Overview of host miRNA properties and their association with epigenetics, long non-coding RNAs, and Xeno-infectious factors

MicroRNA-derived structures play impressive roles in various biological processes. So dysregulation of miRNAs can lead to different human diseases. Recent studies have extended our comprehension of the control of miRNA function and features. Here, we overview some remarkable miRNA properties that have potential implications for the miRNA functions, including different variants of a miRNA called isomiRs, miRNA arm selection/arm switching, and the effect of these factors on miRNA target selection. Besides, we review some aspects of miRNA interactions such as the interaction between epigenetics and miRNA (different miRNAs and their related processing enzymes are epigenetically regulated by multiple DNA methylation enzymes. moreover, DNA methylation could be controlled by diverse mechanisms related to miRNAs), direct and indirect crosstalk between miRNA and lnc (Long Non-Coding) RNAs as a further approach to conduct intercellular regulation called �competing endogenous RNA� (ceRNA) that is involved in the pathogenesis of different diseases, and the interaction of miRNA activities and some Xeno-infectious (virus/bacteria/parasite) factors, which result in modulation of the pathogenesis of infections. This review provides some related studies to a better understanding of miRNA involvement mechanisms and overcoming the complexity of related diseases that may be applicable and useful to prognostic, diagnostic, therapeutic purposes and personalized medicine in the future. © 2021, The Author(s)

Histonedeacetylase 1 mRNA has elevated expression in clinical specimen of bladder cancer

OBJECTIVE: HDACs are among transcriptional regulatory elements that regulate key features of proliferation and differentiation in all cell types including cancerous. They may also interfere in such stages of cancer development as migration, invasion, multi-drug resistance and angiogenesis. Proven information about HDAC1 role in development of bladder cancer is limited only to cell lines in vitro. The lack of a comprehensive clinical in vivo study led us to evaluate HDAC1 expression in human clinical specimens. METHODS: We analyzed a large group of bladder cancer patients. The presence of hHDAC1 mRNAs were tracked using specific HDAC1 primers in cancer samples and the quantity of HDAC1 transcripts were quantified using real time qPCR method and was compared to those of normal bladder samples from healthy patients. RESULTS: HDAC1 mRNA expression was significantly elevated in Bladder cancer specimens. To our knowledge, this result is the first, showing an elevation in vivo in HDAC1 mRNA levels in clinically cancerous tissue of patients with bladder cancer. CONCLUSIONS: We conclude that hHDAC1 overexpression might be implicated in bladder cancer tumorigenesis and that the over-expressed HDAC1 mRNA might be a potential diagnostic marker and, a target for treatment of bladder cancer using HDACi-drugs in future

Histonedeacetylase 1 mRNA has elevated expression in clinical specimen of bladder cancer

OBJECTIVE: HDACs are among transcriptional regulatory elements that regulate key features of proliferation and differentiation in all cell types including cancerous. They may also interfere in such stages of cancer development as migration, invasion, multi-drug resistance and angiogenesis. Proven information about HDAC1 role in development of bladder cancer is limited only to cell lines in vitro. The lack of a comprehensive clinical in vivo study led us to evaluate HDAC1 expression in human clinical specimens. METHODS: We analyzed a large group of bladder cancer patients. The presence of hHDAC1 mRNAs were tracked using specific HDAC1 primers in cancer samples and the quantity of HDAC1 transcripts were quantified using real time qPCR method and was compared to those of normal bladder samples from healthy patients. RESULTS: HDAC1 mRNA expression was significantly elevated in Bladder cancer specimens. To our knowledge, this result is the first, showing an elevation in vivo in HDAC1 mRNA levels in clinically cancerous tissue of patients with bladder cancer. CONCLUSIONS: We conclude that hHDAC1 overexpression might be implicated in bladder cancer tumorigenesis and that the over-expressed HDAC1 mRNA might be a potential diagnostic marker and, a target for treatment of bladder cancer using HDACi-drugs in future

Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: A focus on white fat browning properties and thermogenic capacity

