miR-19b (miR-19b-3p) has been reported to be correlated with either favorable or unfavorable events in several cancers. However, no study has been conducted to evaluate the expression level of miR-19b in patients with breast cancer (BC). This study was aimed to investigate the expression level of miR-19b in human malignant and healthy breast tissues with histopathology of ER+/PR+/HER2-. We performed a miRNA real-time PCR to detect differential expression of miR-19b in 40 BC, including 17 BC with familial background and 23 BC without familial background, and 12 non-tumoral tissues. Moreover, a bioinformatics prediction upon miR-19b functionality in BC cells was performed. The miR-19b expression level was significantly down-regulated in BC, BC with familial background, and BC without familial background compared with its expression in normal tissue (p value, <0.0001; fold change, -7.45; p value, 0.0003; fold change, -6.45; and p value, 0.0005; fold change, -8.41, respectively). Moreover, according to the AUCs (area under curve) of receiver operating characteristic (ROC) curves, miR-19b can significantly distinguish all defined categories. Last, in agreement with our experimental findings, proteoglycans in cancer, pathways in cancer, FoxO signaling pathway, central carbon metabolism in cancer, p53 signaling pathway, transcriptional misregulation in cancer, and prolactin signaling pathway were predicted as miR-19b-related signaling pathways. In summary, down-regulation of miR-19b in BC vs healthy tissue suggests that mir-19b can function as a tumor suppressor. Our results shed additional information on controversial expression pattern of miR-19b depending on different cancer types.
Background:Cytokine gene single nucleotide polymorphisms (SNPs) are widely used to study susceptibility to complex diseases and as a tool for anthropological studies.Materials and Methods:To investigate cytokine SNPs in an Iranian multi-ethnic population, we have investigated 10 interleukin (IL) SNPs (IL-1β (C-511T, T-31C), IL-2 (G-384T), IL-4 (C-590T), IL-6 (G-174C), IL-8 (T-251A), IL-10 (G-1082A, C-819T, C-592A) and tumor necrosis factor-alpha (TNF-α) (G-308A) in 415 Iranian subjects comprising of 6 different ethnicities. Allelic and genotypic frequencies as well as Hardy-Weinberg equilibrium (HWE) were calculated by PyPop software. Population genetic indices including observed heterozygosity (Ho), expected heterozygosity (He), fixation index (FIS), the effective number of alleles (Ne) and polymorphism information content (PIC) were derived using Popgene 32 software. Multidimensional scaling (MDS) was constructed using Reynold's genetic distance obtained from the frequencies of cytokine gene polymorphism.Results:Genotypic distributions were consistent with the HWE assumptions, except for 3 loci (IL-4-590, IL-8-251 and IL-10-819) in Fars and 4 loci (IL-4-590, IL-6-174, IL-10-1082 and TNF-α-308) in Turks. Pairwise assessment of allelic frequencies, detected differences at the IL-4-590 locus in Gilakis versus Kurds (P = 0.028) and Lurs (P = 0.022). Mazanis and Gilakis displayed the highest (Ho= 0.50 ± 0.24) and lowest (Ho= 0.34 ± 0.16) mean observed heterozygosity, respectively.Conclusions:MDS analysis of our study population, in comparison with others, revealed that Iranian ethnicities except Kurds and Mazanis were tightly located within a single cluster with closest genetic affinity to Europeans.
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