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The DNA-repair protein APE1 participates with hnRNPA2B1 to motif-enriched and prognostic miRNA secretion

Oncogene (2024)Cite this article

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Abstract

The base excision repair (BER) Apurinic/apyrimidinic endonuclease 1 (APE1) enzyme is endowed with several non-repair activities including miRNAs processing. APE1 is overexpressed in many cancers but its causal role in the tumorigenic processes is largely unknown. We recently described that APE1 can be actively secreted by mammalian cells through exosomes. However, APE1 role in EVs or exosomes is still unknown, especially regarding a putative regulatory function on vesicular small non-coding RNAs. Through dedicated transcriptomic analysis on cellular and vesicular small RNAs of different APE1-depleted cancer cell lines, we found that miRNAs loading into EVs is a regulated process, dependent on APE1, distinctly conveying RNA subsets into vesicles. We identified APE1-dependent secreted miRNAs characterized by enriched sequence motifs and possible binding sites for APE1. In 33 out of 34 APE1-dependent-miRNA precursors, we surprisingly found EXO-motifs and proved that APE1 cooperates with hnRNPA2B1 for the EV-sorting of a subset of miRNAs, including miR-1246, through direct binding to GGAG stretches. Using TCGA-datasets, we showed that these miRNAs identify a signature with high prognostic significance in cancer. In summary, we provided evidence that the ubiquitous DNA-repair enzyme APE1 is part of the EV protein cargo with a novel post-transcriptional role for this ubiquitous DNA-repair enzyme that could explain its role in cancer progression. These findings could open new translational perspectives in cancer biology.

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Fig. 1: Characterisation of EVs and EV-RNA from APE1-silenced cells.
Fig. 2: APE1 depletion affects miRNAs and ncRNAs EV secretion.
Fig. 3: Characterisation of APE1-hnRNPA2B1 interaction.
Fig. 4: APE1 binds to EXO-motif containing miRNAs.
Fig. 5: APE1 interacts with miR-1246 cooperating with hnRNPA2B1.
Fig. 6: APE1 downregulation dysregulates miR-1246 cellular pool.
Fig. 7: Prognostic significance of identified vesicular microRNAs.

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Data availability

Data regarding the RNA-sequencing experiment is publicly available at either raw and count level at NCBI Gene Expression Omnibus Database with GEO accession number GSE230874 (the following secure token has been created to allow review of record GSE230874 while it remains in private status: ozghkmgyjxsvjqv). Code used for performing the analysis will be available upon reasonable request.

Code availability

Data regarding the RNA-sequencing experiment is publicly available at either raw and count level at NCBI Gene Expression Omnibus Database with GEO accession number GSE230874 (the following secure token has been created to allow review of record GSE230874 while it remains in private status: ozghkmgyjxsvjqv). Code used for performing the analysis will be available upon reasonable request.

References

  1. Antoniali G, Malfatti MC, Tell G. Unveiling the non-repair face of the Base Excision Repair pathway in RNA processing: A missing link between DNA repair and gene expression? DNA Repair. 2017;56:65–74.

    Article  CAS  PubMed  Google Scholar 

  2. Malfatti MC, Antoniali G, Codrich M, Burra S, Mangiapane G, Dalla E, et al. New perspectives in cancer biology from a study of canonical and non-canonical functions of base excision repair proteins with a focus on early steps. Mutagenesis. 2020;35:129–49.

    Article  CAS  PubMed  Google Scholar 

  3. Tell G, Demple B. Base excision DNA repair and cancer. Oncotarget. 2015;6:584–5.

    Article  PubMed  Google Scholar 

  4. Dai N, Zhong ZY, Cun YP, Qing Y, Chen C, Jiang P, et al. Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA. Neoplasma. 2013;60:384–94.

