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  • ISSN 1674-8301
  • CN 32-1810/R
Volume 37 Issue 6
Nov.  2023
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Ting Liu, Jingjing Gu, Chuning Li, Mengfan Guo, Lin Yuan, Qiang Lv, Chao Qin, Mulong Du, Haiyan Chu, Hanting Liu, Zhengdong Zhang. Alternative polyadenylation-related genetic variants contribute to bladder cancer risk[J]. The Journal of Biomedical Research, 2023, 37(6): 405-417. DOI: 10.7555/JBR.37.20230063
Citation: Ting Liu, Jingjing Gu, Chuning Li, Mengfan Guo, Lin Yuan, Qiang Lv, Chao Qin, Mulong Du, Haiyan Chu, Hanting Liu, Zhengdong Zhang. Alternative polyadenylation-related genetic variants contribute to bladder cancer risk[J]. The Journal of Biomedical Research, 2023, 37(6): 405-417. DOI: 10.7555/JBR.37.20230063
shu

Alternative polyadenylation-related genetic variants contribute to bladder cancer risk

  • 1.

    Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China

  • 2.

    Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China

  • 3.

    Department of Urology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, China

  • 4.

    Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

More Information
  • Corresponding author:

    Hanting Liu and Zhengdong Zhang, Department of Environmental Genomics, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China. Tels: +86-25-8686-8423/+86-25-8686-8499. E-mails: hantingliu@njmu.edu.cn (Liu) and drzdzhang@njmu.edu.cn (Zhang)

  • △These authors contributed equally to this work.

  • Received Date: March 19, 2023
  • Revised Date: May 25, 2023
  • Accepted Date: May 27, 2023
  • Available Online: November 14, 2023
  • Published Date: November 14, 2023
    Graphical Abstract
    • Abstract

  • Aberrant alternative polyadenylation (APA) events play an important role in cancers, but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer. Previous genome-wide association study performed APA quantitative trait loci (apaQTL) analyses in bladder cancer, and identified 17 955 single nucleotide polymorphisms (SNPs). We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways, high mutational burden, and immune infiltration. Association analysis showed that apaQTL-associated SNPs rs34402449 C>A, rs2683524 C>T, and rs11540872 C>G were significantly associated with susceptibility to bladder cancer (rs34402449: OR = 1.355, 95% confidence interval [CI]: 1.159–1.583, P = 1.33 × 10−4; rs2683524: OR = 1.378, 95% CI: 1.164–1.632, P = 2.03 × 10−4; rs11540872: OR = 1.472, 95% CI: 1.193–1.815, P = 3.06 × 10−4). Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer (Ptrend = 2.87 × 10−12). We found that PRR13, being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines, was more highly expressed in bladder cancer tissues than in adjacent normal tissues. Moreover, the rs2683524 T allele was correlated with shorter 3′ untranslated regions of PRR13 and increased PRR13 expression levels. Collectively, our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.

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  • The current study was supported by the National Natural Science Foundation of China (Grant Nos. 82130096 and 82373537), Collaborative Innovation Center for Cancer Personalized Medicine and Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

    The authors would like to acknowledge helpful discussions and input from Professor Meilin Wang of Nanjing Medical University. The authors would like to thank Gong Jing's team at Huazhong Agricultural University for providing relevant data.

    CLC number: R737.14, Document code: A

    The authors reported no conflict of interests.

