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Evaluation of miR-181b and miR-126-5p expression levels in T2DM patients compared to healthy individuals: Relationship with NF-κB gene expression.
Dehghani, M, Aghaei Zarch, SM, Vahidi Mehrjardi, MY, Nazari, M, Babakhanzadeh, E, Ghadimi, H, Zeinali, F, Talebi, M
Endocrinologia, diabetes y nutricion. 2020;(7):454-460
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder whose prevalence is rising very fast across the world. Diagnosis of this disease in early stages (pre-diabetic stage) plays an important role in reducing mortality associated with this disorder. miRNAs, as key players in the pathogenesis of T2DM, have been investigated in several studies. Furthermore, their expression profile changes in the early stages of diabetes mellitus in body fluids such as serum, peripheral blood, and peripheral blood mononuclear cell (PBMC) have been studied. Due to their high stability and the presence of non-invasive sensitive methods for their measurement, such as real-time PCR, they can be used for early diagnosis of T2DM as a biomarker. In this experimental study, the expression levels of miR-181b, miR-126-5p, and NF-κB were measured in patients with T2DM, pre-diabetic subjects, and healthy controls in a Yazd population. MATERIAL AND METHOD Ninety asymptomatic subjects including 30 T2DM, 30 pre-diabetic, and 30 healthy subjects (diagnosis based on WHO criteria) were included in this study. Real-time PCR was used to measure the expression levels of miR-181b and miR-126-5p. Moreover, the NF-κB expression level was also measured to determine its relationship with these two microRNAs. RESULT In this study, the expression level of miR-181b and miR-126-p decreased gradually in pre-diabetic as well as T2DM subjects compared to healthy controls. Furthermore, our study showed a significant negative correlation between these two miRNAs and NF-κB for the first time. CONCLUSION These results introduce these anti-inflammatory miRNAs as powerful tools for early diagnosis of T2DM.
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Expression of Salivary miRNA 21 in Oral Submucous Fibrosis (OSMF): An Observational Study.
Prasad, SR, Pai, A, Shyamala, K, Yaji, A
MicroRNA (Shariqah, United Arab Emirates). 2020;(4):295-302
Abstract
OBJECTIVE To observe the expression patterns of salivary mRNA 21 in different stages and grades of OSMF and also in habitual areca nut chewers without OSMF. SUBJECTS AND METHODS The study consisted of a total of 185 samples, where 61 patients had chewing habits (chewing gutkha and other forms of areca nut) and had OSMF (Group 1). 61 patients had chewing habits but did not have OSMF (Group 2), and 63 were normal healthy patients (control group) without any chewing habits (Group 3). Unstimulated saliva samples were collected from patients following the standard operating procedures. miRNA 21 was isolated and purified from saliva samples using the miRNeasy Mini Kit, Qiagen. The primers for miRNA relative quantification analysis were designed using the Primer Express software of Applied Biosystems. Quantification of all the samples was carried out using SYBR chemistry in an Applied Biosystems Real-Time PCR. RESULTS There was no statistically significant difference between the demographic characteristics of patients. There was a statistically significant difference between the expressions of miRNA 21 amongst the three groups noted in Kruskal Wallis test. (<0.001*) A post hoc test was perfomed to confirm the statistical difference between patients within all three groups. There was no statistically significant difference noted between the OSMF group and patients with chewing habits group (G1 vs. G2 p: 0.10), but there was a significant difference when compared with normal patients. (G1 vs. G3 p: <0.001*) and (G2 vs. G3 <0.001*). CONCLUSION This study concludes that miRNA 21 is overexpressed in OSMF and chewing habit patients. But the expression levels were not significantly associated with the severity of the disease process. A long term and large scale studies are required to assess its application as a diagnostic profibrotic marker in OSMF.
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Exosomal microRNAs: novel players in cervical cancer.
