Identification of non-coding RNA regulatory networks in pediatric acute myeloid leukemia reveals circ-0004136 could promote cell proliferation by sponging miR-142

D.-M. Yuan, J. Ma, W.-B. Fang

Department of Pediatrics, Zhongshan Hospital Affiliated to Fudan University Qingpu Branch, Shanghai, China. nqyi16@163.com

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• Hematology

OBJECTIVE: Abnormal expression of circular RNAs (circRNAs) has been observed in various biological processes and cancer pathogenesis. However, the expression of circRNAs in pediatric acute myeloid leukemia (AML) remains largely unknown so far.

PATIENTS AND METHODS: Twelve bone marrow samples from pediatric AML patients and healthy controls were analyzed using Agilent circRNA microarray (n = 6, respectively). The circRNAs profiles and regulatory networks were analyzed by integrated bioinformatics methods. Functional analysis (Gene Ontology and KEGG) was performed by KOBAS. The expression of circRNA in patient samples was validated via qRT-PCR assay (n > 30). Luciferase reporter assay was performed to validate the binding of miRNAs. CCK8 and colony formation assay were conducted to measure cell proliferation.

RESULTS: A total of 273 circRNAs were upregulated in AML and 296 were downregulated (Fold change > 2, p-value < 0.05), the majority of these circRNAs were distributed among chr1, chr6, and chr16, while few in chr13 and chr21. Top 20 differentially expressed circRNAs were chosen to build circRNAs-miRNAs regulatory relationships. Bioinformatics algorithms indicated that circ-0004136 acts as a sponge for several pediatric AML-related miRNAs. Target genes involved in the circ0004136-miRNA-mRNA network were enriched in leukemia-related functions and signaling pathways. Circ-0004136 was found to be significantly upregulated in pediatric AML and could sponge AML-related miRNAs, including miR-29a and miR-142. Furthermore, circ-0004136 was demonstrated to promote the proliferation of AML by sponging miR-142.

CONCLUSIONS: Taken together, this study revealed the circRNAs expression profile and regulatory networks of circRNAs-miRNAs-mRNAs in pediatric AML for the first time. Circ-0004136 was significantly upregulated in pediatric AML and could promote cell proliferation by sponging miR-142.

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