    • References (35)
  • [1]
    Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209–249. doi: 10.3322/caac.21660
    [2]
    Li H, Zheng R, Du L, et al. Bladder cancer incidence, mortality and temporal trends in China[J]. Chin J Oncol (in Chinese), 2021, 43(3): 293–298. doi: 10.3760/cma.j.cn112152-20200421-00362
    [3]
    Li H, Duymich CE, Weisenberger DJ, et al. Genetic and epigenetic alterations in bladder cancer[J]. Int Neurourol J, 2016, 20(S2): S84–S94. doi: 10.5213/inj.1632752.376
    [4]
    Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity[J]. Nat Rev Cancer, 2015, 15(1): 25–41. doi: 10.1038/nrc3817
    [5]
    Wang M, Li Z, Chu H, et al. Genome-wide association study of bladder cancer in a chinese cohort reveals a new susceptibility locus at 5q12.3[J]. Cancer Res, 2016, 76(11): 3277–3284. doi: 10.1158/0008-5472.CAN-15-2564
    [6]
    Zheng R, Du M, Ge Y, et al. Identification of low-frequency variants of UGT1A3 associated with bladder cancer risk by next-generation sequencing[J]. Oncogene, 2021, 40(13): 2382–2394. doi: 10.1038/s41388-021-01672-1
    [7]
    Liu H, Gu J, Jin Y, et al. Genetic variants in N6-methyladenosine are associated with bladder cancer risk in the Chinese population[J]. Arch Toxicol, 2021, 95(1): 299–309. doi: 10.1007/s00204-020-02911-2
    [8]
    Nachtergaele S, He C. Chemical modifications in the life of an mRNA transcript[J]. Annu Rev Genet, 2018, 52: 349–372. doi: 10.1146/annurev-genet-120417-031522
    [9]
    Kaida D. The reciprocal regulation between splicing and 3'-end processing[J]. WIREs RNA, 2016, 7(4): 499–511. doi: 10.1002/wrna.1348
    [10]
    Elkon R, Ugalde AP, Agami R. Alternative cleavage and polyadenylation: extent, regulation and function[J]. Nat Rev Genet, 2013, 14(7): 496–506. doi: 10.1038/nrg3482
    [11]
    Hoque M, Ji Z, Zheng D, et al. Analysis of alternative cleavage and polyadenylation by 3' region extraction and deep sequencing[J]. Nat Methods, 2013, 10(2): 133–139. doi: 10.1038/nmeth.2288
    [12]
    Ren F, Zhang N, Zhang L, et al. Alternative Polyadenylation: a new frontier in post transcriptional regulation[J]. Biomark Res, 2020, 8(1): 67. doi: 10.1186/s40364-020-00249-6
    [13]
    Tian B, Manley JL. Alternative polyadenylation of mRNA precursors[J]. Nat Rev Mol Cell Biol, 2017, 18(1): 18–30. doi: 10.1038/nrm.2016.116
    [14]
    Zhou R, Xiao X, He P, et al. SCAPE: a mixture model revealing single-cell polyadenylation diversity and cellular dynamics during cell differentiation and reprogramming[J]. Nucleic Acids Res, 2022, 50(11): e66. doi: 10.1093/nar/gkac167
    [15]
    Gruber AJ, Zavolan M. Alternative cleavage and polyadenylation in health and disease[J]. Nat Rev Genet, 2019, 20(10): 599–614. doi: 10.1038/s41576-019-0145-z
    [16]
    Joehanes R, Zhang X, Huan T, et al. Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies[J]. Genome Biol, 2017, 18(1): 16. doi: 10.1186/s13059-016-1142-6
    [17]
    Patro CPK, Nousome D, The Glioma International Case Control Study (GICC), et al. Meta-analyses of splicing and expression quantitative trait loci identified susceptibility genes of glioma[J]. Front Genet, 2021, 12: 609657. doi: 10.3389/fgene.2021.609657
    [18]
    Li L, Huang KL, Gao Y, et al. An atlas of alternative polyadenylation quantitative trait loci contributing to complex trait and disease heritability[J]. Nat Genet, 2021, 53(7): 994–1005. doi: 10.1038/s41588-021-00864-5
    [19]
    Yang Y, Zhang Q, Miao Y, et al. SNP2APA: a database for evaluating effects of genetic variants on alternative polyadenylation in human cancers[J]. Nucleic Acids Res, 2020, 48(D1): D226–D232. doi: 10.1093/nar/gkz793
    [20]
    Xia Z, Donehower LA, Cooper TA, et al. Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types[J]. Nat Commun, 2014, 5: 5274. doi: 10.1038/ncomms6274
    [21]
    Thorsson V, Gibbs DL, Brown SD, et al. The immune landscape of cancer[J]. Immunity, 2018, 48(4): 812–830.e14. doi: 10.1016/j.immuni.2018.03.023
    [22]
    Ma L, Zhang D, Huang Z, et al. Functional variants of RPS6KB1 and PIK3R1 in the autophagy pathway genes and risk of bladder cancer[J]. Arch Toxicol, 2022, 96(1): 367–375. doi: 10.1007/s00204-021-03173-2
    [23]
    Xin J, Du M, Gu D, et al. Combinations of single nucleotide polymorphisms identified in genome-wide association studies determine risk for colorectal cancer[J]. Int J Cancer, 2019, 145(10): 2661–2669. doi: 10.1002/ijc.32267
    [24]
    Gillani R, Seong BKA, Crowdis J, et al. Gene fusions create partner and collateral dependencies essential to cancer cell survival[J]. Cancer Res, 2021, 81(15): 3971–3984. doi: 10.1158/0008-5472.CAN-21-0791
    [25]
    Maraver A, Fernandez-Marcos PJ, Cash TP, et al. NOTCH pathway inactivation promotes bladder cancer progression[J]. J Clin Invest, 2015, 125(2): 824–830. doi: 10.1172/JCI78185
    [26]
