Deregulation of miR-1245b-5p and miR-92a-3p and their potential target gene, GATA3, in epithelial-mesenchymal transition pathway in breast cancer.

BACKGROUND: MicroRNAs (miRNAs) are small molecules that have prominent roles in tumor development and metastasis and can be used for diagnostic and therapeutic purposes. This study evaluated the expression of miR-92a-3p and miR-1245b-5p and their potential target gene, GATA3 in patients with breast cancer (BC). MATERIALS AND METHODS: In the search for BC-related microRNAs, miR-124b-5p and miR-92a-3p were selected using Medline through PubMed, miR2disease, miRcancer and miRTarBase. Moreover, target gene GATA3 and their possible interaction in the regulating epithelial-mesenchymal transition (EMT) and invasion was evaluated using in silico tools including miRTarBase, TargetScan, STRING-db, and Cytoscape. The expression level of miR-92a-3p, miR1245b-5p, and GATA3 were assessed on extracted RNAs of tumor and nontumor tissues from 36 patients with BC using qPCR. Additionally, clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node were taken into consideration and the diagnostic power of these miRNAs and GATA3 was evaluated using the ROC curve analysis. RESULTS: In silico evaluation of miR-92a-3p and miR-1245b-5p supports their potential association with EMT and invasion signaling pathways in BC pathogenesis. Comparing tumor tissues to nontumor tissues, we found a significant downregulation of miR-1245b-5p and miR-92a-3p and upregulation of GATA3. Patients with BC who had decreased miR-92a-3p expression also had higher rates of advanced stage/grade and ER expression, whereas decreased miR-1245b-5p expression was only linked to ER expression and was not associated with lymph node metastasis. The AUC of miR-1245b-5p, miR-92a-3p, and GATA3 using ROC curve was determined 0.6449 (p = .0239), 0.5980 (p = .1526), and 0.7415 (p < .0001), respectively, which showed a significant diagnostic accuracy of miR-1245b-5p and GATA3 between the BC patients and healthy individuals. CONCLUSION: MiR-1245b-5p, miR-92a-3p, and GATA3 gene contribute to BC pathogenesis and they may be having potential regulatory roles in signaling pathways involved in invasion and EMT pathways in BC pathogenesis, as a result of these findings. More research is needed to determine the regulatory mechanisms that they control.

Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells.

Multiple sclerosis (MS) is a chronic autoimmune disease that degenerates the central nervous system (CNS). B cells exacerbate the progression of CNS lesions in MS by producing auto-antibodies, pro-inflammatory cytokines, and presenting auto-antigens to activated T cells. Long non-coding RNAs (lncRNAs) play a crucial role in complex biological processes and their stability in body fluids combined with their tissue specificity make these biomolecules promising biomarker candidates for MS diagnosis. In the current study, we investigated memory B cell-specific lncRNAs located, on average, less than 50 kb from differentially expressed protein-coding genes in MS patients compared to healthy individuals. Moreover, we included in our selection criteria lncRNA transcripts predicted to interact with microRNAs with established involvement in MS. To assess the expression levels of lncRNAs and their adjacent protein-coding genes, quantitative reverse transcription PCR was performed on peripheral blood mononuclear cells samples of 50 MS patients compared to 25 controls. Our results showed that in relapsing MS patients, compared to remitting MS patients and healthy controls, lncRNA RP11-530C5.1 was up-regulated while AL928742.12 was down-regulated. Pearson's correlation tests showed positive correlations between the expression levels of RP11-530C5.1 and AL928742.12 with PAWR and IGHA2, respectively. The results of the ROC curve test demonstrated the potential biomarker roles of AL928742.12 and RP11-530C5.1. We conclude that these lncRNAs are potential markers for detection of relapsing MS patients.

LncRNAs associated with multiple sclerosis expressed in the Th1 cell lineage.