    Article  CAS  PubMed  Google Scholar 

  5. Berquist BR, McNeill DR, Wilson DM. Characterization of abasic endonuclease activity of Human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision. J Mol Biol. 2008;379:17–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Simms CL, Zaher HS. Quality control of chemically damaged RNA. Cell Mol Life Sci. 2016;73:3639–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Malfatti MC, Balachander S, Antoniali G, Koh KD, Saint-Pierre C, Gasparutto D, et al. Abasic and oxidized ribonucleotides embedded in DNA are processed by human APE1 and not by RNase H2. Nucleic Acids Res. 2017;45:11193–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Vascotto C, Fantini D, Romanello M, Cesaratto L, Deganuto M, Leonardi A, et al. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol. 2009;29:1834–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tell G, Wilson DM, Lee CH. Intrusion of a DNA repair protein in the rnome world: is this the beginning of a new era? Mol Cell Biol. 2010;30:366–71.

    Article  CAS  PubMed  Google Scholar 

  10. Vascotto C, Cesaratto L, Zeef LAH, Deganuto M, D’Ambrosio C, Scaloni A, et al. Genome-wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional role in mammalian cells. Proteomics. 2009;9:1058–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Antoniali G, Lirussi L, Poletto M, Tell G. Emerging roles of the nucleolus in regulating the DNA damage response: the noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example. Antioxid Redox Signal. 2014;20:621–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Antoniali G, Serra F, Lirussi L, Tanaka M, D’Ambrosio C, Zhang S, et al. Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nat Commun. 2017;8:797.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ayyildiz D, Antoniali G, D’Ambrosio C, Mangiapane G, Dalla E, Scaloni A, et al. Architecture of the human Ape1 interactome defines novel cancers signatures. Sci Rep. 2020;10:28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yang F, Ning Z, Ma L, Liu W, Shao C, Shu Y, et al. Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts. Mol Cancer. 2017;16:148.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cai Y, Yu X, Hu S, Yu J. A brief review on the mechanisms of miRNA regulation. Genomics Proteom Bioinforma. 2009;7:147–54.

    Article  CAS  Google Scholar 

  16. Correia de Sousa M, Gjorgjieva M, Dolicka D, Sobolewski C, Foti M Deciphering miRNAs’ Action through miRNA Editing. Int J Mol Sci. 2019; 20. https://doi.org/10.3390/ijms20246249.

  17. Antoniali G, Dalla E, Mangiapane G, Zhao X, Jing X, Cheng Y, et al. APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b. Cell Mol Life Sci CMLS. 2022;79:446.

    Article  CAS  PubMed  Google Scholar 

  18. Dai N, Cao X-J, Li M-X, Qing Y, Liao L, Lu X-F, et al. Serum APE1 autoantibodies: a novel potential tumor marker and predictor of chemotherapeutic efficacy in non-small cell lung cancer. PloS One. 2013;8:e58001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pascut D, Sukowati CHC, Antoniali G, Mangiapane G, Burra S, Mascaretti LG, et al. Serum AP-endonuclease 1 (sAPE1) as novel biomarker for hepatocellular carcinoma. Oncotarget. 2019;10:383–94.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zhang S, He L, Dai N, Guan W, Shan J, Yang X, et al. Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients. Oncotarget. 2016;7:77482–94.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Shin JH, Choi S, Lee YR, Park MS, Na YG, Irani K, et al. APE1/Ref-1 as a serological biomarker for the detection of bladder cancer. Cancer Res Treat J Korean Cancer Assoc. 2015;47:823–33.

    Article  CAS  Google Scholar 

  22. Mangiapane G, Parolini I, Conte K, Malfatti MC, Corsi J, Sanchez M et al. Enzymatically active apurinic/apyrimidinic endodeoxyribonuclease 1 is released by mammalian cells through exosomes. J Biol Chem. 2021:100569.

  23. Parolini I, Degrassi M, Spadaro F, Caponnetto F, Fecchi K, Mastantuono S et al. Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1. FEBS J. 2024:febs.17088.

  24. Sun Z, Shi K, Yang S, Liu J, Zhou Q, Wang G, et al. Effect of exosomal miRNA on cancer biology and clinical applications. Mol Cancer. 2018;17:147.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, Pérez-Hernández D, Vázquez J, Martin-Cofreces N, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun. 2013;4:2980.

