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<p>Pediatric acute lymphoblastic leukemia (ALL) is the most prevalent hematologic malignancy in children. This study aimed to investigate the diagnostic value and functional role of serum microRNA-493-3p (miR-493-3p) in pediatric ALL.&#xa0;Serum miR-493-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in103 ALL patients and 85 healthy controls. Bioinformatic tools were used to screen potential target genes of miR-493-3p, and dual-luciferase reporter assays were performed for validation. Functional experiments were conducted by regulating miR-493-3p and its target gene expression to assess changes in leukemic cell malignant phenotypes.&#xa0;Serum miR-493-3p expression was notably downregulated in ALL patients compared with healthy controls (<i>P</i> &lt; 0.001), demonstrating good diagnostic accuracy with an area under the curve (AUC) of 0.881. Low miR-493-3p expression was associated with advanced risk stratification (<i>P</i> = 0.001) and poor survival (<i>P</i> &lt; 0.05). Mechanistically, we identified Dpy-30 histone methyltransferase complex regulatory subunit (DPY30) as a direct target of miR-493-3p, showing an inverse correlation in clinical samples (<i>r</i>=-0.755, <i>P</i> &lt; 0.001). Functional experiments revealed that miR-493-3p overexpression suppressed leukemic cell proliferation and invasion (<i>P</i> &lt; 0.001) while promoting apoptosis through targeting DPY30, effects that were partially reversed by DPY30 restoration.&#xa0;Serum miR-493-3p serves as a promising noninvasive biomarker for pediatric ALL diagnosis and prognosis Our findings demonstrate that miR-493-3p functions as a tumor suppressor in ALL by targeting DPY30, suggesting the miR-493-3p/DPY30 axis as a potential therapeutic target for ALL treatment.</p>

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Serum miR-493-3p as a diagnostic biomarker and epigenetic regulator targeting DPY30 in pediatric acute lymphoblastic leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Hong Yang,
  • Yong Xu,
  • Xiaoying Zhang,
  • Yanli Wang,
  • Zhaojian Li

摘要

Pediatric acute lymphoblastic leukemia (ALL) is the most prevalent hematologic malignancy in children. This study aimed to investigate the diagnostic value and functional role of serum microRNA-493-3p (miR-493-3p) in pediatric ALL. Serum miR-493-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in103 ALL patients and 85 healthy controls. Bioinformatic tools were used to screen potential target genes of miR-493-3p, and dual-luciferase reporter assays were performed for validation. Functional experiments were conducted by regulating miR-493-3p and its target gene expression to assess changes in leukemic cell malignant phenotypes. Serum miR-493-3p expression was notably downregulated in ALL patients compared with healthy controls (P < 0.001), demonstrating good diagnostic accuracy with an area under the curve (AUC) of 0.881. Low miR-493-3p expression was associated with advanced risk stratification (P = 0.001) and poor survival (P < 0.05). Mechanistically, we identified Dpy-30 histone methyltransferase complex regulatory subunit (DPY30) as a direct target of miR-493-3p, showing an inverse correlation in clinical samples (r=-0.755, P < 0.001). Functional experiments revealed that miR-493-3p overexpression suppressed leukemic cell proliferation and invasion (P < 0.001) while promoting apoptosis through targeting DPY30, effects that were partially reversed by DPY30 restoration. Serum miR-493-3p serves as a promising noninvasive biomarker for pediatric ALL diagnosis and prognosis Our findings demonstrate that miR-493-3p functions as a tumor suppressor in ALL by targeting DPY30, suggesting the miR-493-3p/DPY30 axis as a potential therapeutic target for ALL treatment.