Evaluation of the expression profile of mRNAs and lncRNAs in cumulus cells associated with polycystic ovary syndrome and pregnancy.

Objectives: Polycystic ovary syndrome (PCOS), the primary cause of anovulatory infertility in women, may change the gene expression profile of cumulus cells. In human ART (assisted reproductive technology), gene expression profiling in cumulus cells, a non-invasive method, may be used to identify the most competent oocytes. We aim to identify key genes according to the network-based data and assess the suitability of these genes as markers to predict oocyte competence and PCOS diagnosis. Materials and Methods: The GSE34526 microarray dataset was obtained from the Gene Expression Omnibus (GEO) database. The function and pathway enrichment analysis for DEGs were analyzed. A protein-protein interaction (PPI) network analysis and candidate gene screening were conducted. A two-layer network consisting of mRNA and lncRNA was constructed. Expression levels of hub genes were verified using quantitative RT-PCR (qRT-PCR). Results: A total of 2721 DEGs were retained. The PPI network of selected genes associated with the biological process of "cell communication" was analyzed, and the first 10 key genes were determined by degree. Additionally, 2 hub genes and 2 hub lncRNAs, including STAT3, RHOA, GAS5, and LINC01116, were selected from the lncRNA-mRNA network. Finally, expression levels of STAT3, RHOA, GAS5, and LINC01116 were significantly increased in the cumulus cells of PCOS patients compared to the control group (P<0.05). However, there was no significant difference in expression between the pregnant and non-pregnant groups. Conclusion: STAT3, RHOA, GAS5, and LINC01116 may serve as possible diagnostic markers for PCOS. However, further studies on a larger population are needed to validate this finding.

A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation.

INTRODUCTION: Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients' manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established. METHODS: Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2. RESULTS: Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation. CONCLUSION: By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. Also, reviewing the literature shows that, contrary to previous claims, different genotypes occur in the CDH23 gene allelic disorders, and there is no clear-cut genotype-phenotype correlation.

Dysregulation of RNA interference components in COVID-19 patients.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals. RESULTS: Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.

The expression of miRNA-152-3p and miRNA-185 in tumor tissues versus margin tissues of patients with chemo-treated breast cancer.

OBJECTIVE: Breast cancer (BC) is the most significant and lethal type of cancer in women. Although there are many newly develop chemotherapy drugs for patients with BC treating at various stages, drug resistance is the most important obstacle in their effectiveness for BC treatment. On the other hand, microRNAs are considered key regulators of genes involved in carcinogenesis and chemoresistance in cancers. The purpose of this study was to evaluate the role of miR-152-3p and miR-185 in intrinsic chemoresistance and proliferation of BC. In addition, the potential role of these miRNAs during chemoresistance was evaluated through possible signaling pathways. RESULTS: Here, miR-152-3p was significantly downregulated in tumor tissues compared to the corresponding margin tissues in patients with BC (p-value ≥ 0.04407 and fold change = - 2.0552). In contrast, no statistically significant difference was observed in the miR-185 expression between the two groups. Furthermore, no significant correlation was found between the expression of these two miRNAs and subfactors, including cancer family history, abortion, and age. Downregulation of miR-152-3p could be considered a promising regulator of BC chemoresistance.

An interdependence between GAPVD1 gene polymorphism, expression level and response to interferon beta in patients with multiple sclerosis.

Interferon-ß (IFN-ß) is among the first drugs used for reducing the symptoms of multiple sclerosis (MS). Many studies show that the genetic predisposition of patients might modulate their response to IFN-ß treatment. In this study GAPVD1 gene expression and the genotyping of rs2291858 variant were analysed in 100 responder and 100 non-responder patients with MS treated using IFN-ß. Moreover, rs2291858 genotyping was performed for 200 patients with MS and 200 healthy controls. GAPVD1 expression was significantly increased in the responder patients than in non-responders and the distribution of rs2291858 polymorphism was significantly different between them. The GAPVD1 expression level in AA genotype of the responder group was higher than that in other genotypes of these two groups. The results show that the GAPVD1 expression level and rs2291858 genotype probably affect the response to IFN- ß in patients with MS.

Connection of miR-185 and miR-320a expression levels with response to interferon-beta in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by neurodegeneration in the CNS. Interferon-beta (IFN-ß) is an FDA-approved drug used as the first-line treatment for relapse-remitting multiple sclerosis (RRMS). The exact mechanism of IFN-ß during the treatment of RRMS still remains unknown. Recently, many studies have shifted towards the role of miRNAs in the treatment of MS patients. METHODS: Herein, the expression level of miR-185-5p and miR-320a has been evaluated in order to candidate them as novel biomarkers for monitoring the response to IFN-ß therapy. For this purpose, one-hundred whole blood samples from patients with RRMS were collected, consisting of 50 responders and 50 non-responders to IFN-ß therapy. To predict the possible molecular mechanisms of IFN-ß and highlight the role of these miRNAs, in silico analysis was applied to enrich the signaling pathways which may be involved based on the target genes of miR-185-5p and miR-320a. RESULTS: It is identified that the differentially expressed miR-185-5p was statistically significant between the two treated groups with IFN-ß. Furthermore, MAPK signaling pathway was suggested as the main non-canonical pathway involved in IFN-ß therapy. CONCLUSION: miR-185-5p could be considered as a novel biomarker for monitoring the response to IFN-ß therapy.

miR-504 expression level is increased in multiple sclerosis patients responder to interferon-beta.

Multiple sclerosis is immune-mediated disease of the central nervous system characterized by demyelination in axons. IFN-ß is first-line treatment of MS. Biomarkers are needed for early prediction of responders and non-responders to therapy in the first month of treatment to avoid further disabilities. In this study, we analyzed the expression level of miR-504 and miR-711 in 52 IFN-ß responder patients in comparison to 53 non-responders. In the next step, the in-silico analysis was used to enrich related signaling pathways. The expression level of miR-504 was significantly higher in patients who respond to IFN-ß therapy, compared with non-responders and we obtain related statistically significant KEGG molecular signaling pathways. Our findings suggest that miR-504 can be considered as a novel biomarker for response to IFN-b therapy.