Background Filaggrin is a key structural epidermal protein in terminal differentiation and formation of skin barrier. The important role of filaggrin and its effects in various cutaneous and noncutaneous disorders initiated a cascade of considerable research in recent years. Loss‐of‐function mutations in FLG, the human gene encoding profilaggrin/filaggrin, is the cause of the common skin condition ichthyosis vulgaris (IV) and major genetic predisposing factor for atopic dermatitis (AD). Several null mutations in the FLG gene that lead to a decrease or absence of filaggrin in skin and predispose these conditions have been described. Objective The aim of this study was to investigative genetic polymorphism of FLG in Iranian patients with IV and AD. Methods In the current study, we carried out full sequencing of the entire FLG coding region in 30 IV patients and 30 AD patients, and also 60 healthy controls. Results In our research, we identified 43 variants reported previously and two novel variants. Conclusion In our study, in the AD and IV patients, loss‐of‐function FLG mutation was not found. This means that another mechanism other than FLG nonsense mutation is involved in the pathogenesis of these patients.

Duchenne muscular dystrophy is an X-linked recessive hereditary monogenic disorder caused by inability to produce dystrophin protein. In most patients, the expression of dystrophin lost due to disrupting mutations in open reading frame. Despite the efforts in a large number of different therapeutic approaches to date, the treatments available for DMD remain mitigative and supportive to improve the symptoms of the disease, rather than to be curative. The advent of CRISPR/Cas9 technology has revolutionized genome editing scope and considered as pioneer in effective genomic engineering. Deletions or excisions of intragenic DNA by CRISPR as well as a similar strategy with exon skipping at the DNA level induced by antisense oligonucleotides, are new and promising approaches in correcting DMD gene, which restore the expression of a truncated but functional dystrophin protein. Also, CRISPR/Cas9 technology can be used to treat DMD by removing duplicated exons, precise correction of causative mutation by HDR-based pathway and inducing the expression of compensatory proteins such as utrophin. In this study, we briefly explained the molecular genetics of DMD and a historical overview of DMD gene therapy. We in particular focused on CRISPR/Cas9-mediated therapeutic approaches that used to treat DMD.

Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an in silico approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of APTR, AC144450.1, linc00663, ZNF337.AS1, and RAMP2.AS1 lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of GATA3 was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E−04). Moreover, expression levels of APTR, AC144450.1, and ZNF337.AS1 were elevated in breast cancer tissues compared with control tissues (RME = 2.27, P value = 5.40E−03; Ratio of mean expressions = 615.95, P value = 7.39E−19 and RME = 1.78, P value = 3.40E−02, respectively). On the other hand, the expression of RAMP2.AS1 was lower in breast cancer tissues than controls (RME = 0.31, P value = 1.87E−03). Expression levels of FOXA1, ESR1, and FOXM1 and linc00663 were not significantly different between the two sets of samples. Expression of GATA3 was significantly associated with stage (P value = 4.77E−02). Moreover, expressions of FOXA1 and RAMP2.AS1 were associated with the mitotic rate (P values = 2.18E−02 and 1.77E−02, respectively). Finally, expressions of FOXM1 and ZNF337.AS1 were associated with breastfeeding duration (P values = 3.88E−02 and 4.33E−02, respectively). Based on the area under receiver operating characteristics curves, AC144450.1 had the optimal diagnostic power in differentiating between cancerous and non-cancerous tissues (AUC = 0.95, Sensitivity = 0.90, Specificity = 0.96). The combination of expression levels of all genes slightly increased the diagnostic power (AUC = 0.96). While there were several significant pairwise correlations between expression levels of genes in non-tumoral tissues, the most robust correlation was identified between linc00663 and RAMP2.AS1 (r = 0.61, P value = 3.08E−8). In the breast cancer tissues, the strongest correlations were reported between FOXM1/ZNF337.AS1 and FOXM1/RAMP2.AS1 pairs (r = 0.51, P value = 4.79E−5 and r = 0.51, P value = 6.39E−5, respectively). The current investigation suggests future assessment of the functional role of APTR, AC144450.1 and ZNF337.AS1 in the development of breast neoplasms.

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Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occursto endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs, long noncoding RNAs, and circular RNAs can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network.ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new eld of research and therapeutic options for BC patients.Methods. In this study, BC-speci c RNA expression pro les including mRNAs, miRNAs, lncRNAs, and circRNAs were retrievedfrom Gene Expression Omnibus microarray datasets, and differentially expressed(DE) items were obtained.Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted.The prognostic value of hub mRNAs in patients of BC were performed. Subsequently, a ceRNA network was established.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genesincluding FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined

Recently it has been identified that circRNAs can act as miRNAs sponge to regulate gene expression in various types of cancers to associate with cancer initiation and progression. The present study aims to identify colorectal cancer-related circRNAs and the underpinning mechanisms of circRNA/miRNA/mRNA networks in the development and progress of Colorectal Cancer. Differentially expressed circRNAs, miRNAs, and mRNAs were identified in GEO microarray datasets using the Limma package of R. Differentially expressed circRNAs analysis resulted in 23 upregulated and 31 downregulated circRNAs. CeRNAs networks were constructed by intersecting the results of predicted and experimentally validated databases, circbank and miRWalk, and DEMs and DEGs analysis using Cytoscape. Then, the functional enrichment analysis was performed for DEGs included in ceRNA networks. Followed by survival analysis, expression profile validation using TCGA and GEO data, and ROC curve analysis we reached a ceRNA sub-networks which revealed the potential regulatory effect of hsa_circ_0001955 and hsa_circ_0071681 on the survival-related genes, KLF4, MYC, CCNA2, RACGAP1, and CD44. Overall, we constructed a convoluted regulatory network and the likely mechanisms of its action in CRC, which may contribute to developing more effective approaches for early diagnosis, prognosis, and treatment of CRC.

Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occurs to endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network. ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new field of research and therapeutic options for BC patients. Methods. In this study, BC-specific RNA expression profiles including mRNAs, miRNAs, lncRNAs, and circRNAs were retrieved from Gene Expression Omnibus (GEO) microarray datasets, and differentially expressed (DE) items were obtained. Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted. The prognostic value of hub mRNAs in patients of BC were performed using GEPIA. Subsequently, a ceRNA network was established by Cytoscape.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genes including FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined possible ncRNAs (circ0007535, circ0002727, circ0005240, circ0014130, circ0044927, circ0007001, circ0089153, NORAD, MALAT1, TUG1, ZFAS1, OPI5-AS1, miR183, miR182, miR101, miR200c, miR200b, miR149, miR342, and miR1207) which could crosstalk with each other to regulate FOXO3 and RHOA through different regulatory patterns. Conclusion. These data might improve our perception of the breast tumorigenesis and could develop new field of research and therapeutic options for BC patients.