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Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related rna splicing

Journal of Biomedical Research 2024年第4期38卷 358-368页

作者： Yifei Cheng Rongjie Shi Shuai Ben Silu Chen Shuwei Li Junyi Xin Meilin Wang Gong Cheng Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China Department of Urology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsu 211166China Jiangsu Cancer Hospital Jiangsu Institute of Cancer Researchthe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsu 210009China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215002China

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 *** first compared expression levels of circrnas between 25 paired PCa and adjacent normal tissues to identify riskassociated circrnas by using the MiOncoCirc *** then used logistic regression models to evaluate associations between genetic variants in candidate circrnas and PCa risk among 4662 prostate cancer patients and 3114 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 *** 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 ***,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting *** conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of rna splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

关键词： genetic variants prostate cancer circrna rna-binding protein rna splicing sing-cell rna sequencing

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