Diagnostic Value of Plasma miR-145 and miR-185 as Targeting of the APRIL Oncogene in the B-cell Chronic Lymphocytic Leukemia.

Malihe Bagheri,Mahdieh Mondanizadeh,Ghasem Mosayebi,Behzad Khansarinejad,Alireza Moradabadi

doi:10.31557/apjcp.2021.22.1.111

Malihe Bagheri, Mahdieh Mondanizadeh + Show 3 more

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https://doi.org/10.31557/apjcp.2021.22.1.111

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Abstract

Background:Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancy in adults worldwide. This cancer has a poor prognosis at different stages. So, the identification of new biomarkers is important for diagnosis of B-CLL. Considering the oncogenic role of APRIL molecule in this leukemia as well as the regulatory role of miRNAs in different signaling pathways, the present study evaluated the miRNAs targeting APRIL gene in B-CLL.Methods:The miRNAs were predicted and selected using bioinformatics algorithms. A total of 80 plasma samples were subjected to RNA extraction and synthesis of cDNA. The expressions levels of predicted miRNAs and APRIL gene in plasma of B-CLL patients and healthy individuals were assessed by Real time PCR analysis. ROC analysis was performed to investigate the role predicted miRNAs as novel biomarkers in diagnosis of B-CLL.Results:The results of the prediction showed that miR-145-5p and miR-185-5p target the APRIL gene. The expression level of APRIL gene was strikingly higher in plasma of B-CLL patients than in the healthy individuals (102, P= 0.001). On the other hand, expression levels of miR-145-5p and miR-185-5p were strikingly lower in B-CLL patients than in the healthy individuals (0.07, P= 0.001) (0.29, P= 0.001). Also, ROC curve analyses demonstrated that miR-145-5p and miR-185-5p are specific and sensitive and may serve as new biomarkers for the detection of B-CLL. (AUC; 0.95, sensitivity; %90) (AUC; 0.87, sensitivity; %63). Conclusion:These data suggest that miR-145-5p and miR-185-5p target the APRIL gene and might have a role in diagnosis of B-CLL. Therefore, these two miRNAs can be served as a novel and potential biomarker for detection of B-CLL.

Highlights

Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancy in adults worldwide, that makes up approximately 30% of all blood cancers (Rodrigues et al, 2016)
In diagnosed of B-CLL patients, European Group for the Immunological Characterization of Leukemias (EGIL) suggested the flow cytometry marker to diagnosed positive for CD5, CD19, CD20 and CD23, the level of surface CD20, and CD79 are low in compare of normal B-cell B-cells are negative for CD13, CD117 and other myeloid linage markers
The identification of new biomarkers with high sensitivity and specificity is crucial for early diagnosis of B-CLL

Summary

Introduction

Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancy in adults worldwide, that makes up approximately 30% of all blood cancers (Rodrigues et al, 2016). MicroRNAs (miRNAs) with properties such as tissue specificity, rapid release rate and plasma stability have been identified as non-invasive biomarkers in diagnosis and treatment of CLL (Mitchell et al, 2008; Moussay et al, 2011; Wang et al, 2017). These molecules regulate gene expression through target mRNA degradation or inhibition in translation level (Mirzaei et al, 2018b). Considering the role of APRIL molecule in the pathogenesis of CLL and the regulatory role of miRNAs in many signaling pathways, the aim of present study was to identify miRNAs targeting APRIL mRNAs in B-CLL

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Discussion