Aberrant expression profile of miR-32, miR-98 and miR-374 in chronic lymphocytic leukemia
Zohreh Rahimi1, Zahra Ghorbani2, Hajar Motamed3
1Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Introduction:
Leukemia is a malignant and progressive disease of hematopoiesis. The disease arises due to abnormal proliferation and development of white blood cells and their precursors in the blood and bone marrow. Chronic lymphoblastic leukemia (CLL) is a subtype of blood cancers, with the origin of B lymphocytes and the involvement of bone marrow, blood and lymph nodes. MicroRNAs (miRNAs) are small non-coding RNAs with pivotal roles in cellular and molecular processes related to different malignancies, including CLL. In this way, we aimed to evaluate the expression of miR-32-5p, miR-98-5p, and miR-374b-5p in CLL patients. We also investigated the signaling pathways regulated by the studied miRs and also frequently disturbed miRs in CLL.
Methods:
Blood samples were collected from 32 CLL patients from Kermanshah province, Iran and 34 age and sex-matched healthy individuals. RNA was extracted from PBMCs and then was subjected to cDNA synthesis. Using specifically designed primers and Real-Time PCR method the expression of miRNAs was detected and was statistically analyzed. Using mirPath v.3, systematic pathway enrichment analysis was performed for the three studied miRNAs here along with the frequently disturbed miRNAs in CLL.
Results:
The experiments indicated a significant reduction in the expression of all three miRs (p-value<0.0001) in CLL patients compared with healthy individuals. ROC analysis suggested that the three studied miRs can serve as potential biomarkers for early diagnosis of CLL. The in silico analysis suggested proteoglycans in cancer as a pathway regulated by the studied miRs and frequently dysregulated miRs in CLL.
Conclusion:
The observed reduction in expression of miR-32-5p, miR-98-5p, and miR-374b-5p in treatment naïve CLL patients here might be suggestive of their modulatory protective role in CLL progression. Moreover, the candidate peripheral miRNAs could potentially serve as diagnostic biomarkers which warrant further investigation in a larger sample size.
