hsa_circ_0001776 regulates the progression of acute myeloid leukemia through the miR-1269b/PTEN axis

Acute myeloid leukemia (AML) is a malignant neoplasm arising from bone marrow hematopoietic stem cells. It is a common subtype of childhood leukemia and remains challenging to cure. Emerging evidence suggests that circular RNAs (circRNAs), a class of noncoding RNAs, play key regulatory roles in tumor biology. Among their various functions, circRNAs often act as 'sponges' for microRNAs (miRNAs), modulating gene expression posttranscriptionally. This study investigates the functional role and clinical relevance of hsa_circ_0001776 in AML.

Three AML cell lines and 22 peripheral blood samples were analyzed. Differential expression analysis of circRNAs in a GSE dataset was performed to identify significantly down- and upregulated candidates, with thresholds set at logFC less than -1 and p < 0.05 for downregulation, and logFC more than 1 and p < 0.05 for upregulation. The back-splice junction of hsa_circ_0001776 was validated using Sanger sequencing. Its circular nature and stability were confirmed via actinomycin D treatment and RNase R digestion. Quantitative real-time PCR (qRT-PCR) was used to measure circRNA levels in clinical AML samples. The functional effects of hsa_circ_0001776 on proliferation and cell cycle progression were evaluated using the CCK-8 assay and flow cytometry. Bioinformatics analyses predicted putative miRNA interactions, which were validated by dual luciferase reporter assays. A p-value less than 0.05 was considered statistically significant.

hsa_circ_0001776 expression was significantly reduced in AML samples. Overexpression of hsa_circ_0001776 inhibited cell proliferation and induced G1 phase arrest in AML cells, whereas knockdown of hsa_circ_0001776 accelerated cell cycle progression and promoted malignant proliferation. hsa_circ_0001776 was shown to interact with miR-1269b, the pair being negatively correlated. PTEN was identified as a direct downstream target of miR-1269b, with complementary binding sites confirmed by luciferase assays.

hsa_circ_0001776 suppresses AML progression via the miR-1269b/PTEN axis. These findings suggest that hsa_circ_0001776 may serve as a potential diagnostic biomarker and therapeutic target for AML.