Circulating lncRNA HOTAIR is a biomarker for pediatric acute lymphoblastic leukemia and mediator of miR-326 exosomal...

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children worldwide. In the present investigation, the circulating RNAs (circRNAs) HOTAIR, NEAT1, H19, PCAT1, and SNHG1 were selected as potential biomarkers for childhood ALL (pALL) based on their predicted interactions with miR-326, a recognized tumor suppressor implicated in pALL, along with comprehensive in silico analyses. Subsequently, the expression levels of the circRNAs were examined in 50 pALL samples and 20 healthy controls using RT-qPCR. Notably, HOTAIR was identified as a 95% specific biomarker of cancer susceptibility, exhibiting a substantial increase in expression within the bone marrow plasma and peripheral blood samples. 22 B-ALL patients with elevated relative expression levels of circHOTAIR (≥ 1.87) were then monitored at three distinct time intervals during chemotherapy. Results demonstrated a significant decrease in HOTAIR expression only among treatment-sensitive patients (P < 0.0001). This finding positions HOTAIR as a novel prognostic factor (AUC = 0.955), which may be used for monitoring the efficacy of chemotherapy in a non-invasive, cost-effective manner. Additionally, the regulatory inter-connection between HOTAIR and miR-326 was investigated by transfecting B-ALL RN-95 cells with exogenous miR-326. Data showed a time-dependent increase in cytoplasmic HOTAIR levels, alongside RAB35, resulting in a corresponding reduction in the cytoplasmic and exosomal miR-326 levels. While the results are preliminary due to the sample size, this study is the first to identify circHOTAIR as both a prognostic and diagnostic biomarker in B-ALL. Furthermore, it elucidates the role of HOTAIR as a sponge for miR-326, orchestrating its efflux from the cell via exosomes through RAB35.