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Mechanism of circADD2 as ceRNA in Childhood Acute Lymphoblastic Leukemia.

ABSTRACT: Background: Acute lymphocytic leukemia (ALL) is the most common malignant tumor in children. Increasing evidence suggests that circular RNAs (circRNAs) play critical regulatory roles in tumor biology. However, the expression patterns and roles of circRNAs in childhood acute lymphoblastic leukemia (ALL) remain largely unknown. Methods: circADD2 was selected by microarray assay and confirmed by qRT-PCR; in vitro effects of circADD2 were determined by CCK-8 and flow cytometry; while mice subcutaneous tumor model was designed for in vivo analysis. RNA immunoprecipitation and dual-luciferase assay were applied for mechanistic study. Protein levels were examined by Western blot assay. Results: circADD2 was down-regulated in ALL tissues and cell lines. Overexpression of circADD2 inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. Briefly, circADD2 could directly sponge miR-149-5p, and the level of AKT2, a target gene of miR-149-5p, was downregulated by circADD2. Conclusion: circADD2, as a tumor suppressor in ALL, can sponge miR-149-5p, and may serve as a potential biomarker for the diagnosis or treatment of ALL.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC8155473 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Mechanism of circADD2 as ceRNA in Childhood Acute Lymphoblastic Leukemia.

Zhu Yuting Y Ma Xiaopeng X Zhang Heng H Wu Yijun Y Kang Meiyun M Fang Yongjun Y Xue Yao Y

Frontiers in cell and developmental biology 20210513

Background: Acute lymphocytic leukemia (ALL) is the most common malignant tumor in children. Increasing evidence suggests that circular RNAs (circRNAs) play critical regulatory roles in tumor biology. However, the expression patterns and roles of circRNAs in childhood acute lymphoblastic leukemia (ALL) remain largely unknown. Methods: circADD2 was selected by microarray assay and confirmed by qRT-PCR; in vitro effects of circADD2 were determined by CCK-8 and flow cytometry; ...[more]

PMID: 34055775

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Project description:BackgroundProphylactic cranial irradiation has been a standard treatment in children with acute lymphoblastic leukemia (ALL) who are at high risk for central nervous system (CNS) relapse.MethodsWe conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted from treatment in all children with newly diagnosed ALL. A total of 498 patients who could be evaluated were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission-induction treatment. The duration of continuous complete remission in the 71 patients who previously would have received prophylactic cranial irradiation was compared with that of 56 historical controls who received it.ResultsThe 5-year event-free and overall survival probabilities for all 498 patients were 85.6% (95% confidence interval [CI], 79.9 to 91.3) and 93.5% (95% CI, 89.8 to 97.2), respectively. The 5-year cumulative risk of isolated CNS relapse was 2.7% (95% CI, 1.1 to 4.3), and that of any CNS relapse (including isolated relapse and combined relapse) was 3.9% (95% CI, 1.9 to 5.9). The 71 patients had significantly longer continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remained in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blast cells at diagnosis and a high level of minimal residual disease (> or = 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the genetic abnormality t(1;19)(TCF3-PBX1), any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection.ConclusionsWith effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted from the treatment of childhood ALL. (ClinicalTrials.gov number, NCT00137111.)

Dataset Information

Mechanism of circADD2 as ceRNA in Childhood Acute Lymphoblastic Leukemia.

Publications

Mechanism of circADD2 as ceRNA in Childhood Acute Lymphoblastic Leukemia.

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