The impact of variations in transcription of DICER and AGO2 on exacerbation of childhood B‐cell lineage acute lymphoblastic leukaemia

• Published in: International journal of experimental pathology Vol. 100; no. 3; pp. 184 - 191
• Main Authors: Piroozian, Fatemeh, Bagheri Varkiyani, Hoda, Koolivand, Mohsen, Ansari, Maryam, Afsa, Masoomeh, AtashAbParvar, Ali, MalekZadeh, Kianoosh
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2019; John Wiley and Sons Inc
• Subjects: acute lymphoblastic leukaemia; Acute lymphoblastic leukemia; Adolescent; AGO2; Argonaute 2 protein; Argonaute Proteins - metabolism; B-Lymphocytes - cytology; Biosynthesis; Cell lineage; Cell Lineage - immunology; Child; Child, Preschool; Children; Cytoplasm; DEAD-box RNA Helicases - metabolism; DICER; Disease Progression; Female; Genes; Humans; Leukemia; Lymphocytes B; Male; Malignancy; microRNA biogenesis; MicroRNAs; MicroRNAs - genetics; miRNA; Original; Pathogenesis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Real-Time Polymerase Chain Reaction - methods; Ribonuclease III - metabolism; Ribonucleic acid; RNA; Transcription; microRNA biogenesis; DICER; acute lymphoblastic leukaemia; AGO2
• ISSN: 0959-9673; 1365-2613; 1365-2613
• DOI: 10.1111/iep.12316

Summary The expression of microRNA in eukaryotic cells is subject to tightly regulated processing. The altered expression of microRNAs in a number of cancers suggests their contribution to disease pathogenesis, where processing pathways may be involved in disease pathogenesis. In the present study, we evaluated changes in the profile of two main components of microRNA biogenesis, AGO2 and DICER, and assessed their correlation with disease progression in childhood acute lymphoblastic leukaemia (ALL). To achieve this aim, 25 patients afflicted with ALL were included in the study along with 25 healthy subjects as control. The expression level of AGO2 and DICER was evaluated by real‐time PCR. The results revealed an increase in the expression of DICER and a decrease in AGO2 in patients. The correlation between the alteration levels of these genes with pathologic events was also studied. This increase or decrease proved to be directly correlated with the progression of the disease particularly in L1 to L2. According to the obtained results, it can be deduced that dysregulation in transcription of DICER and AGO2, involved in the formation of mature microRNAs in cytoplasm of ALL cancer cells, is a part of the pathological molecular mechanism implicated in the exacerbation of this malignancy. Therefore, the genes involved in microRNAs biogenesis that have been studied here could be considered as candidate prognostic markers especially in childhood ALL which will help towards a better understanding of the molecular basis of ALL.