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Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with a poor prognosis, and overcoming chemotherapy resistance poses a significant clinical challenge. This study aimed to clarify the roles of <jats:italic>ADAR1<\/jats:italic> in tumour resistance to cisplatin in iCCA. We discovered that <jats:italic>ADAR1<\/jats:italic> expression is elevated in iCCA patients, particularly in those resistant to cisplatin, and associated with poor clinical outcomes. Downregulation of <jats:italic>ADAR1<\/jats:italic> can increase the sensitivity of iCCA cells to cisplatin treatment, whereas its overexpression has the inverse effect. By integrating RNA sequencing and Sanger sequencing, we identified <jats:italic>BRCA2<\/jats:italic>, a critical DNA damage repair gene, as a downstream target of <jats:italic>ADAR1<\/jats:italic> in iCCA. <jats:italic>ADAR1<\/jats:italic> mediates the A\u2010to\u2010I editing in <jats:italic>BRCA2<\/jats:italic> 3\u2032UTR, inhibiting <jats:italic>miR\u20103157\u20105p<\/jats:italic> binding, consequently increasing <jats:italic>BRCA2<\/jats:italic> mRNA and protein levels. Furthermore, <jats:italic>ADAR1<\/jats:italic> enhances cellular DNA damage repair ability and facilitates cisplatin resistance in iCCA cells. Combining <jats:italic>ADAR1<\/jats:italic> targeting with cisplatin treatment markedly enhances the anticancer efficacy of cisplatin. In conclusion, <jats:italic>ADAR1<\/jats:italic> promotes tumour progression and cisplatin resistance of iCCA. <jats:italic>ADAR1<\/jats:italic> targeting could inform the development of innovative combination therapies for iCCA.<\/jats:p>","DOI":"10.1111\/cpr.13659","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T06:39:06Z","timestamp":1716359946000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<scp>ADAR1<\/scp> promotes cisplatin resistance in intrahepatic cholangiocarcinoma by regulating <scp>BRCA2<\/scp> expression through <scp>A\u2010to\u2010I<\/scp> editing manner"],"prefix":"10.1111","volume":"57","author":[{"given":"Qi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pancreato\u2010Biliary Surgery The First Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 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