Soltani Ismael, Bahia Wael, Farrah Ahlem, Mahdhi Abdelkarim, Ferchichi Salima, Almawi Wassim Y
Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Université Tunis El Manar, Tunis, Tunisia.
Research unit of clinical and molecular biology, Department of biochemistry, Faculty of Pharmacy of Monastir, University of Monastir, Tunisia.
Genomics. 2021 Jul;113(4):1647-1658. doi: 10.1016/j.ygeno.2021.04.014. Epub 2021 Apr 20.
Considering the critical roles of hsa-miR-155-5p participated in hematopoietic system, this study aims to clarify the possible pathogenesis of chronic myeloid leukemia (CML) induced by hsa-miR-155-5p.Three different strategies were employed, namely a network-based pipeline, a survival analysis and genetic screening method, and a simulation modeling approach, to assess the oncogenic role of hsa-miR-155-5p in CML. We identified new potential roles of hsa-miR-155-5p in CML, involving the BCR/ABL-mediated leukemogenesis through MAPK signaling. Several promising targets including E2F2, KRAS and FLI1 were screened as candidate diagnostic marker genes. The survival analysis revealed that mRNA expression of E2F2, KRAS and FLI1 was negatively correlated with hsa-miR-155-5p and these targets were significantly associated with poor overall survival. Furthermore, an overlap between CML-related genes and hsa-miR-155-5p target genes was revealed using competing endogenous RNA (ceRNA) networks analysis. Taken together, our results reveal the dynamic regulatory aspect of hsa-miR-155-5p as potential player in CML pathogenesis.
鉴于hsa-miR-155-5p在造血系统中发挥的关键作用,本研究旨在阐明由hsa-miR-155-5p诱导的慢性髓性白血病(CML)的可能发病机制。采用了三种不同的策略,即基于网络的流程、生存分析和基因筛选方法以及模拟建模方法,来评估hsa-miR-155-5p在CML中的致癌作用。我们确定了hsa-miR-155-5p在CML中的新潜在作用,包括通过MAPK信号通路介导的BCR/ABL白血病发生。筛选出了几个有前景的靶点,包括E2F2、KRAS和FLI1,作为候选诊断标记基因。生存分析显示,E2F2、KRAS和FLI1的mRNA表达与hsa-miR-155-5p呈负相关,并且这些靶点与总体生存率差显著相关。此外,使用竞争性内源RNA(ceRNA)网络分析揭示了CML相关基因与hsa-miR-155-5p靶基因之间的重叠。综上所述,我们的结果揭示了hsa-miR-155-5p作为CML发病机制中潜在参与者的动态调节方面。