    Article  PubMed  Google Scholar 

  26. Behera J, Tyagi N. Exosomes: mediators of bone diseases, protection, and therapeutics potential. Oncoscience. 2018;5:181–95.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hannafon BN, Ding W-Q. Intercellular communication by exosome-derived microRNAs in cancer. Int J Mol Sci. 2013;14:14240–69.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ramachandran S, Palanisamy V. Horizontal transfer of RNAs: exosomes as mediators of intercellular communication. Wiley Interdiscip Rev RNA. 2012;3:286–93.

    Article  CAS  PubMed  Google Scholar 

  29. Bebelman MP, Smit MJ, Pegtel DM, Baglio SR. Biogenesis and function of extracellular vesicles in cancer. Pharm Ther. 2018;188:1–11.

    Article  CAS  Google Scholar 

  30. Vyas N, Dhawan J. Exosomes: mobile platforms for targeted and synergistic signaling across cell boundaries. Cell Mol Life Sci. 2017;74:1567–76.

    Article  CAS  PubMed  Google Scholar 

  31. Chiu Y-C, Tsai M-H, Chou W-C, Liu Y-C, Kuo Y-Y, Hou H-A, et al. Prognostic significance of NPM1 mutation-modulated microRNA−mRNA regulation in acute myeloid leukemia. Leukemia. 2016;30:274–84.

    Article  CAS  PubMed  Google Scholar 

  32. Fabbiano F, Corsi J, Gurrieri E, Trevisan C, Notarangelo M, D’Agostino VG RNA packaging into extracellular vesicles: An orchestra of RNA‐binding proteins? J Extracell Vesicles. 2020; 10. https://doi.org/10.1002/jev2.12043.

  33. Wang K, Zhang S, Weber J, Baxter D, Galas DJ. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res. 2010;38:7248–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Masani S, Han L, Yu K. Apurinic/apyrimidinic endonuclease 1 is the essential nuclease during immunoglobulin class switch recombination. Mol Cell Biol. 2013;33:1468–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Notarangelo M, Zucal C, Modelska A, Pesce I, Scarduelli G, Potrich C, et al. Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood. EBioMedicine. 2019;43:114–26.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Notarangelo M, Ferrara D, Potrich C, Lunelli L, Vanzetti L, Provenzani A, et al. Rapid nickel-based isolation of extracellular vesicles from different biological fluids. Bio-Protoc. 2020;10:e3512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Karagkouni D, Paraskevopoulou MD, Chatzopoulos S, Vlachos IS, Tastsoglou S, Kanellos I, et al. DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA-gene interactions. Nucleic Acids Res. 2018;46:D239–45.

    Article  CAS  PubMed  Google Scholar 

  38. Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T. miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 2009;37:D105–110.

    Article  CAS  PubMed  Google Scholar 

  39. Reimand J, Arak T, Adler P, Kolberg L, Reisberg S, Peterson H, et al. g:Profiler-a web server for functional interpretation of gene lists (2016 update). Nucleic Acids Res. 2016;44:W83–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hobor F, Dallmann A, Ball NJ, Cicchini C, Battistelli C, Ogrodowicz RW, et al. A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets. Nat Commun. 2018;9:831.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wolfgang Kopp [Aut C. motifcounter. 2017. https://doi.org/10.18129/B9.BIOC.MOTIFCOUNTER.

  42. Garcia-Martin R, Wang G, Brandão BB, Zanotto TM, Shah S, Kumar Patel S, et al. MicroRNA sequence codes for small extracellular vesicle release and cellular retention. Nature. 2022;601:446–51.

    Article  CAS  PubMed  Google Scholar 

  43. Wu B, Su S, Patil DP, Liu H, Gan J, Jaffrey SR, et al. Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nat Commun. 2018;9:420.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000;25:25–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. The Gene Ontology Consortium. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res. 2019;47:D330–38.

    Article  Google Scholar 

  46. Karp PD, Billington R, Caspi R, Fulcher CA, Latendresse M, Kothari A, et al. The BioCyc collection of microbial genomes and metabolic pathways. Brief Bioinform. 2019;20:1085–93.

