Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing
Yifei Cheng1
Rongjie Shi2
Shuai Ben1
Silu Chen1
Shuwei Li1
Junyi Xin3
Meilin Wang4
Gong Cheng2
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,Jiangsu 211166,China2.Department of Urology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China3.Department of Bioinformatics,School of Biomedical Engineering and Informatics,Nanjing Medical University,Nanjing,Jiangsu 211166,China4.Jiangsu Cancer Hospital,Jiangsu Institute of Cancer Research,the Affiliated Cancer Hospital of Nanjing Medical University,Nanjing,Jiangsu 210009,China;The Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou Municipal Hospital,Gusu School,Nanjing Medical University,Suzhou,Jiangsu 215002,China
摘要：The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify risk-associated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4 662 prostate cancer patients and 3 114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10-4)in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.
机标关键词：variationprostategeneticthroughcancerriskcirchibadhenhances
分类号：R737.25(泌尿生殖器肿瘤)
论文发表日期：2024-07-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：12( 中插6,358-368 )
英文信息