Nahand, JS, Vandchali, NR, Darabi, H, Doroudian, M, Banafshe, HR, Moghoofei, M, Babaei, F, Salmaninejad, A, Mirzaei, H
Epigenomics. 2020;(18):1651-1660
Abstract
Cervical cancer ranks fourth for both mortality and morbidity in women globally. Exosomes are considered as extracellular vesicles, secreted continuously by many cells with a size range from 30 to 150 nm. Exosomes can encapsulate microRNAs (miRNAs) and release them for cellular communications. This exosome-induced miRNA transfer is a novel strategy for genetic exchange among cells. This trafficking modality affects many pathological as well as physiological conditions. Moreover, exosomes can protect the miRNAs against harsh environments and keep them very stable. Given that a variety of exosomal miRNAs derived from cervical cancer cells can be targeted to recipient cells and contribute to tumorgenesis, it has been documented that exosomal miRNAs could be applied as diagnostic and therapeutic biomarkers in the treatment of cervical cancer. Herein, we summarize the pathologic and diagnostic roles of exosomal miRNAs in the cervical cancer. Moreover, we highlight the roles of exosomal miRNAs in other cancers.
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Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression.
Varghese, E, Liskova, A, Kubatka, P, Mathews Samuel, S, Büsselberg, D
Biomolecules. 2020;(2)
Abstract
Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor suppressor genes including the genes that regulate tumor angiogenesis. Hypoxia inducible factor-1 alpha (HIF-1α) signaling is a central axis that activates oncogenic signaling and acts as a metabolic switch in endothelial cell (EC) driven tumor angiogenesis. Tumor angiogenesis driven by metabolic reprogramming of EC is crucial for tumor progression and metastasis in many different cancers, including breast cancers, and has been linked to aberrant miRNA expression profiles. In the current article, we identify different miRNAs that regulate tumor angiogenesis in the context of oncogenic signaling and metabolic reprogramming in ECs and review how selected phytochemicals could modulate miRNA levels to induce an anti-angiogenic action in breast cancer. Studies involving genistein, epigallocatechin gallate (EGCG) and resveratrol demonstrate the regulation of miRNA-21, miRNA-221/222 and miRNA-27, which are prognostic markers in triple negative breast cancers (TNBCs). Modulating the metabolic pathway is a novel strategy for controlling tumor angiogenesis and tumor growth. Cardamonin, curcumin and resveratrol exhibit their anti-angiogenic property by targeting the miRNAs that regulate EC metabolism. Here we suggest that using phytochemicals to target miRNAs, which in turn suppresses tumor angiogenesis, should have the potential to inhibit tumor growth, progression, invasion and metastasis and may be developed into an effective therapeutic strategy for the treatment of many different cancers where tumor angiogenesis plays a significant role in tumor growth and progression.
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The Effect of Methylselenocysteine and Sodium Selenite Treatment on microRNA Expression in Liver Cancer Cell Lines.
Lendvai, G, Szekerczés, T, Kontsek, E, Selvam, A, Szakos, A, Schaff, Z, Björnstedt, M, Kiss, A
Pathology oncology research : POR. 2020;(4):2669-2681
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Abstract
The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells, providing a great potential for treating cancer cells being highly resistant to cytostatic drugs. However, selenium treatment may affect microRNA (miRNA) expression as the pattern of circulating miRNAs changed in a placebo-controlled selenium supplement study. This necessitates exploring possible changes in the expression profiles of miRNAs. For this, miRNAs being critical for liver function were selected and their expression was measured in hepatocellular carcinoma (HLE and HLF) and cholangiocarcinoma cell lines (TFK-1 and HuH-28) using individual TaqMan MicroRNA Assays following selenite or MSC treatments. For establishing tolerable concentrations, IC50 values were determined by performing SRB proliferation assays. The results revealed much lower IC50 values for selenite (from 2.7 to 11.3 μM) compared to MSC (from 79.5 to 322.6 μM). The treatments resulted in cell line-dependent miRNA expression patterns, with all miRNAs found to show fold change differences; however, only a few of these changes were statistically different in treated cells compared to untreated cells below IC50. Namely, miR-199a in HLF, miR-143 in TFK-1 upon MSC treatment, miR-210 in HLF and TFK-1, miR-22, -24, -122, -143 in HLF upon selenite treatment. Fold change differences revealed that miR-122 with both selenium compounds, miR-199a with MSC and miR-22 with selenite were affected. The miRNAs showing minimal alterations included miR-125b and miR-194. In conclusion, our results revealed moderately altered miRNA expression in the cell lines (less alterations following MSC treatment), being miR-122, -199a the most affected and miR-125b, -194 the least altered miRNAs upon selenium treatment.