    Article  CAS  PubMed  Google Scholar 

  47. Martinez FJ, Pratt GA, Van Nostrand EL, Batra R, Huelga SC, Kapeli K, et al. Protein-RNA networks regulated by normal and ALS-associated mutant HNRNPA2B1 in the nervous system. Neuron. 2016;92:780–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Geissler R, Simkin A, Floss D, Patel R, Fogarty EA, Scheller J, et al. A widespread sequence-specific mRNA decay pathway mediated by hnRNPs A1 and A2/B1. Genes Dev. 2016;30:1070–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Alarcón CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF. HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell. 2015;162:1299–308.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Vascotto C, Bisetto E, Li M, Zeef LAH, D’Ambrosio C, Domenis R, et al. Knock-in reconstitution studies reveal an unexpected role of Cys-65 in regulating APE1/Ref-1 subcellular trafficking and function. Mol Biol Cell. 2011;22:3887–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Barzilay G, Walker LJ, Robson CN, Hickson ID. Site-directed mutagenesis of the human DNA repair enzyme HAP1: identification of residues important for AP endonuclease and RNase H activity. Nucleic Acids Res. 1995;23:1544–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yamamori T, DeRicco J, Naqvi A, Hoffman TA, Mattagajasingh I, Kasuno K, et al. SIRT1 deacetylates APE1 and regulates cellular base excision repair. Nucleic Acids Res. 2010;38:832–45.

    Article  CAS  PubMed  Google Scholar 

  53. Lirussi L, Antoniali G, Vascotto C, D’Ambrosio C, Poletto M, Romanello M, et al. Nucleolar accumulation of APE1 depends on charged lysine residues that undergo acetylation upon genotoxic stress and modulate its BER activity in cells. Mol Biol Cell. 2012;23:4079–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Fantini D, Vascotto C, Marasco D, D’Ambrosio C, Romanello M, Vitagliano L, et al. Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions. Nucleic Acids Res. 2010;38:8239–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rybarczyk A, Lehmann T, Iwańczyk-Skalska E, Juzwa W, Pławski A, Kopciuch K, et al. In silico and in vitro analysis of the impact of single substitutions within EXO-motifs on Hsa-MiR-1246 intercellular transfer in breast cancer cell. J Appl Genet. 2023;64:105–24.

    Article  CAS  PubMed  Google Scholar 

  56. Ghafouri-Fard S, Khoshbakht T, Hussen BM, Taheri M, Samadian M. A review on the role of miR-1246 in the pathoetiology of different cancers. Front Mol Biosci. 2021;8:771835.

    Article  CAS  PubMed  Google Scholar 

  57. Liu Y, Shi S-L. The roles of hnRNP A2/B1 in RNA biology and disease. Wiley Interdiscip Rev RNA. 2021;12:e1612.

    Article  CAS  PubMed  Google Scholar 

  58. Tell G, Fantini D, Quadrifoglio F. Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment. Cell Mol Life Sci CMLS. 2010;67:3589–608.

    Article  CAS  PubMed  Google Scholar 

  59. Indrieri A, Carrella S, Carotenuto P, Banfi S, Franco B. The pervasive role of the miR-181 family in development, neurodegeneration, and cancer. Int J Mol Sci. 2020;21:2092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lieb V, Weigelt K, Scheinost L, Fischer K, Greither T, Marcou M, et al. Serum levels of miR-320 family members are associated with clinical parameters and diagnosis in prostate cancer patients. Oncotarget. 2018;9:10402–16.

    Article  PubMed  Google Scholar 

  61. O’Grady T, Njock M-S, Lion M, Bruyr J, Mariavelle E, Galvan B, et al. Sorting and packaging of RNA into extracellular vesicles shape intracellular transcript levels. BMC Biol. 2022;20:72.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Lee H, Li C, Zhang Y, Zhang D, Otterbein LE, Jin Y. Caveolin-1 selectively regulates microRNA sorting into microvesicles after noxious stimuli. J Exp Med. 2019;216:2202–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Yuan C-L, He F, Ye J-Z, Wu H-N, Zhang J-Y, Liu Z-H, et al. APE1 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis. Oncotarget. 2017;8:59720–8.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Tell G, Wilson DM. Targeting DNA repair proteins for cancer treatment. Cell Mol Life Sci. 2010;67:3569–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhang Z, Wu Z, Shi X, Guo D, Cheng Y, Gao J, et al. Research progress in human AP endonuclease 1: structure, catalytic mechanism, and inhibitors. Curr Protein Pept Sci. 2022;23:77–88.

