Circular RNA circ_0040823 inhibits the proliferation of acute myeloid leukemia cells and induces apoptosis by regulating miR‐516b/PTEN

• Published in: The journal of gene medicine 2022-03, Vol.24 (3), p.e3404-n/a
• Main Authors: Wang, Nianxue, Yang, Bin, Jin, Jiao, He, Yu, Wu, Xijun, Yang, Yichen, Zhou, Weijun, He, Zhixu
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Animals; Apoptosis; Apoptosis - genetics; Cell cycle; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Circular RNA; DNA microarrays; Gene Expression Regulation, Neoplastic; Gene therapy; Humans; Immunoprecipitation; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Mice; Mice, Nude; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Peripheral blood; phosphatase and tensin homolog; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; RNA, Circular - genetics; Tensin; Therapeutic targets; Transfection; Tumor suppressor genes; Xenografts
• ISSN: 1099-498X; 1521-2254
• DOI: 10.1002/jgm.3404

Objective Endogenous circular RNAs (circRNAs) and microRNAs (miRNAs) have been shown to regulate the pathogenesis of acute myeloid leukemia (AML). The current study aimed to identify the role of circRNA 0040823 (circ_0040823) in AML. Methods Microarray datasets were analyzed to identify differentially expressed circRNAs in AML patients. Peripheral blood samples were obtained from healthy volunteers and AML patients for the measurement of circ_0040823 and miR‐516b levels. The overexpression or knockdown of a target gene in AML cells was achieved by the transfection with lentiviral vectors or small interfering RNAs. BALB/c nude mice were inoculated with AML cells and monitored for tumor growth. Dual‐luciferase reporter assay, RNA immunoprecipitation, and RNA pull‐down assay were used to determine the binding relationship between circRNA and miRNA. Results circ_0040823 was significantly downregulated in AML patients and leukemia cells. Overexpression of circ_0040823 inhibited AML cell proliferation, and induced apoptosis and cell cycle arrest. Upregulation of circ_0040823 also repressed the growth of xenograft tumors in vivo. circ_0040823 acted as a miR‐516b sponge and regulated key cellular events in leukemia cells via downregulating miR‐516b. Moreover, tumor suppressor phosphatase and tensin homolog (PTEN) was a downstream target of miR‐516b. The inhibition of miR‐516b impaired the proliferation capacity of leukemia cells and induced apoptosis, while PTEN deficiency attenuated these effects. Conclusion This study showed that circ_0040823 inhibited proliferation and induced apoptosis of AML cells by sponging miR‐516b, thereby diminishing the regulatory effect of miR‐516b on PTEN. These findings identified circ_0040823/miR‐516b/PTEN as a new therapeutic target for AML. ‐ Circular RNA 0040823 (circ_0040823) is significantly downregulated in patients with acute myeloid leukemia (AML) and leukemia cells. ‐ Overexpression of circ_0040823 represses the growth of xenograft tumors in vivo. ‐ Upregulation of circ_0040823 also inhibits AML cell proliferation, and induced apoptosis and cell cycle arrest via regulating tumor suppressor phosphatase and tensin homolog and microRNA‐516b.