Circ_0009910 sponges miR-491-5p to promote acute myeloid leukemia progression through modulating B4GALT5 expression and PI3K/AKT signaling pathway

Acute myeloid leukemia (AML) is a heterogeneous group of leukemias with an overall poor prognosis. Circular RNAs (circRNAs) have been verified to play important regulatory roles in AML progression. However, the role and molecular mechanism of circ_0009910 in AML development have not be completely clarified.

Circ_0009910 could suppress the proliferation, sphere formation, and autophagy and accelerated apoptosis by modulating B4GALT5 expression and activating the PI3K/AKT signaling pathway via sponging miR-491-5p in AML cells, suggesting that circ_0009910 might be a potential biomarker for the treatment of AML.

The expression levels of circ_0009910, microRNA-491-5p (miR-491-5p), and β-1, 4-galactosyltransferase 5 (B4GALT5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell proliferation and self-renewal ability were assessed via Cell Counting Kit-8 (CCK-8) and sphere formation assay. Cell cycle distribution and cell apoptosis were evaluated by flow cytometry. Caspase-3 activity was tested by Caspase-3 Activity Assay Kit. Western blot was used to examine the protein levels of autophagy-related markers and PI3K/AKT pathway-related markers. The interaction between miR-491-5p and circ_0009910 or B4GALT5 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay.

Circ_0009910 was highly expressed in AML tissues and cells. Silenced circ_0009910 could significantly inhibit the proliferation, sphere formation, and autophagy and promoted the apoptosis of AML cells. Circ_0009910 bound to miR-491-5p in AML cells, and circ_0009910 promoted AML progression partly through sponging miR-491-5p in vitro. B4GALT5 was a target of miR-491-5p, and miR-491-5p overexpression-mediated influences in AML cells were effectually overturned by the addition of B4GALT5 overexpression plasmid. Furthermore, circ_0009910 could regulate the expression of B4GALT5 by downregulating miR-491-5p in AML cells. Additionally, circ_0009910 could activate the PI3K/AKT signaling pathway by sponging miR-491-5p.