Homo sapiens circular RNA 0003602 (Hsa_circ_0003602) accelerates the tumorigenicity of acute myeloid leukemia by modulating miR-502-5p/IGF1R axis.

Abstract

Acute myeloid leukemia (AML) has become a worldwide malignant cancer. We intended to investigate the critical roles and mechanism underlying homo sapiens circular RNA 0003602 (hsa_circ_0003602) in AML progression, especially in tumor cell proliferation, migration, invasion, and apoptosis. Real-time PCR was applied to identify the differential expression of hsa_circ_0003602 and miR-502-5p in AML bone marrow tissues and cell lines. In addition, western blot analysis was employed to determine the levels insulin-like growth factor 1 receptor (IGF1R) protein. The biological behaviors were assessed by CCK-8 cell viability assay, flow cytometry assay for apoptosis detection, and Transwell migration and invasion assay. The relationships between target miRNA and downstream mRNA were investigated by bioinformatics, luciferase reporter assay, and biotin-labeled RNA pull-down assay. Hsa_circ_0003602 was upregulated and predicted poor survival in AML. Knockdown of hsa_circ_0003602 in AML cell lines induced the inhibition of proliferation, migration, and invasion and caused apoptosis. Hsa_circ_0003602 sequestered miR-502-5p by functioning as a competitive endogenous RNA (ceRNA), thereby regulating IGF1R expression. Hsa_circ_0003602 acted as a tumor promoter in AML via miR-502-5p/IGF1R axis. Our study provides evidence that hsa_circ_0003602, miR-502-5p, and IGF1R might form a regulatory axis to affect the carcinogenicity of AML cells and provide potential targets for the treatment of AML.