HOTAIR promotes the progression of B-cell acute lymphoblastic leukemia by regulating the miR-326/IGF-1R axis and activating the PI3K/AKT signaling pathway.

BACKGROUND

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy. Long non-coding RNAs (lncRNAs) play important roles in hematological diseases; nevertheless, their mechanistic contributions to B-ALL are still poorly defined.

PURPOSE: This study aimed to investigate the oncogenic role of HOTAIR and the regulatory mechanism underlying the progression of B-ALL via the HOTAIR/miR-326/IGF-1R axis.

METHODS

The expression levels of HOTAIR and miR-326 were quantified by RT-qPCR in peripheral blood mononuclear cells (PBMCs) from B-ALL patients. CCK-8, EdU, and TUNEL assays were employed to evaluate cell viability, proliferation, and apoptosis, respectively. Dual-luciferase reporter assays were performed to verify molecular interactions, and Western blotting was performed to detect the activation of the PI3K/AKT signaling pathway.

RESULTS

HOTAIR was prominently upregulated in patient-derived PBMCs, correlating with enhanced proliferation and suppressed apoptosis. Mechanistically, HOTAIR directly targeted miR-326 binding sites and regulated the expression of IGF-1R. Experiments affirmed that overexpression of miR-326 or knockdown of IGF-1R reversed the oncogenic effects induced by HOTAIR. Furthermore, silencing of HOTAIR decreased PI3K/AKT phosphorylation, indicating pathway dependence.

CONCLUSION

HOTAIR promotes the progression of B-ALL via the miR-326/IGF-1R axis and PI3K/AKT activation, suggesting its potential as a therapeutic target.