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Modulatory Role of Vaginal-Isolated Lactococcus lactis on the Expression of miR-21, miR-200b, and TLR-4 in CAOV-4 Cells and In Silico Revalidation.
Rahbar Saadat, Y, Pourseif, MM, Zununi Vahed, S, Barzegari, A, Omidi, Y, Barar, J
Probiotics and antimicrobial proteins. 2020;(3):1083-1096
Abstract
Ovarian cancer (OC) is a leading cause of death among women worldwide. Various evidences suggest that oncomiRs and Toll-like receptor 4 (TLR-4) signaling pathways appear to be key players in the initiation and progression of OC. It seems there exists a continuous intercommunication between cancer cells and normal microbiota of the vagina. The biological impacts of vaginal isolated lactococcus lactis on CAOV-4 cells were investigated using several molecular biology experiments, including flow cytometry, DAPI staining, DNA ladder, and scratch assay. The expression of microRNAs (miRNAs/miRs) 21, 200b, and TLR-4 in the CAOV-4 cells was also evaluated by the real-time RT-PCR assay. Furthermore, an integrative in silico analysis was conducted using normalized web-available microarray data (GSE14407) to revalidate the experimental findings and identify potential biomarkers in ovarian cancer. Protein-protein interactions (PPIs) network was studied by means of the STRING database using Cytoscape v3.6.1. The miRNA target genes were identified using the dbDEMC v2.0, miRTarBase, and miRDB databases. Our data demonstrated that L. lactis probiotic candidate downregulates TLR-4, miR-21, and miR-200b expression levels, which correlates with induction of apoptosis as confirmed by DAPI staining, DNA ladder assay, annexin V/PI staining, and inhibition of migration validated by scratch assay. By in silico analysis, several targets (miR-17-5p-BCL2, miR-21-5p-MKNK2, miR-129-5p-CDK6) were identified, while BCL2, CCNB1, and VEGFA were found as the hub proteins in the miRNA-target and PPI networks. Further, downregulation of the TLR-4, miR-21, and miR-200b was partially validated by the in silico analysis. Based on our findings, the vaginal isolated probiotic strain presents great potential to control the ovarian cancer which may provide beneficial impact on the clinical management of ovarian cancer.
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The Polymorphism of miR-146a (rs2910164) and Breast Cancer Risk: A Meta-Analysis of 17 Studies.
Moossavi, M, Shojaee, M, Musavi, M, Ibrahimi, R, Ibrahimi, M, Khorasani, M
MicroRNA (Shariqah, United Arab Emirates). 2020;(4):310-320
Abstract
BACKGROUND Single-Nucleotide Polymorphisms (SNPs) in genes responsible for coding microRNAs (miRNAs) are shown to be crucial in progression of Breast Cancer (BC). OBJECTIVE The purpose of this meta-analysis is to obtain more definitive and reliable results due to the ambiguity and inconsistency of the previous findings in this regard. This study aimed at clarifying the association of mir14a polymorphisms with breast cancer. METHODS We searched PubMed, EMBASE, Web of Science and Google Scholar databases for papers published before August 10, 2019. Afterward, genotypes' distribution, genotyping methods and ethnicity groups were extracted and Overall analyses were conducted. A total number of seventeen researches on 7676 subjects and 7476 controls were found to meet our criteria in this meta-analysis. RESULTS Our observations confirmed the increased risk in breast cancer with rs 2910164 polymorphism in three genetic models: allele contrast fixed genetic model, Recessive fixed genetic model and CC vs. GG genetic model (P value 0.0109, 0.0404 and 0.0019, respectively). CONCLUSION The rs2910164 polymorphism is associated with increased breast cancer risk. We suggest that more multicenter studies with larger samples investigate this matter to further clarify the association and verify our findings.
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MicroRNAs and exosomes: key players in HIV pathogenesis.
