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oai:figshare.com:article/33871873 2026-09-17T05:33:24Z category_19 portal_316 item_type_3 month_year_09_2026

Supplementary file 3_CircHIPK3 promotes the progression of B-cell acute lymphoblastic leukemia in children by binding to STAT3.xlsx Yu Zheng (2950) Yunpeng Li (2141650) Xiuli Zhu (12073669) Yan Chen (4308) Yuqiao Diao (25002064) Pharmacology B-cell acute lymphoblastic leukemia CircHIPK3 leukemic infiltration STAT3 treatment Background<p>Circular RNAs (circRNAs) have emerged as critical post-transcriptional regulators in hematological malignancies; however, the specific role and molecular mechanism of circHIPK3 in pediatric B-cell acute lymphoblastic leukemia (B-ALL) remain unexplored.</p>Methods<p>circHIPK3 expression was profiled in clinical B-ALL specimens and cell lines. The biological functions were evaluated using CCK-8, flow cytometry, and in vivo NOD/SCID xenograft models for leukemic infiltration assessment. Mechanistic interactions were deciphered via RNA immunoprecipitation (RIP), RNA pull-down, and ubiquitination assays.</p>Results<p>CircHIPK3 was aberrantly upregulated in B-ALL tissues and cells, exhibiting exceptional stability and predominant cytoplasmic localization. CircHIPK3 silencing significantly impaired leukemic cell proliferation, induced G0/G1 cell cycle arrest, and triggered apoptosis. Mechanistically, we identified a direct physical association between cytoplasmic circHIPK3 and STAT3. CircHIPK3 did not alter STAT3 transcription but rather acted as a protein scaffold that shielded STAT3 from ubiquitin-mediated proteasomal degradation, thereby enhancing its protein stability. Ectopic STAT3 expression reversed the tumor-suppressive phenotypes caused by circHIPK3 deficiency. Consistently, circHIPK3 knockdown attenuated leukemic infiltration in xenograft mice.</p>Conclusion<p>Our findings characterize circHIPK3 as a potent oncogenic driver in B-ALL that functions by stabilizing STAT3 via the ubiquitin-proteasome pathway. Targeting the circHIPK3/STAT3 axis may represent a potential therapeutic strategy for B-ALL treatment.</p> 2026-09-17T05:33:24Z Dataset Dataset 10.3389/fphar.2026.1884978.s004 https://figshare.com/articles/dataset/Supplementary_file_3_CircHIPK3_promotes_the_progression_of_B-cell_acute_lymphoblastic_leukemia_in_children_by_binding_to_STAT3_xlsx/33871873 CC BY 4.0