Table · dataset · 2026
Supplementary file 3_CircHIPK3 promotes the progression of B-cell acute lymphoblastic leukemia in children by binding to STAT3.xlsx
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Description
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.
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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>
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- DOI doi.org/10.3389/fphar.2026.1884978.s004 ↗
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- Astronomy & Astrophysics · Chemistry · Computer Science & AI · Earth & Environmental Science · Economics & Finance · Engineering · Humanities · Life Sciences · Medicine & Health · Ocean & Atmospheric Science · Social Science
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- Oncology and carcinogenesis 69%
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