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Expression of miR-652-3p and Effect on Apoptosis and Drug Sensitivity in Pediatric Acute Lymphoblastic Leukemia
Qian Jiang1, Xiaojing Lu2, Pengli Huang1
1Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Abstract:
MicroRNAs (miRNAs) expression profiles were screened in plasma samples from pediatric patients with acute lymphoblastic leukemia (ALL) and healthy controls, using qRT-PCR-based TaqMan low-density miRNA arrays. MiR-652-3p (a circulating miRNA) was downregulated in new diagnosis (ND) patients compared with healthy controls. The levels of miR652-3p were restored in complete remission (CR) but were downregulated again in disease relapse (RE). The expression pattern of miR-652-3p was validated in bone marrow (BM) samples from other pediatric ALL patients. MiR-652-3p was significantly upregulated in BM when the patients (n=86) achieved CR, as compared with the matched ND samples (p<0.001). Moreover, the miR-652-3p levels in BM decreased again in two patients at RE. In addition, the lymphoblastic leukemia cell lines Reh and RS4:11 were found to have lower levels of miR-625-3p than the normal B-cell line. Overexpression of miR-652-3p using agomir increased the sensitivity to vincristine and cytarabine (all p<0.05) and promoted apoptosis (both p<0.05) in Reh and RS4:11 cells. In conclusion, the results suggested that a low level of miR-652-3p might be involved in the pathogenesis of pediatric ALL. Overexpression of miR-652-3p might suppress lymphoblastic leukemia cells, promoting apoptosis and increasing sensitivity to chemotherapeutic drugs.
Insights
Low levels of microRNA-652-3p (miR-652-3p) are linked to pediatric acute lymphoblastic leukemia (ALL) development. Restoring miR-652-3p levels may suppress leukemia cells and enhance chemotherapy effectiveness.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in cellular processes and disease development.
- Altered miRNA expression is implicated in various cancers, including acute lymphoblastic leukemia (ALL).
- Circulating miRNAs in plasma offer potential as non-invasive biomarkers for pediatric ALL.
Purpose of the Study:
- To investigate the expression profile of miRNAs in pediatric patients with acute lymphoblastic leukemia (ALL).
- To identify specific miRNAs associated with ALL diagnosis, remission, and relapse.
- To evaluate the therapeutic potential of miR-652-3p in ALL treatment.
Main Methods:
- Screening of miRNA expression profiles in plasma samples from pediatric ALL patients and healthy controls using qRT-PCR-based TaqMan low-density miRNA arrays.
- Validation of miR-652-3p expression in bone marrow samples from ALL patients.
- Assessment of miR-652-3p levels in leukemia cell lines and the effect of miR-652-3p overexpression on cell sensitivity to chemotherapy and apoptosis.
Main Results:
- Circulating miR-652-3p was downregulated in newly diagnosed pediatric ALL patients compared to controls.
- miR-652-3p levels were restored in complete remission and decreased again in relapse.
- Overexpression of miR-652-3p in leukemia cells increased sensitivity to vincristine and cytarabine and promoted apoptosis.
Conclusions:
- Low miR-652-3p levels may contribute to the pathogenesis of pediatric ALL.
- miR-652-3p holds potential as a biomarker for monitoring ALL progression and remission.
- Restoring miR-652-3p expression could be a promising therapeutic strategy for pediatric ALL, enhancing apoptosis and chemotherapy response.
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