Targeting MicroRNA Precursors in Acute Myeloid Leukemia: A System Biology Approach Using CRISPR/C۲c۲

Background:  Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by the rapid proliferation of immature myeloid cells in the bone marrow. This condition arises from genetic mutations in myeloid progenitor cells, leading to disrupted hematopoiesis and an accumulation of leukemic blasts in the bloodstream. Despite advances in treatment modalities, including chemotherapy and targeted therapies, clinical outcomes for AML patients remain suboptimal due to high rates of relapse and treatment resistance. Recent studies have identified specific microRNAs (miRNAs) that play critical roles in cancer metastasis and progression, suggesting that targeting these miRNAs could offer novel therapeutic avenues. The CRISPR-C۲c۲ system, a RNA-targeting gene editing tool, has emerged as a promising method for precisely modulating miRNA expression. By inhibiting oncogenic miRNAs or restoring tumor-suppressive miRNAs, this approach aims to mitigate AML progression. This study investigates the computational design of crRNAs targeting hsa-miR-۳۰۱b and hsa-miR-۲۱, both implicated in AML metastasis, utilizing bioinformatics tools to enhance targeting specificity and efficacy.  Methods: In this study mirBase server miRNA sequences were used to design crRNAs targeting AML metastasis. After that UALCAN server was used for expression analysis. Bioinformatics software, specifically the CRISPR-C۲c۲ system, was used for computational analysis. Structural studies were performed on the crRNAs, and simulation and molecular docking investigations were conducted to improve accuracy. Results: crRNAs targeting miR-۳۰۱b and miR-۲۱ exhibit significant structural resemblance with the binding energy seen in the healthy state. Conclusion: Evaluating crRNAs for RNA-level editing requires more than just sequence-based assessments; including simulation and molecular docking studies can enhance accuracy.

کلیدواژه ها:

AML ، miRNA ، CRISPR/C۲c۲ ، System Biology ، Precision Medicine