Mutation Screening in the Mitochondrial D-Loop Region of Tumoral and Non-tumoral Breast Cancer in Iranian Patients

The mitochondrial DNA (mtDNA) mutations in mitochondrial coding and non coding regions seem to be important in carcinogenesis. The aim of this investigation was to evaluate coding region (mt-tRNAPhe and tRNAPro) and non-coding sequence, mitochondrial displacement loop (mtDNA D-loop), in the cancerous and non-cancerous lesions of Iranian patients with breast cancer (BC). Genomic DNA was extracted from 50 breast tumors and surrounding normal tissue pairs as well as from 50 unrelated normal breast tissues from Iranian Kurdish population. Subsequently, PCR amplification was performed using specific primers, and then PCR products were subjected to direct sequencing. 41 genetic variants were identified in mtDNA D-loop among tumoral and non-tumoral tissues but not in tRNAPhe and tRNAPro sequences. Our findings indicated that C182T, 194insT, 285insA and 16342delT were just found in BC tumors whereas 302insC, C309T and C16069T found in both tumors and surrounding normal tissues. Although our findings showed that the observed genetic variations were not restricted to breast cancer tissues, some genetic changes were found only in BC tumors. Our results, in agreement with the evidence from earlier studies, confirm that the mtDNA genetic alterations might be implicated in tumor initiation, progression and development. text-align: justify

KIR3DL1 gene genotype in patients with spontaneous recurrent abortion

Introduction and objective: The mechanism of natural killer (NK) cells is based on the recognition of insider cells from alien cells according to inhibitory and activator responses of the receptor. One group of natural killer cell receptors are the killer immunoglobulin-like receptors (KIRs). It seems that decreased inhibitory activity or increased stimulatory activity of these receptors can play a key role in recurrent abortions. Thus, this study aimed to investigate the KIR3DL1 gene genotype in patients with spontaneous recurrent abortions due to its significance. Methodology: This case-control study was conducted on 40 patients with recurrent abortion, who were referred to Kamali Medical Center of Karaj in 2018 and 40 people with normal pregnancies. Genotypes of KIR genes were isolated using standard kits and two groups were compared in terms of KIR3DL1 genotype frequency. Data were analyzed through SPSS software using descriptive statistics (mean and standard deviation) and inferential statistics of paired t-test and Wilcoxon with a p-value less than 5%. Results: The KIR3DL1 genotype in the control group was found in 33 people (82.5%) and it was negative in 7 people (17.5%). The KIR3DL1 genotype in the case group was seen in 23 people (57.5%) and it was negative in 17 people (42.5) (p=0.012). The odds ratio (OR) was 0.287 with 95% confidence interval (0.102-0.802) and p= 0.0174. Conclusion: The results of this study revealed that the KIR3DL1 inhibitory genotype frequency was significantly lower in patients with recurrent abortion than that in those with normal pregnancy

Differential Expression of Human Homeodomain TGIFLX in Brain Tumor Cell Lines

Glioblastoma is the most common and the most lethal primary brain cancer. This malignancy is highly locally invasive, rarely metastatic and resistant to current therapies. Little is known about the distinct molecular biology of glioblastoma multiforme (GBM) in terms of initiation and progression. So far, several molecular mechanisms have been suggested to implicate in GBM development. Homeodomain (HD) transcription factors play central roles in the expression of genomic information in all known eukaryotes. The TGIFX homeobox gene was originally discovered in human adult testes. Our previous study showed implications of TGIFLX in prostate cancer and azoospermia, although the molecular mechanism by which TGIFLX acts is unknown. Moreover, studies reported that HD proteins are involved in normal and abnormal brain developments. We examined the expression pattern of TGIFLX in different human brain tumor cell lines including U87MG, A172, Daoy and 1321N1. Interestingly, real time RT-PCR and western blot analysis revealed a high level of TGIFLX expression in A172 cells but not in the other cell lines. We subsequently cloned the entire coding sequence of TGIFLX gene into the pEGFP-N1 vector, eukaryotic expression vector encoding eGFP, and transfected into the U-87 MG cell line. The TGIFLX-GFP expression was confirmed by real time RT-PCR and UV-microscopic analysis. Upon transfection into U87 cells, fusion protein TGIFLX-GFP was found to locate mainly in the nucleus. This is the first report to determine the nuclear localization of TGIFLX and evaluation of its expression level between different brain tumor cell lines. Our data also suggest that TGIFLX gene dysregulation could be involved in the pathogenesis of some human brain tumors