Expression and clinical significances of miR-215 and RUNX1 in retinoblastoma / 中国医师杂志

Objective To investigate the expression and clinical significances of miR-215 and runtrelated protein1 (RUNX1) in retinoblastoma (RB),and to study the regulation effect of miR-215 on RUNX1 in the retinoblastoma cell line PMC-RB.Methods The expressions of miR-215 and RUNX1 in the tumor tissue,non tumor tissues adjacent to cancer,human RB cell line FMC-RB and human normal retinal vascular endothelial cell line ATCC of RB patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR).miR-215 mimics (miR-215-mimic),miR-NC,si-RUNX1 and si-NC were transfected into FMC-RB cell line respectively.Cell proliferation,migration and invasion ability were measured respectively,thus detecting the regulation effect of miR-215 on RUNX1.Results The expression of miR-215 in RB tissues was significantly lower than that in non tumor tissues adjacent to cancer,while the mRNA expression of RUNX1 was higher than that in non tumor tissues adjacent to cancer (P ＜ 0.05).The expression of miR-215 in PMC-RB cells was lower than that in ATCC,while the mRNA expression of RUNX1 was higher than that in ATCC (P ＜0.05).The expression of miR-215 and RUNX1 in RB tumor tissues were closely related to the clinicopathological features of optic nerve infiltration,tumor tissue differentiation and lymph node metastasis (P ＜ 0.05).Cell proliferation,migration and invasion in miR-215-mimic group were significantly lower than those in miR-NC group (P ＜ 0.05).In transfected 3' untranslated region (3 'UTR)-Wt cells,the luciferase activity in miR-215-mimic group was lower than that in miR-NC group (P ＜ 0.05);the expression level of RUNX1 protein in transfected miR-215-mimic cells was lower than that in transfected miR-NC cells (P ＜ 0.05).Cell proliferation,migration and invasion in si-RUNX1 group were all lower than those in si-NC group (P ＜ 0.05).There was a negative correlation between mRNA expression level of miR-215 and RUNX1 in RB tumor tissues.Conclusions During the occurrence and development of RB,the down-regulation of miR-215 expression can promote malignant progression of tumor by targeting RUNX1.miR-215 can be used as a biological markers and therapeutic target for RB diagnosis.

Haematological & molecular profile of acute myelogenous leukaemia in India.

Background & objectives: Recurrent balanced translocations are generally recognized to be a major parameter for prognostication in acute myeloid leukaemia (AML). The chromosomal translocation t(15;17) results in PML/RARα fusion gene, t(8;21) results in AML1/ETO fusion gene and Inv 16 generates CBFβ/MYH11 fusion gene. Patients with these mutations have a good prognosis unlike abnormalities in chromosome 5 or 7 or FLT3 genes. Therefore, we screened the AmL patients for known specific genetic abnormalities that could lead to more definitive prognoses. Methods: A total of 113 AML patients were evaluated at diagnosis based on routine morphology and cytochemistry and classified according to the WHO criteria. The distribution of AML subtypes was M1(1), M2(32), M3(57), M4(14), M5(1), M6(1) and seven cases where morphological subtype could not be classified. RT-PCR was performed to identify PML/RARα, AML1/ETO, CBFβ/MYH11 and FLT3 internal tandem duplication (ITD). Results: Of the 57 patients with M3 subtype, 55 had the PML-RARα fusion transcript. The prevalence of bcr3 (short isoform) was higher (62%) than that of bcr1 (long isoform) (38%) and no correlation was found with age, sex or white blood cell count. FLT3 internal tandem duplication (ITD) mutations were more frequent in patients with APL than in other AML subtypes (17.5 vs. 8.9%), the frequency greater in patients with bcr3 isoform (70%) than in those with in bcr1 isoform (30%). Patients with FLT3/ITD mutations had a significantly higher median white cell count than those without these mutations (55 x 109/l vs. 6.3 x 109/l; P<0.001). More patients with FLT3/ITD mutations died early (53%) than those without these mutations (16%) (P<0.01). AML1-ETO fusion transcript was detected in 16 of 56 patients with no correlation with clinical or haematological parameters. Interpretation & conclusion: The results of the present study showed presence of bcr3 (short isoform) higher than bcr1 (long isoform). FLT3 internal tandem duplication (ITD) mutation was predominant in acute promyelocytic leukaemia patients with bcr3 isoform. Thus, patients with APL who have FLT3 mutation appear to have a poorer prognosis. Therefore, rapid identification of specific translocations at diagnosis is important for prognostic purposes and their detection should be incorporated into routine assessment.

Putative association of RUNX1 polymorphisms with IgE levels in a Korean population

RUNX1, a member of the runt domain gene family of transcription factors, encodes a heterodimeric transcription factor and regulates the expression of various genes related to hematopoiesis and myeloid differentiation. RUNX1 has been one of the target genes for research into various autoimmune diseases due to its properties as a transcription factor and functional distribution for chromosomal translocation. In an effort to identify additional gene polymorphisms in which variants have been implicated in asthma, we investigated the genetic polymorphisms in RUNX1 to evaluate it as a potential candidate gene for a host genetic study of asthma and IgE production. We identified 19 sequence variants by direct DNA sequencing in 24 individuals of which four common variants were selected for genotyping in our asthma cohort (1,055 asthmatic patients, 384 normal controls). Using logistic regression analysis for association with the risk of asthma, while controlling for age, gender, and smoking status as covariates, no significant associations with the risk of asthma were detected. However, two polymorphisms in the promoter region (-2084G>C and -1282G>A) showed a marginal association with total IgE levels (0.03 and 0.03 in recessive models, respectively). Our findings suggest that polymorphisms in RUNX1 might be one of the genetic factors for the regulation of IgE production.