CML-553 Statin's Effect on Oncogenic miRNAs in Hematologic Malignancy Patients

Abstract

The effect of statins in cancer management has been demonstrated in several malignancies but poorly investigated in hematologic malignancies (HM). We investigated the effect of statins on HM patients, by studying its effect on oncogenic miRNAs. To identify significantly differentially expressed miRNAs and involved regulatory pathways post atorvastatin treatment in HM patients. Interventional study. From 2018 to 2020. University Hospital. 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, 4 with non-Hodgkin lymphoma, 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 differentially GO and KEGG pathway enrichment analyses were conducted for identified target genes using the DAVID 6.8 bioinformatics tool. Out of 95, 14 miRNAs 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 epithelial-mesenchymal transition. Atorvastatin upregulated several tumor suppressor genes involved in mediating better prognosis. These findings provide deeper insight on statin's effect on the transcriptional regulatory level in cancer which can be used to enhance personalized treatment options for HM patients. Further studies on larger homogeneous samples are needed to confirm the long-term effects of adding statins to HM standard lines of therapy.