| Background and Objective:Lymphoma is one of the most common malignant tumor which is harmful to human health and its incidence is increasing.Extranodal nasal type N K/T cell lymphoma(ENKTCL),which mainly occur in Asia and the central and southern America,is one of mature T and NK cell lymphoma subtypes,with an incidence of 5%-18% of non-hodgkin's lymphoma.It is a high-grade and aggressive malignancy with poor prognosis,and resistant to traditional chemotherapy.Early relapse of ENKTCL is common,and no standardized treatment for ENKTCL patients so far.It is necessary to further study the molecular mechanism of ENKTCL development and look for new therapeutic targets.According to the existing research,almost all cases of ENKTCL are associated with EBV infection,suggesting that EBV may take a crucial role on the oncogenesis of it.Yet the oncogenic mechanism of EBV in ENKTCL is underinvestigated.MicroRNAs encoded by EBV(EBV-miR)can mediate the mRNA expression of virus and host cells.MicroRNAs(miRNAs)are short sequences and non-coding protein RNAs,they may play key roles on cells' biology through degrading mRNA of target genes or inhibiting its translation.The dysregulation of miRNA can lead to the occurrence of many tumors,including lymphomas.EBV-miR-Bart6-3p has been confirmed to be abnormal expression in some tumors and involved in cell proliferation,apoptosis and so on.In the present study,the expression of EBV-miR-Bart6-3p in ENKTCL tissues and NK/T cell lymphoma(NKTCL)cells were tested by Quantitative Real-time PCR(qRT-PCR),the correlations between the EBV-miR-Bart6-3p expression level and clinicopathological featuresand prognostic significance of ENKTCL were analyzed,and the effects of EBV-miR-Bart6-3p on NKTCL cells proliferation and apoptosis were investigated.The goal of the study is to provide theoretical data for development of novel target therapies,which can cure ENKTCL.Methods:(1)qRT-PCR was used to detect the expression of EBV-miR-Bart6-3p in 42 cases of ENKTCL tissues and NKTCL cells.49 cases of nasopharyngeal mucosa benign lymphoproliferative lesions were used as the control group,twenty-seven of them were EBV-negative,others were EBV-positive.(2)The correlations between the expression level of EBV-miR-Bart6-3p and clinicopathological features and prognostic significance were analyzed.(3)EBV-miR-Bart6-3p mimic was transfected into NK/T cell lymphoma cell line,Jurkat cells.The cell proliferation was detected by CCK-8 assay,the cell cycle and apoptosis were detected by flow cytometry.Results:(1)The expression of EBV-miR-Bart6-3p in ENKTCL tissues group was significantly higher than EBV negative and EBV positive nasopharyngeal mucosa benign lymphoproliferative lesions groups(P < 0.01).The expression of EBV-miR-Bart6-3p in ENKTCL tissues was negatively correlated with B symptom and over all suvival(P<0.05).The elevated level of serum LDH,increased IPI score,abnormal blood routine and abnormal liver function were related to poor prognosis in patients with ENKTCL.(2)The expression of EBV-miR-Bart6-3p in miRNA transfection group was significantly higher than those in negative control group(P < 0.01).(3)The proliferational rate of NKTCL cells with EBV-miR-Bart6-3p expression was significantly increase at 24 h,48 h,72 h and 96 h after transfection,when compared with those in control group(P < 0.05).(4)Compared with the negative control group,the overexpression of EBV-miR-Bart6-3p could inhibit the apoptosis of NKTCL cells(P < 0.05).But there was no significant difference in the proportion of cells in each phase of cell cycle among the two groups(P > 0.05).Conclusion:(1)EBV-miR-Bart6-3p is overexpressed in ENKTCL tissues and NKTCL cells.(2)The expression of EBV-miR-Bart6-3p is negative correlated with the overallsurvival rate of ENKTCL patients.(3)EBV-miR-Bart6-3p may contribute to the development of ENKTCL by promoting NK/T cell proliferation,while inhibiting cell apoptosis. |
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