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We previously reported that the CDH13 oncogene was expressed at low levels in BCR-ABL1-independent resistant CML cell lines. However, its effects on CML resistant cells and mechanisms remain unknown. This study investigated the effects of saRNA-based CDH13 activation on BCR-ABL1-independent imatinib resistance in CML and its underlying mechanism, and proposes a unique treatment method to overcome imatinib resistance. Specifically, this study demonstrated that using the DSIR (Designer of Small Interfering RNA) website tool, saRNAs targeting the CDH13 promoter region were generated and validated using qPCR and western blotting. Among the predicted sequences, C2 and C3 efficiently elevated CDH13 mRNA and protein expression, as well as inhibited the relative vitality of cells and the ability to form clones. After promoting CDH13 expression in K562-IMR cells, it inhabited the NF-\u03baB signaling pathway and induced apoptosis in imatinib-resistant CML cells. LNP-saRNA (C3) was also observed to limit the growth of K562-IMR cells in vivo. From the above, the activation of CDH13 expression by saRNA promotes cell apoptosis by inhibiting the NF-\u03baB signaling pathway to overcome to BCR-ABL1-independent resistance to imatinib in patients with CML.<\/jats:p>","DOI":"10.1038\/s41419-024-07006-9","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T14:09:03Z","timestamp":1724422143000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Small RNA activation of CDH13 expression overcome BCR-ABL1-independent imatinib-resistance and their signaling pathway studies in chronic myeloid leukemia"],"prefix":"10.1038","volume":"15","author":[{"given":"Rui","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingri","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5300-7765","authenticated-orcid":false,"given":"Yubin","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-7870","authenticated-orcid":false,"given":"Jia","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"7006_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-023-00823-9","volume":"13","author":"J Senapati","year":"2023","unstructured":"Senapati J, Sasaki K, Issa GC, Lipton JH, Radich JP, Jabbour E, et al. 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In terms of experimental design, the 4R principle (reduction, refinement, replacement, and responsibility) was followed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"615"}}