Sadri Nahand, J, Bokharaei-Salim, F, Karimzadeh, M, Moghoofei, M, Karampoor, S, Mirzaei, HR, Tabibzadeh, A, Jafari, A, Ghaderi, A, Asemi, Z, et al
HIV medicine. 2020;(4):246-278
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Abstract
OBJECTIVES HIV infection is well known to cause impairment of the human immune system, and until recently was a leading cause of death. It has been shown that T lymphocytes are the main targets of HIV. The virus inactivates T lymphocytes by interfering with a wide range of cellular and molecular targets, leading to suppression of the immune system. The objective of this review is to investigate to what extent microRNAs (miRNAs) are involved in HIV pathogenesis. METHODS The scientific literature (Pubmed and Google scholar) for the period 1988-2019 was searched. RESULTS Mounting evidence has revealed that miRNAs are involved in viral replication and immune response, whether by direct targeting of viral transcripts or through indirect modulation of virus-related host pathways. In addition, exosomes have been found to act as nanoscale carriers involved in HIV pathogenesis. These nanovehicles target their cargos (i.e. DNA, RNA, viral proteins and miRNAs) leading to alteration of the behaviour of recipient cells. CONCLUSIONS miRNAs and exosomes are important players in HIV pathogenesis. Additionally, there are potential diagnostic applications of miRNAs as biomarkers in HIV infection.
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MicroRNAs and microbiota: Is there a cross talk?
Rizk, M, Tüzmen, S
Drugs of today (Barcelona, Spain : 1998). 2020;(3):211-226
Abstract
MicroRNAs (miRNAs) are a form of single-stranded RNA molecules with a length that varies between 18 and 23 nucleotides and which are synthesized in the nucleus but function in the cytoplasm. miRNAs function endogenously and bind to complementary sequences in either the coding regions or the 3' untranslated regions (UTRs) of target messenger RNAs (mRNAs). This indicates that miRNAs operate in a post-transcriptional manner. miRNAs play essential roles in various biological events, and have thus been found extracellularly in different body fluids such as saliva, urine and plasma. miRNAs are distinguished in the gut mainly by examining content from intestines and feces. The gastrointestinal tract is infested with a variety of microorganisms that are initially inherited from the mother; however, those microorganisms develop as a result of changes in dietary intakes and environmental factors. The gut microbiota are therefore shaped differently in different individuals due to several contributing factors such as genetics, diet and state of disease, and have a great impact on the host during phases of disease and homeostasis.
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Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer.
Figueroa-González, G, Carrillo-Hernández, JF, Perez-Rodriguez, I, Cantú de León, D, Campos-Parra, AD, Martínez-Gutiérrez, AD, Coronel-Hernández, J, García-Castillo, V, López-Camarillo, C, Peralta-Zaragoza, O, et al
Genes. 2020;(9)
Abstract
BACKGROUND Serine Threonine Kinase 11 (STK11), also known as LKB1, is a tumor suppressor gene that regulates several biological processes such as apoptosis, energetic metabolism, proliferation, invasion, and migration. During malignant progression, different types of cancer inhibit STK11 function by mutation or epigenetic inactivation. In Head and Neck Cancer, it is unclear what mechanism is involved in decreasing STK11 levels. Thus, the present work aims to determine whether STK11 expression might be regulated through epigenetic or post-translational mechanisms. METHODS Expression levels and methylation status for STK11 were analyzed in 59 cases of head and neck cancer and 10 healthy tissue counterparts. Afterward, we sought to identify candidate miRNAs exerting post-transcriptional regulation of STK11. Then, we assessed a luciferase gene reporter assay to know if miRNAs directly target STK11 mRNA. The expression levels of the clinical significance of mir-100-3p, -5p, and STK11 in 495 HNC specimens obtained from the TCGA database were further analyzed. Finally, the Kaplan-Meier method was used to estimate the prognostic significance of the miRNAs for Overall Survival, and survival curves were compared through the log-rank test. RESULTS STK11 was under-expressed, and its promoter region was demethylated or partially methylated. miR-17-5p, miR-106a-5p, miR-100-3p, and miR-100-5p could be negative regulators of STK11. Our experimental data suggested evidence that miR-100-3p and -5p were over-expressed in analyzed tumor patient samples. Luciferase gene reporter assay experiments showed that miR-100-3p targets and down-regulates STK11 mRNA directly. With respect to overall survival, STK11 expression level was significant for predicting clinical outcomes. CONCLUSION This is, to our knowledge, the first report of miR-100-3p targeting STK11 in HNC. Together, these findings may support the importance of regulation of STK11 through post-transcriptional regulation in HNC and the possible contribution to the carcinogenesis process in this neoplasia.