Molecular biology reports · 2026
Hsa_circ_0029325 drives imatinib resistance via the CDCA4/AKT axis in chronic myeloid leukemia.
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Lan Xiaoxu, Sun Hang, Mu Yulong, Hou Xiaoqing, Ti Chenhui, Sun Weimiao, Xie Shuyang, Li Youjie, Sun Yunxiao
Аннотация
BACKGROUND: Imatinib (IM) resistance poses a major unresolved clinical challenge in chronic myeloid leukemia (CML) treatment, significantly compromising patient prognosis. This study aims to elucidate the role of cell division cycle-associated protein 4 (CDCA4) in IM resistance and the underlying molecular mechanisms in CML.
METHODS AND RESULTS: Pan-cancer analysis revealed that high CDCA4 expression was significantly associated with shorter overall survival in multiple cancer types. Quantitative real-time PCR demonstrated upregulated CDCA4 expression in both peripheral blood samples from CML patients and IM-resistant cell lines. CCK-8 assays showed that CDCA4 overexpression markedly enhanced IM resistance and promoted cell proliferation in CML cells. Mechanistic investigations indicated that CDCA4 is associated with hyperactivation of the AKT-mTOR signaling axis and concurrent suppression of basal autophagy, a phenotype that correlates with imatinib chemoresistance in CML cells. Subsequent molecular profiling identified a circ_0029325-dependent regulatory circuit that governs CDCA4 expression levels.
CONCLUSIONS: Our findings clarify the critical function of CDCA4 in CML IM resistance via the AKT-mTOR/autophagy axis and reveal its upstream circ_0029325 regulatory mechanism. This work provides promising potential biomarkers and therapeutic targets for improving CML treatment outcomes.
METHODS AND RESULTS: Pan-cancer analysis revealed that high CDCA4 expression was significantly associated with shorter overall survival in multiple cancer types. Quantitative real-time PCR demonstrated upregulated CDCA4 expression in both peripheral blood samples from CML patients and IM-resistant cell lines. CCK-8 assays showed that CDCA4 overexpression markedly enhanced IM resistance and promoted cell proliferation in CML cells. Mechanistic investigations indicated that CDCA4 is associated with hyperactivation of the AKT-mTOR signaling axis and concurrent suppression of basal autophagy, a phenotype that correlates with imatinib chemoresistance in CML cells. Subsequent molecular profiling identified a circ_0029325-dependent regulatory circuit that governs CDCA4 expression levels.
CONCLUSIONS: Our findings clarify the critical function of CDCA4 in CML IM resistance via the AKT-mTOR/autophagy axis and reveal its upstream circ_0029325 regulatory mechanism. This work provides promising potential biomarkers and therapeutic targets for improving CML treatment outcomes.