Abstract
Purpose: T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common malignancies associated with T-lymphocytes, accounting for 10 to 15 percent of ALL cases in children and 25 percent in adults. Innovative therapeutic approaches that overcome ineffective treatments on tumor cells may be a potential source of improvement in therapeutic approaches. Suppression of gene expression at transfusion level is one of the important strategies in gene therapy. The expression of PTPN22 and miR-181 genes in all types of hematologic malignancies increases and is likely to contribute to the survival and death of cells by affecting a variety of signaling pathways. The purpose of this study was to determine the role of PTPN22 inhibition by siRNA, and alteration in miR-181a and miR-181b in Jurkat cell line.Methods: Jurkat cells were transfected with 80 pmol of siRNA to inhibit PTPN22. After that, expression of PTPN22 mRNA and transcript levels of miR-181a and miR-181b were measured with Real-time PCR after 48hrs.Results: Experiments demonstrated that siRNA transfection resulted in significant downregulation of PTPN22 mRNA after 48 hrs in 80 pmol dose of siRNA. Moreover, transcript levels of both miR-181a and miR-181b was decreased after transfection.Conclusion: PTPN22, miR-181a and miR-181b might be involved in progression of Jurkat cells and targeting these molecules by RNAi might confer promising tool in treatment of T-ALL.
Highlights
T-cell acute lymphoblastic leukemia (T-ALL) is considered as one of the most frequent malignancies associated to T-cells, which is typically reflected as an invasive tumor.[1]
Results and Discussion siRNA downregulated PTPN22 mRNA in Jurkat cells The results showed that specific siRNA transfection downregulated significantly (P
At 48 hrs after transfection with 80 pmol of the specific siRNA molecule of PTPN22, the expression of PTPN22 was 23% (Figure 1).The results showed that highest reduction in expression level of the PTPN22 mRNA in Jurkat cells treated by specific siRNA was achieved at a dose of 80 pmol and 48 hours after transfection
Summary
T-cell acute lymphoblastic leukemia (T-ALL) is considered as one of the most frequent malignancies associated to T-cells, which is typically reflected as an invasive tumor.[1]. The physiological function of PTPN22 has been studied primarily in the context of T cells; it is not fully understood. PTPN22 is supposed to be located in the cytoplasm of T-cells and interacts with many signaling molecules, such as Lck, ZAP70, Csk, and Vav, thereby attenuating TCR signals.[8] Juxtaposition of promoter and enhancer components of TCR genes with transcription factor genes throughout VDJ recombination is among the cytogenetic changes inflicting T-ALL. Cytogenetic changes play a crucial role in leukemogenesis in cancers of immune cells together with T-ALL by altering the expression and function of miRNA, which may perform as tumor suppressors or oncogenes.[9] MicroRNAs (miRNAs) are single stranded ~22 nucleotides (nt) long non-coding RNAs that regulate gene expression at the post-transcriptional level. MiRNAs are encoded in host genes, which may be placed in introns or exons of protein-coding genes, as in non-coding genes.[10] miRNA restrictive roles in
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