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Serum miR-493-3p as a diagnostic biomarker and epigenetic regulator targeting DPY30 in pediatric acute lymphoblastic
Hong Yang1, Yong Xu2, Xiaoying Zhang3
1Department of Pediatrics, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, 100074, China.
Abstract:
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.
Insights
Serum microRNA-493-3p (miR-493-3p) is downregulated in pediatric acute lymphoblastic leukemia (ALL). Lower miR-493-3p levels indicate poor prognosis and can help diagnose ALL, suggesting a potential therapeutic target.
Area of Science:
- Pediatric Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer.
- Identifying reliable biomarkers for ALL diagnosis and prognosis is crucial.
Purpose of the Study:
- To investigate the diagnostic value of serum microRNA-493-3p (miR-493-3p) in pediatric ALL.
- To explore the functional role of miR-493-3p in ALL pathogenesis.
Main Methods:
- Serum miR-493-3p levels were quantified using qRT-PCR in 103 ALL patients and 85 healthy controls.
- Bioinformatic analysis and dual-luciferase reporter assays identified DPY30 as a direct target of miR-493-3p.
- Functional experiments assessed the impact of miR-493-3p and DPY30 on leukemic cell phenotypes.
Main Results:
- Serum miR-493-3p was significantly downregulated in ALL patients (AUC=0.881) and associated with advanced risk and poor survival.
- miR-493-3p directly targets DPY30, with inverse correlation observed in clinical samples.
- Overexpression of miR-493-3p suppressed proliferation and invasion, and promoted apoptosis in ALL cells by targeting DPY30.
Conclusions:
- Serum miR-493-3p is a promising noninvasive biomarker for pediatric ALL diagnosis and prognosis.
- The miR-493-3p/DPY30 axis acts as a tumor suppressor mechanism in ALL.
- Targeting the miR-493-3p/DPY30 pathway may offer a novel therapeutic strategy for ALL.
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