Background: Obesity has reached an alarming rate worldwide. Promoting thermogenesis via increasing the function of brown adipose tissue (BAT) or white adipose tissue (WAT) browning has been proposed as a new protective approach against obesity. The goal of this study was to evaluate the effects of Royal Jelly (RJ) and tocotrienol rich fraction (TRF) on BAT activation and WAT browning during calorie restriction diet (CRD) in obesity model. Methods: In this experimental study, 50 obese Wistar rats were randomly divided into 5 groups and then received one of the following treatments for a period of 8-week: High-fat diet (HFD), CRD, RJ + CRD, TRF + CRD, and RJ + TRF + CRD. Effects of RJ and TRF, individually and in combination on body weight and the expression of key thermoregulatory genes in WAT and BAT were examined by quantitative real-time (qRT-PCR). Also, morphological alterations were assessed by hematoxylin and eosin staining. Results: RJ (- 67.21 g ±4.84 g) and RJ + TRF (- 73.29 g ±4.51 g) significantly reduced weight gain relative to the CRD group (- 40.70 g ±6.50 g, P < 0.001). In comparison with the CRD group, RJ and RJ + TRF remarkably enhanced the uncoupling protein1 (UCP1) expression in WAT (5.81, 4.72 fold, P < 0.001) and BAT (4.99, 4.75 fold, P < 0.001). The expression of PR domain containing 16(PRDM 16), cAMP response element-binding protein1 (CREB1), P38 mitogen-activated protein kinases (P38MAPK), and Bone morphogenetic protein8B (BMP8B) have significantly increased following RJ and RJ + TRF treatments (P < 0.001). However, the expression levels of CCAAT/enhancer-binding protein beta (CEBPβ) and Bone morphogenetic protein7 (BMP7) did not remarkably change. Multilocular beige cells in WAT and compacted dense adipocytes were also observed in BAT of RJ and RJ + TRF received groups. TRF showed no substantial effects on the expression of the mentioned thermoregulatory genes and brown fat-like phenotype. Conclusion: Our results suggest that, Royal Jelly promotes thermogenesis and browning of WAT, contributing to an increase in energy expenditure. Thus, Royal Jelly may give rise to a novel dietary choice to attenuate obesity. © 2020 The Author(s)

Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

<p>Abstract</p> <p>Background</p> <p>Squamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (<it>APC</it>) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of <it>APC </it>promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and <it>APC </it>promoter methylation.</p> <p>Methods</p> <p>For evaluating the status of <it>APC </it>promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated <it>APC </it>promoter was compared with that of unmethylated patients.</p> <p>Results</p> <p>Assessment of <it>APC </it>promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of <it>APC</it>. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of <it>APC</it>. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of survival for patients with methylated <it>APC </it>promoter following their treatment. Further investigation into the association between promoter hypermethylation and tumor differentiation status indicated that patients with well differentiated tumors were more likely to develop promoter hypermethylation.</p> <p>Conclusion</p> <p>Observing similar level of <it>APC </it>promoter hypermethylation in patients with SCCE in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of SCCE. In addition, the higher rate of two-year survival for patients with unmethylated <it>APC </it>promoter as well as its relationship with tumor differentiation would suggest that this tumor suppressor could be an appropriate candidate molecular marker for evaluating tumor malignancy and predicting survival of patients subsequent to treatment.</p

MiR-330-3p and miR-485-5p as biomarkers for glioblastoma: An integrated bioinformatics and experimental study

Glioblastoma Multiforme (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and a median survival of 12�15 months. This study tried to identify the most significant miRNA biomarkers in both tissue and serum samples of GBM. GSE25632 was employed from gene expression omnibus and using WGCNA package, association of miRNA networks and clinical data was explored and brown and green modules identified as the most relevant modules. Independently, Limma package was utilized to identify differentially expressed miRNAs (DEMs) in GSE25632 by cutoff logFC > 2 and P.value < 0.05. By merging the results of Limma and WGCNA, the miRNAs that were in brown and green modules and had mentioned cutoff were selected as hub miRNAs. Performing enrichment analysis, Pathways in cancer, Prostate cancer, Glioma, p53 signaling pathway, and Focal adhesion were identified as the most important signaling pathways. Based on miRNA- target genes, has-mir-330�3p and has-mir-485�5p were identified as core miRNAs. The expression level of core miRNAs was validated by GSE90604, GSE42657, and GSE93850. We evaluated the expression level of common target genes of two detected core genes based on GSE77043, GSE42656, GSE22891, GSE15824, and GSE122498. The ability of detected miRNAs to discriminate GBM from healthy controls was assessed by area under the curve (AUC) using the ROC curve analysis. Based on TCGA database, we tested the prognostic significance of miRNAs using overall survival analysis. We evaluated the expression level of the miRNAs in tissue of 83 GBM patients and also non-tumoral adjacent (as control) tissues. We used serum samples of 34 GBM patients to evaluate the expression levels of the hub miRNAs compare to the controls. Our results showed that has-mir-330�3p and has-mir-485�5p could be potential biomarkers in GBM. © 2021 Elsevier Lt

microRNAs involved in T-cell development, selection, activation, and hemostasis

MicroRNAs (miRNAs) characterized by small, noncoding RNAs have a fundamental role in the regulation of gene expression at the post-transcriptional level. Additionally, miRNAs have recently been identified as potential regulators of various genes involved in the pathogenesis of the autoimmune and inflammatory disease. So far, the interaction between miRNAs and T lymphocytes in the immune response as a new and significant topic has not been emphasized substantially. The role of miRNAs in different biological processes including apoptosis, immune checkpoints and the activation of immune cells is still unclear. Aberrant miRNA expression profile affects various aspects of T-cell function. Accordingly, in this literature review, we summarized the role of significant miRNAs in T-cell development processes. Consequently, we demonstrated precise mechanisms that candidate miRNAs interfere in Immune response mediated by different types of T cells. We believe that a good understanding of the interaction between miRNAs and immune response contributes to the new therapeutic strategies in relation to disease with an immunological origin. © 2020 Wiley Periodicals, Inc