Beijing 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.
Maternity and Child Care Hospital of Henan Province, Zhengzhou, Henan 450052, China.
Biomed Res Int. 2018 Jun 5;2018:5724686. doi: 10.1155/2018/5724686. eCollection 2018.
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 (=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.
miRNAs(miRNAs)表达谱在小儿急性淋巴细胞白血病(ALL)患者和健康对照者的血浆样本中进行了筛选,使用基于 qRT-PCR 的 TaqMan 低密度 miRNA 阵列。与健康对照者相比,新诊断(ND)患者的 miR-652-3p(一种循环 miRNA)下调。在完全缓解(CR)时,miR652-3p 的水平得到恢复,但在疾病复发(RE)时再次下调。miR-652-3p 的表达模式在其他小儿 ALL 患者的骨髓(BM)样本中得到了验证。与匹配的 ND 样本相比,当患者(=86)达到 CR 时,BM 中 miR-652-3p 明显上调(p<0.001)。此外,在两个患者的 RE 中,BM 中的 miR-652-3p 水平再次下降。此外,发现淋巴母细胞白血病细胞系 Reh 和 RS4:11 的 miR-625-3p 水平低于正常 B 细胞系。用 agomir 过表达 miR-652-3p 可提高 Reh 和 RS4:11 细胞对长春新碱和阿糖胞苷的敏感性(均 p<0.05)并促进细胞凋亡(均 p<0.05)。总之,结果表明 miR-652-3p 水平降低可能参与小儿 ALL 的发病机制。过表达 miR-652-3p 可能抑制淋巴母细胞白血病细胞,促进细胞凋亡并增加对化疗药物的敏感性。