Multiple sclerosis (MS) is a type of inflammatory and demyelinating disorder of the central nervous system in which immune-mediated inflammatory processes are elicited by secreted cytokines from T helper (Th)-1 and Th17 cells. While some protein-coding genes expressed in T cell types have established involvement in MS disease progression, little is understood about the roles of long noncoding RNAs (lncRNAs) within the disease landscape. LncRNAs, noncoding RNAs longer than 200 nucleotides, likely control gene expression and function of Th1 cells, and offer the potential to act as therapeutic and biomarker candidates for MS. We identified lncRNAs in Th1 cells linked to MS. Expression levels of candidate lncRNAs and genes were evaluated in 50 MS patients and 25 healthy controls using quantitative real-time polymerase chain reaction, and their correlations were assessed. LncRNAs encoded by AC007278.2 and IFNG-AS1-001 showed significantly higher expression in relapsing Phase MS patients whereas IFNG-AS1-003 was elevated in patients in the remitting phase compared with relapsing patients. Collectively, these misregulated lncRNAs may provide valuable tools to understand the relationships between lncRNAs and MS, and possibly other related disorders.

Integrative Analysis of lncRNAs in Th17 Cell Lineage to Discover New Potential Biomarkers and Therapeutic Targets in Autoimmune Diseases.

Th17 cells play a critical role in the pathogenesis of autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, and inflammatory bowel disease. Despite the extensive investigation into this T cell lineage, little is understood regarding the role of Th17 lineage-specific lncRNAs (long non-coding RNAs) > 200 nt. lncRNAs may influence disease through a variety of mechanisms; their expression could be regulated by SNPs. lncRNAs can also affect the expression of neighboring genes or complementary miRNAs, and their expression may have lineage-specific patterns. In the system biology study presented here, the effective lncRNAs from different criteria were predicted for each autoimmune disease, and we then evaluated their expression levels in 50 MS patients compared to 25 controls using qRT-PCR. We identified changes in the expression levels of AL450992.2, AC009948.5, and RP11-98D18.3 as potential peripheral blood mononuclear cell (PBMC) biomarkers for MS among our studied lncRNAs in which co-expression analysis of AL450992.2 had the most AUCs, and the relationship to RORC was also assessed. We propose that the recurrently deregulated lncRNAs identified in this report could provide a valuable resource for studies aimed at delineating the relationship between functional lncRNAs and autoimmune disorders.

Upregulation of CD4+T-Cell Derived MiR-223 in The Relapsing Phase of Multiple Sclerosis Patients.

OBJECTIVE: MicroRNAs (miRNA) are a class of non-coding RNAs which play key roles in post-transcriptional gene regulation. Previous studies indicate that miRNAs are dysregulated in patients with multiple sclerosis (MS). Th17 and regulatory T (Treg) cells are two subsets of CD4+T-cells which have critical functions in the onset and progression of MS. The current study seeks to distinguish fluctuations in expression of CD4+T-cell derived miR-223 during the relapsing-remitting (RR) phase of MS (RR-MS), as well as the expressions of Th17 and Treg cell markers. MATERIALS AND METHODS: This experimental study used real-time quantitative polymerase chain reaction (qRT-PCR) to evaluate CD4+ T cell derived miR-223 expression patterns in patients that experienced either of the RR-MS phases (n=40) compared to healthy controls (n=12), along with RNA markers for Th17 and Treg cells. We conducted flow cytometry analyses of forkhead box P3 (FOXP3) and RAR-related orphan receptor γt (RORγt) in CD4+T-cells. Putative and validated targets of miR-223 were investigated in the miRWalk and miRTarBase databases, respectively. RESULTS: miR-223 significantly upregulated in CD4+T-cells during the relapsing phase of RR-MS compared to the remitting phase (P=0.000) and healthy individuals (P=0.036). Expression of RORγt, a master transcription factor of Th17, upregulated in the relapsing phase, whereas FOXP3 upregulated in the remitting phase. Additionally, potential targets of miR-223, STAT1, FORKHEAD BOX O (FOXO1) and FOXO3 were predicted by in silico studies. CONCLUSION: miR-223 may have a potential role in MS progression. Therefore, suppression of miR-223 can be proposed as an appropriate approach to control progression of the relapsing phase of MS.