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      Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target

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          Abstract

          YARS is responsible for catalysing the binding of tyrosine to its cognate tRNA and plays a crucial role in basic biosynthesis. However, its biological functions in bladder cancer remains to be proven. We analysed variations in YARS1 expression and survival in bladder cancer using multiple data sets, including TCGA‐BLCA, GSE13507 and bladder cancer‐specific tissue microarrays. Furthermore, we explored the biological functions of YARS1 using transcriptome data. Our findings revealed a noteworthy correlation between YARS1 and immune infiltration in bladder cancer, as determined using the XCELL algorithm and single‐cell analysis. In addition, we employed the TIDE algorithm to evaluate the responsiveness of different cohorts to immune checkpoint therapy. We investigated the regulatory associations between YARS1 and various aspects of bladder cancer, including senescence, ferroptosis and stemness. Finally, we established a ceRNA network that is directly linked to the overall prognosis, YARS1 can serve as a prognostic biomarker for bladder cancer; its interaction with MYC has implications for bladder cancer cell senescence, ferroptosis and stemness. Moreover, the identified ceRNA network has potential as a therapeutic target in bladder cancer.

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          Most cited references39

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          Ferroptosis: an iron-dependent form of nonapoptotic cell death.

          Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Robust enumeration of cell subsets from tissue expression profiles

            We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA mixtures for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).
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              starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data

              Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g. lncRNAs, pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been implicated in cell-fate determination and in various human diseases, surprisingly little is known about the regulatory interaction networks among the multiple classes of RNAs. In this study, we developed starBase v2.0 (http://starbase.sysu.edu.cn/) to systematically identify the RNA–RNA and protein–RNA interaction networks from 108 CLIP-Seq (PAR-CLIP, HITS-CLIP, iCLIP, CLASH) data sets generated by 37 independent studies. By analyzing millions of RNA-binding protein binding sites, we identified ∼9000 miRNA-circRNA, 16 000 miRNA-pseudogene and 285 000 protein–RNA regulatory relationships. Moreover, starBase v2.0 has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and miRNA-lncRNA interaction networks to date. We identified ∼10 000 ceRNA pairs from CLIP-supported miRNA target sites. By combining 13 functional genomic annotations, we developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from the miRNA-mediated regulatory networks. Finally, we developed interactive web implementations to provide visualization, analysis and downloading of the aforementioned large-scale data sets. This study will greatly expand our understanding of ncRNA functions and their coordinated regulatory networks.
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                Author and article information

                Contributors
                dingbeichen@hrbmu.edu.cn
                002051@hrbmu.edu.cn
                Journal
                J Cell Mol Med
                J Cell Mol Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                20 March 2024
                April 2024
                : 28
                : 7 ( doiID: 10.1111/jcmm.v28.7 )
                : e18213
                Affiliations
                [ 1 ] Department of Urology The First Affiliated Hospital of Harbin Medical University Harbin China
                Author notes
                [*] [* ] Correspondence

                MingHua Ren and BeiChen Ding, Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

                Email: 002051@ 123456hrbmu.edu.cn and dingbeichen@ 123456hrbmu.edu.cn

                Author information
                https://orcid.org/0000-0002-0996-096X
                https://orcid.org/0009-0004-1602-5146
                Article
                JCMM18213 JCMM-12-2023-150.R1
                10.1111/jcmm.18213
                10951887
                38506098
                de8c86b9-35fc-4c05-872f-4f724cd83b77
                © 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 February 2024
                : 19 December 2023
                : 16 February 2024
                Page count
                Figures: 10, Tables: 1, Pages: 20, Words: 7741
                Funding
                Funded by: Natural Science Foundation of Heilongjiang Province , doi 10.13039/501100005046;
                Award ID: LH2019H030
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82002680
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                April 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.9 mode:remove_FC converted:20.03.2024

                Molecular medicine
                cerna,dna methylation,immune infiltration,prognosis,senescence
                Molecular medicine
                cerna, dna methylation, immune infiltration, prognosis, senescence

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