    Article  CAS  PubMed  Google Scholar 

  66. Mijit M, Caston R, Gampala S, Fishel ML, Fehrenbacher J, Kelley MR. APE1/Ref-1 - one target with multiple indications: emerging aspects and new directions. J Cell Signal. 2021;2:151–61.

    PubMed  PubMed Central  Google Scholar 

  67. Codrich M, Comelli M, Malfatti MC, Mio C, Ayyildiz D, Zhang C, et al. Inhibition of APE1-endonuclease activity affects cell metabolism in colon cancer cells via a p53-dependent pathway. DNA Repair. 2019;82:102675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work was supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC) [grant number IG19862] to GT and through the support of the Departmental Strategic Plan (PSD) of the University of Udine—Interdepartmental Project on Artificial Intelligence (2020–25) and by additional grants from the University of Udine (‘Bando Ricerca Collaborativa’ granted by European Community—NextGenerationEU) and from the Consorzio Interuniversitario Biotecnologie—C.I.B.—(ex D.M. MUR n.1059 del 09.08.21: “L’INNOVAZIONE DELLE BIOTECNOLOGIE NELL’ERA DELLA MEDICINA DI PRECISIONE, DEI CAMBIAMENTI CLIMATICI E DELL’ECONOMIA CIRCOLARE”) to G.T. Fondazione CARITRO (CASSA DI RISPARMIO TRENTO E ROVERETO) to VGD. CIBIO NGS Facility was supported by the European Regional Development Fund (ERDF) 2014–2020. GC is a PhD student of the Molecular Biomedicine Program of University of Trieste. SP would like to thank the International Center for Genetic Engineering and Biotechnology (ICGEB) for the financial support.

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Authors and Affiliations

  1. Laboratory of Molecular Biology and DNA repair, Department of Medicine (DMED), University of Udine, Udine, Italy

    Giovanna Mangiapane, Emiliano Dalla, Monica Degrassi, Giulia Antoniali, Nicolò Gualandi & Gianluca Tell

  2. Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy

    Michela Notarangelo, Fabrizio Fabbiano & Vito Giuseppe D’Agostino

  3. Yale University School of Medicine, New Haven, CT, USA

    Michela Notarangelo

  4. Computational Biology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy

    Giulia Canarutto & Silvano Piazza

  5. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy

    Giulia Canarutto & Silvano Piazza

  6. Next Generation Sequencing Facility, Department CIBIO, University of Trento, Trento, Italy

    Veronica De Sanctis

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  1. Giovanna Mangiapane
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Contributions

GT and VDA designed and conceived the study and supervised the experiments; GM performed most of the experiments, analyzed the data, and critically contributed to the interpretation of the results; MN contributed to the experiments on EVs RNA characterization and prepared the NGS libraries, FF contributed to the experiments on EV-RNA characterization; GC, ED, NG, SP performed the bioinformatics analysis; S.P. supervised the Bioinformatic analyses; VDS supported in libraries preparation and performed the NGS sequencing; MDG performed EMSA experiments; GA helped with EMSA analysis; GM, VDA, SP and GT mainly wrote the manuscript. All authors critically read and approved the final version of the manuscript.

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Correspondence to Silvano Piazza, Vito Giuseppe D’Agostino or Gianluca Tell.

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Mangiapane, G., Notarangelo, M., Canarutto, G. et al. The DNA-repair protein APE1 participates with hnRNPA2B1 to motif-enriched and prognostic miRNA secretion. Oncogene (2024). https://doi.org/10.1038/s41388-024-03039-8

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