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The efficacy of statins as anti-cancer drugs has been demonstrated in several malignancies but has been poorly investigated in hematological malignancies (HM). By studying its effect on oncogenic miRNAs, we investigated the effect of statin therapy on HM patients. The data were used to identify enriched pathways that were altered due to statin treatment. The main aim of this study was to identify significantly differentially expressed miRNAs and involved regulatory pathways post-atorvastatin treatment in HM patients. A panel of 95 plasma circulating miRNAs involved in tumorigenesis, apoptosis, and differentiation were relatively quantified using qPCR for blood samples obtained from 12 HM patients, 4 with Chronic Myeloid Leukemia (CML), 4 with Non-Hodgkin Lymphoma (NHL), and 4 with Essential Thrombocythemia. Pre- and post-administration of a 6-week atorvastatin course miRNA expression levels were measured. Significantly differentially expressed miRNAs were those with a fold change >2 or <0.5 using the Livak method with a two-sided p-value < 0.05. To further understand the underlying mechanism of statin regulated miRNA, GO and KEGG pathway enrichment analyses were conducted for identified target genes using the DAVID 6.8 bioinformatics tool. Out of 95 miRNAs, 14 exhibited significant fold changes post-treatment with statins including miR-198, miR-29a+b+c, miR-204, miR-222, miR-224, miR-155, miR-128b, miR-296, miR-199a+b, miR-194, miR-125a, miR-200a, and the let-7-family that were upregulated and miR-150 that was downregulated post-statin treatment. Higher mir-222, mir-194, mir-128b, and mir-199b expressions were significantly associated with better overall survival using the Cancer Genomic Atlas leukemia and lymphoma patient cohorts. Enrichment analysis identified the PI3k-Akt pathway as well as other pathways involved in the epithelial–mesenchymal transition. Atorvastatin upregulated several tumor suppressor genes involved in mediating better prognosis. The data can be used to enhance personalized treatments for patients with hematological malignancies by helping to predict the different pathways that may be targeted and, therefore, result in better survival outcomes in these patients. [ABSTRACT FROM AUTHOR]

The dysregulation of miRNA expression has been shown to impact cellular physiology and tumorigenesis. Studies have reported several miRNA regulatory elements and pathways that play a significant role in the diagnosis, prognosis, and treatment of hematological malignancies. This is the first study to test the differential expression of miRNAs at crucial stages of the disease, specifically newly diagnosed, resistant to treatment, and remission. Circulating miRNAs extracted from the blood samples of 18 patients diagnosed with leukemia or lymphoma at different stages and 2 healthy controls were quantified by qPCR using a panel of 96 tumorigenic miRNAs. An enrichment analysis was performed to understand the mechanisms through which differential miRNA expression affects cellular and molecular functions. Significant upregulation of hsa-miR-1, hsa-miR-20a-5p, hsa-miR-23a-3p, hsa-miR-92b3p, and hsa-miR-196a-5p was detected among the different stages of leukemia and lymphoma. mir-1 and mir-196a-5p were upregulated in the remission stage of leukemia, while mir-20a-5p, mir-23a-3p, and mir-92b-3p were upregulated during the resistant stage of lymphoma. The enrichment analysis revealed these miRNAs' involvement in the RAS signaling pathway, TGF-β signaling, and apoptotic pathways, among others. This study highlights new biomarkers that could be used as potential targets for disease diagnosis, prognosis, and treatment, therefore enhancing personalized treatments and survival outcomes for patients. [ABSTRACT FROM AUTHOR]