Association and in silico investigations of miR-302c insertion/deletion variant as a novel biomarker with susceptibility to gastric cancer.

Gastric cancer (GC) is the fifth most prevalent malignant tumor and the third most frequent cause of cancer mortality worldwide. rs199971565 is an insertion/deletion (INDEL) located in microRNA-302c (miR-302c) seed site, which may affect its function and biogenesis. There is no genetic association study investigating this INDEL with any disease till now. Thus, the current study was conducted to investigate the association of rs199971565 with susceptibility to GC in an Iranian population. In addition, in silico studies were performed to reveal the possible functional significance of this INDEL. A total of 378 subjects were genotyped through amplification refractory mutation system PCR (ARMS-PCR) after DNA extraction from peripheral blood by the salting out procedure. Also, in silico analyses were performed through databases and web tools including MiRNASNP V2.0, miRWalk V2.0, miRTarBase, DAVID V6.8, RNAfold, PHDcleave, miRmap, and STarMir. Results revealed that there was an association between rs199971565 and the incidence risk of GC under a recessive (P = .04, odds ratio [OR] = 18.73; 95% confidence interval [CI] = 1.07-326.95) model of inheritance. Also, compared to the Ins allele, the Del allele significantly increased the risk of GC (P = .01, OR = 2.02; 95% CI = 1.11-3.66). Further analyses showed no significant association in age and sex between two study groups (P = .216 and P = .798, respectively). In conclusion, for the first time, this study indicated the association and in silico investigations of rs199971565 and suggested it as a novel INDEL biomarker located in the seed site of miR-302c, which may have crucial roles in the susceptibility to GC and its incidence risk.

The role of epigenetics in the induction of fetal hemoglobin: a combination therapy approach.

BACKGROUND: ß-thalassemia considers worldwide public health disorders. Novel fetal hemoglobin inducer agents such as thalidomide and sodium butyrate have been attended for ameliorating clinical complications of such disorders. MATERIAL AND METHODS: We used thalidomide and sodium butyrate for increasing the level of fetal hemoglobin in erythroid progenitors. Briefly, after isolation of CD133+ stem cells from umbilical cord blood and differentiation into erythroid lineage, erythroid progenitors were treated with thalidomide and sodium butyraye as single and combination. H3K4 histone methylation was evaluated following fetal hemoglobin induction using chromatin immuno percipitation (ChIP) technique. RESULTS: The results of this study showed that the effect of thalidomide on increasing of H3K4 methylation was highest compared to sodium butyrate and combination of both agents (p < 0.05). CONCLUSION: Consequently, our study of the epigenetic modification of the γ-globin suggests that histone H3K4 dimethylation are significant for the regulation of developmental stage-specific expression of the γ-globin genes.