<p>Serum Expression of Seven MicroRNAs in Chronic Lymphocytic Leukemia Patients</p>

Abstract

Purpose: MicroRNAs are small single-strand noncoding RNAs that can be deregulated in a variety of cancers. Over the past few years, multiple markers have been discovered in chronic lymphocytic leukemia (CLL). Among these, miRNAs seem to have important roles in the pathogenesis of CLL. The development and validation of miRNA-expression patterns as biomarkers should have a significant impact in cancer diagnosis, therapeutic success, and increasing the life expectancy of patients. In this study, to specify the utility of circulatory miRNA expression as noninvasive and useful biomarkers for CLL, we analyzed the dysregulation of seven miRNAs: miR30d, miR25-3p, miR19a-3p, miR133b, miR451a, miR145, and miR144 in CLL-patient sera. Methods: Thirty untreated patients with flow-cytometry confirmation of CLL were chosen. Serum samples were collected from 30 newly diagnosed CLL patients. Fifteen healthy samples were taken for comparison as controls. RNA was extracted using Trizol. RNA from CLL patient specimens was compared to controls with real-time PCR. Results: Seven miRNAs were differently expressed between CLL and normal specimens using the comparative 2 −ΔΔ Ct method. miRNAs 133b, 25-3p, 451a, 145, 19a-3p, and 144 were overexpressed in sera obtained from CLL patients, and miRNA-30d was underexpressed in patient samples. Among these seven miRNAs, miR19a-3p and miR25-3p showed the most deregulation in CLL patients. Conclusion: Real-time PCR is an applied means to perform high-throughput investigation of serum-RNA samples. We assessed the expression of seven miRNAs in CLL patients by this method. The results demonstrated that the use of miRNA-expression profiling may have an impressive role in the diagnosis of CLL. In addition, miRNA 19a-3p and 25-3p are known oncogenes with therapeutic and potential biomarkers.

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.…”

Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia

“…That is in agreement with the results of Selven et al who showed a favorable prognosis for colorectal cancer patients with high miR-20a-5p expression [ 33 ]. Similarly, Farzadfard et al reported higher circulating miR-19a-3p in CLL patients than in healthy subjects [ 2 ]. Moreover, Khalifa et al showed significant overexpression of all miR-17∼92 cluster members in CLL patients in comparison to the control group [ 34 ].…”

“…CLL displays a heterogeneous spectrum of biological features and clinical manifestations. Due to clinical interindividual heterogeneity of CLL cases, identification of prognostic factors is of great importance in both predicting the course of the disease as well as selecting the optimal therapy [ 1 , 2 , 3 , 4 ].…”

“…The most clinically significant markers of poor disease outcome are the lack of mutations in the immunoglobulin heavy chain variable region locus ( IGHV ), deletion of chromosome 11q or 17p, as well as high expression of ZAP-70 (zeta-associated protein 70) and CD38 [ 1 , 2 , 3 ]. Moreover, recurrent genetic abnormalities, such as TP53 , ATM , NOTCH1 , SF3B1 , BIRC3 , and MYD88 mutations are associated with disease prognosis, and some of them may influence treatment decisions [ 3 , 5 , 6 ].…”

Exosome application in treatment and diagnosis of B-cell disorders: leukemias, multiple sclerosis, and arthritis rheumatoid

“…- decreasing in the intracellular level of this miRNA causes an increase in the expression level of Sufu, which aids tumor cell survival and progression. Oncogene [ 69 , 71 ] miR-146a/miR-451 Upregulated Kinases in Stromal cells inducing the stromal cells activation by phosphorylation of several kinases Oncogene [ 69 , 71 , 75 ] miR-150 Upregulated c-Myb playing an important role in the process of hematopoiesis, particularly in the development of lymphoid lineage Oncogene [ 69 , 71 ] miR-19b Upregulated TP53 and MKI67 TP53 downregulation and MKI67 upregulation as tumor cell proliferation, survival, and invasion mechanisms Oncogene [ 69 , 76 ] miR-155 Upregulated SHIP1 In CLL, it has an oncogenic role; it promotes the BCR response by targeting SHIP1. Oncogene [ 69 , 71 ] miR-29 Downregulated TCL1 regulation of TCL1, MCL1 and DNA-methyltransferases Tumor suppressor function in aggressive CLLs (downregulated versus indolent CLL) [ 69 , 71 ] miR-223 Downregulated HSPs HSP90B1 Oncogene [ 69 , 77 , …”