    Wacholder S, Chanock S, Garcia-Closas M, et al. Assessing the probability that a positive report is false: an approach for molecular epidemiology studies[J]. J Natl Cancer Inst, 2004, 96(6): 434–442. doi: 10.1093/jnci/djh075
    [27]
    Court CM, Hou S, Liu L, et al. Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells[J]. npj Precis Oncol, 2020, 4: 16. doi: 10.1038/s41698-020-0123-0
    [28]
    Lakshmi Narendra B, Eshvendar Reddy K, Shantikumar S, et al. Immune system: a double-edged sword in cancer[J]. Inflamm Res, 2013, 62(9): 823–834. doi: 10.1007/s00011-013-0645-9
    [29]
    Yang H, Che D, Gu Y, et al. Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma[J]. Front Genet, 2022, 13: 940306. doi: 10.3389/fgene.2022.940306
    [30]
    Tian J, Chen C, Rao M, et al. Aberrant RNA splicing is a primary link between genetic variation and pancreatic cancer risk[J]. Cancer Res, 2022, 82(11): 2084–2096. doi: 10.1158/0008-5472.CAN-21-4367
    [31]
    Sun Y, Zhang X, Yang S, et al. Preparation of antibodies against TXR1 and construction of a new DNA tumor vaccine[J]. Int Immunopharmacol, 2022, 103: 108505. doi: 10.1016/j.intimp.2021.108505
    [32]
    Lih CJ, Wei W, Cohen SN. Txr1: a transcriptional regulator of thrombospondin-1 that modulates cellular sensitivity to taxanes[J]. Genes Dev, 2006, 20(15): 2082–2095. doi: 10.1101/gad.1441306
    [33]
    van Amerongen R, Berns A. TXR1-mediated thrombospondin repression: a novel mechanism of resistance to taxanes?[J]. Genes Dev, 2006, 20(15): 1975–1981. doi: 10.1101/gad.1460806
    [34]
    Papadaki C, Mavroudis D, Trypaki M, et al. Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen[J]. Clin Cancer Res, 2009, 15(11): 3827–3833. doi: 10.1158/1078-0432.CCR-08-3027
    [35]
    Cumberbatch MG, Rota M, Catto JWF, et al. The role of tobacco smoke in bladder and kidney carcinogenesis: a comparison of exposures and meta-analysis of incidence and mortality risks[J]. Eur Urol, 2016, 70(3): 458–466. doi: 10.1016/j.eururo.2015.06.042
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    2. Elshahawy IS, Mohammed ES, Mawas AS, et al. First microscopic, pathological, epidemiological, and molecular investigation of Leucocytozoon (Apicomplexa: Haemosporida) parasites in Egyptian pigeons. Front Vet Sci, 2024, 11: 1434627. DOI:10.3389/fvets.2024.1434627
    3. Agbemelo-Tsomafo C, Adjei S, Kusi KA, et al. Prevalence of Leucocytozoon infection in domestic birds in Ghana. PLoS One, 2023, 18(11): e0294066. DOI:10.1371/journal.pone.0294066
    4. González-Olvera M, Hernandez-Colina A, Chantrey J, et al. A non-invasive feather-based methodology for the detection of blood parasites (Haemosporida). Sci Rep, 2023, 13(1): 16712. DOI:10.1038/s41598-023-43932-y
    5. Boonchuay K, Thomrongsuwannakij T, Chagas CRF, et al. Prevalence and Diversity of Blood Parasites (Plasmodium, Leucocytozoon and Trypanosoma) in Backyard Chickens (Gallus gallus domesticus) Raised in Southern Thailand. Animals (Basel), 2023, 13(17): 2798. DOI:10.3390/ani13172798
    6. Tembe D, Malatji MP, Mukaratirwa S. Occurrence, Prevalence, and Distribution of Haemoparasites of Poultry in Sub-Saharan Africa: A Scoping Review. Pathogens, 2023, 12(7): 945. DOI:10.3390/pathogens12070945
    7. Valkiūnas G, Iezhova TA. Insights into the Biology of Leucocytozoon Species (Haemosporida, Leucocytozoidae): Why Is There Slow Research Progress on Agents of Leucocytozoonosis?. Microorganisms, 2023, 11(5): 1251. DOI:10.3390/microorganisms11051251
    8. Li Z, Ren XX, Zhao YJ, et al. First report of haemosporidia and associated risk factors in red junglefowl (Gallus gallus) in China. Parasit Vectors, 2022, 15(1): 275. DOI:10.1186/s13071-022-05389-2
    9. El-Azm KIA, Hamed MF, Matter A, et al. Molecular and pathological characterization of natural co-infection of poultry farms with the recently emerged Leucocytozoon caulleryi and chicken anemia virus in Egypt. Trop Anim Health Prod, 2022, 54(2): 91. DOI:10.1007/s11250-022-03097-8
    10. Pohuang T, Jittimanee S, Junnu S. Pathology and molecular characterization of Leucocytozoon caulleryi from backyard chickens in Khon Kaen Province, Thailand. Vet World, 2021, 14(10): 2634-2639. DOI:10.14202/vetworld.2021.2634-2639
    11. Khumpim P, Chawengkirttikul R, Junsiri W, et al. Molecular detection and genetic diversity of Leucocytozoon sabrazesi in chickens in Thailand. Sci Rep, 2021, 11(1): 16686. DOI:10.1038/s41598-021-96241-7
    12. Piratae S, Vaisusuk K, Chatan W. Prevalence and molecular identification of Leucocytozoon spp. in fighting cocks (Gallus gallus) in Thailand. Parasitol Res, 2021, 120(6): 2149-2155. DOI:10.1007/s00436-021-07131-w
    13. Valkiūnas G, Iezhova TA. Exo-erythrocytic development of avian malaria and related haemosporidian parasites. Malar J, 2017, 16(1): 101. DOI:10.1186/s12936-017-1746-7

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