Study of microRNA Profile as a Molecular Biomarker in Egyptian Chronic Lymphocytic Leukemia

Abstract

MicroRNAs target mRNAs for cleavage or translational repression. They play a critical role in the progression of malignancies and leukemias including chronic lymphocytic leukemia (CLL). However, micro-RNA expression levels in Egyptian patients with CLL, and their prognostic value remain elusive. Our main aim was to assess the expression pattern of a panel of microRNAs in CLL patients to create an informative microRNA profile. The study subjects were 40 newly diagnosed CLL patients of both sexes and 40 age and sex matched controls. The expression levels of 12 microRNAs were evaluated by qRT-PCR, including miR-15a, 16, 23b, 24, 29a, 29c, 34a, 146a, 155, 181a, 195, and 221. Flow cytometry was used to determine the expression levels of BCL2, CD38, and ZAP-70 in CLL patients. We identified various degrees of upregulated miRNAs (miR-29a, miR-29c, miR-34a, miR-155, miR-146a, and miR-195) and down-regulated ones (miR-15a, miR-16, miR-23b, miR-24, miR-181a, and miR-221) in CLL patients relative to controls. The mean fluorescence intensity ratio (MFI-R) of BCL2 was recorded and was significantly upregulated in CLL patients compared with normal controls. In addition, inverse correlations were observed between microRNAs (miR-15a, miR-16, miR-155, and miR-195) and BCL2 MFI-R while positive correlations were observed between miR-29a and miR-29c, and BCL2 MFI-R. These findings suggest that these miR-NAs regulate BCL2 levels. Moreover, we found that miR-15a, miR-16, miR-155, miR-181a, miR-195 and miR-221 were significantly upregulated, while miR-29a and miR-29c were significantly downregulated in ZAP-70 positive CLL patients. Various miRNAs may play an important role in the pathogenesis of CLL and have the potential to be used for the prognosis of patients with CLL.

Inside the chronic lymphocytic leukemia cell: miRNA and chromosomal aberrations

“…The situation was similar in present study with miR-29a, whose expression was higher in ZAP-70-positive patients, despite previous evidence of reduced expression of this miRNA in ZAP-70-positive patients ( 49 ). Since a high percentage of ZAP-70-positive cells may indicate an aggressive course of CLL, and miRNA-221 is described as an oncomiR, it can be considered as a prognostic marker ( 23 ).…”

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia

“…MicroRNAs (miRNAs) are a group of small non-coding RNAs and play a crucial role in the regulation of gene expression. Human cancer is associated with miRNA expression, including CLL [ 81 – 83 ]. MiR-15a and miR-16-1, located on 13q14, were the earliest miRNAs used in the prognosis of CLL.…”

A Unified Computational Framework for a Robust, Reliable, and Reproducible Identification of Novel miRNAs From the RNA Sequencing Data

“…In comparison of dysregulated known miRNAs identified by miRDeep2, miRDeep*, miRPro, mirnovo, miRge2.0, sRNAToolbox, MiR&moRe2 and miRPipe with the literature, 17 out of 29 (58.62%), 18 out of 22 (81.81%), 21 out of 36 (58.33%), 14 out of 25 (56%), 8 out of 25 (32%), 2 out of 5 (40%), 2 out of 5 (40%) and 27 out of 31 (87.09%) miRNAs, respectively, were found to be reported as dysregulated in the literature of CLL. Here, the dysregulated miRNAs identified by miRPipe are found to be reported in multiple CLL-related literature ( Balatti et al, 2013 ; Shen et al, 2014 ; Ruiz-Lafuente et al, 2015 ; Balatti et al, 2016 ; Hu et al, 2018 ; Yang et al, 2018 ; Farahat et al, 2019 ; Gao et al, 2019 ; Farzadfard et al, 2020 ; Rahimi et al, 2021 ; Sitlinger et al, 2021 ). We have also reported 28 dysregulated piRNAs in CLL which, to the best of our knowledge, no one has reported till date.…”