Integrins are adhesion molecules which play crucial roles in cell-cell and cell-extracellular matrix interactions. Very late antigen-4 or α4β1 and lymphocyte Peyer’s patch adhesion molecule-1 or α4β7, are key factors in the invasion of tumor cells and metastasis. Based on the previous reports, integrin α4 (ITGA4) is overexpressed in some immune disorders and cancers. Thus, inhibition of ITGA4 could be a therapeutic strategy. In the present study, miR-30a was selected in order to suppress ITGA4 expression. The ITGA4 3' UTR was amplified, cloned in the Z2827-M67-(ITGA4) plasmid and named as Z2827-M67/3'UTR. HeLa cells were divided into five groups; (1) untreated without any transfection, (2) mock with Z2827-M67/3'UTR transfection and X-tremeGENE reagent, (3) negative control with Z2827-M67/3'UTR transfection alone, (4) test with miR-30a mimic and Z2827-M67/3'UTR transfection and (5) scramble with miR-30a scramble and Z2827-M67/3'UTR transfection. The MTT assay was performed to evaluate cell survival and cytotoxicity in each group. Real-time RT-PCR was applied for the ITGA4 expression analysis. The findings of this study showed that miR-30a downregulated ITGA4 expression and had no effect on the cell survival. Due to the silencing effect of miR-30a on the ITGA4 gene expression, this agent could be considered as a potential tool for cancer and immune disorders therapy.

Background and Objectives: Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. CABP2 mutations have been reported to cause moderate HL. Here, we report the whole exome sequencing (WES) of a proband presenting with prelingual, severe HL in an Iranian family. Methods: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 2 affected members. After excluding mutations in the GJB2 gene and 7 other most common autosomal recessive nonsyndromic HL (ARNSHL) genes via Sanger sequencing and genetic linkage analysis in the family, WES was utilized to find the possible etiology of the disease. Results: WES results showed a novel rare variant (c.311G>A) in the CABP2gene.This missense variant in the exon 4 of the CABP2gene meets the criteria of being pathogenic according to the American College of Medical Genetics and Genomics (ACMG) interpretation guidelines. Conclusions: Up to now, 3 mutations have been reported for the CABP2gene to cause moderate ARNSHL in different populations. Our results show that CABP2variantsalso cause severe ARNSHL, adding CABP2to the growing list of genes that exhibit phenotypic heterogeneity. Expanding our understanding of the mutational spectrum of HL genes is an important step in providing the correct clinical molecular interpretation and diagnosis for patients.

To determine the prevalence and types of SLC26A4 mutations and the relevant phenotypes in a series of Iranian deaf patients.A descriptive laboratory study.One hundred and twenty-one families including 60 unrelated patients and 61 unrelated multiplex families with autosomal recessive deafness were included. In the 61 multiplex families, linkage was conducted for short tandem repeats (STRs) of the DFNB4. Selected individuals from the linked families and all of the 60 deaf individuals were subjected to sequencing of SLC26A4.Seven out of the 61 (11.5%) families were linked to the locus which upon further inquiry led to identification of eight different mutations. Also, five out of the 60 (8.3%) patients were positive for the mutations. The SLC26A4 mutations clarified in 9.1% (12 families) of total investigated alleles included: c.2106delG, c.65-66insT, c.881-882delAC, c.863-864insT, c.1226G> A, c.1238A> G, c.1334T> G, c.1790T> C, c.1489G> A, c.919-2A> G (IVS7-2A> G), c.1412delT, and c.1197delT. Six out of 12 (50%) families with mutations were confirmed to be Pendred syndrome (PS).The results probably suggest a high prevalence and specificity of SLC26A4 mutations among Iranian deaf patients. Molecular study of SLC26A4 may lead to elucidation of the population-specific mutation profile which is of importance in diagnostics of deafness.