, Yang Y, Ke J . CancerSplicingQTL: a database for genome-wide identification of splicing QTLs in human cancer. Nucleic Acids Res. 2018; 47(D1):D909-D916. PMC: 6324030. DOI: 10.1093/nar/gky954. View

17.

Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis G . Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet. 2012; 44(8):955-9. PMC: 3696580. DOI: 10.1038/ng.2354. View

18.

Li L, Fridley B, Kalari K, Niu N, Jenkins G, Batzler A . Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines. BMC Genomics. 2014; 15:93. PMC: 3930546. DOI: 10.1186/1471-2164-15-93. View

19.

Shabalin A . Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics. 2012; 28(10):1353-8. PMC: 3348564. DOI: 10.1093/bioinformatics/bts163. View

20.

Weinhold N, Jacobsen A, Schultz N, Sander C, Lee W . Genome-wide analysis of noncoding regulatory mutations in cancer. Nat Genet. 2014; 46(11):1160-5. PMC: 4217527. DOI: 10.1038/ng.3101. View