Expression Of miR-27a Research Articles

MicroRNA-133 suppresses cell viability and migration of rheumatoid arthritis fibroblast-like synoviocytes by down-regulation of MET, EGFR, and FSCN1 expression.

Aberrant proliferation and migration of fibroblast-like synoviocytes (FLS) are major characteristics of rheumatoid arthritis (RA). MicroRNA-133 (miR-133) is a tumor-suppressive miRNA that targets various genes responsive for cell proliferation and migration. The aim of this study was to examine the effect of miR-133 on RA FLS. A high throughput miRNA microarray was performed in synovium from mice with collagen-induced arthritis (CIA). Expression levels of miR-133 and the putative targets were determined in synovium and FLS from patients with RA and mice with CIA. Overexpression of miR-133 in RA FLS was performed by lentiviral vector-mediated transfer of precursor miRNA (pre-miR). The expression of miR-133a/b was decreased in the joint tissue and FLS of CIA mice, as determined by miRNA array and qRT-PCR. Down-regulation of miR-133a/b expression could also be observed in synovium and FLS from patients with RA. Overexpression of miR-133 reduced cell viability and migration of RA FLS, with decreased levels of FSCN1, EGFR, and MET. Our findings demonstrated the inhibitory effects of miR-133 on FLS viability and migration, and might contribute to the pharmacologic development of miR-133 therapeutics in patients with RA.

The potential role of miR-27a and miR-320a in metabolic syndrome in obese Egyptian females

BackgroundMetabolic syndrome (MetS) is a combination of many health complications, such as obesity, high blood pressure, hyperlipidemia, hyperglycemia, and insulin resistance, with an increasing threat of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. As the MetS develops, an alteration in the expression of some genes regulated by circulating microRNAs may also develop as a consequence. TaqMan microRNA primers specific for both miR-27a and miR-320a were used to estimate their expression levels in plasma samples collected from two groups: obese females with metabolic syndrome (n = 49) and lean healthy female volunteers (n = 23), to detect if their expression levels were deregulated with MetS. ResultsThe study results revealed that miR-27a was upregulated in the plasma of MetS group compared to the healthy controls, while miR-320a was downregulated (p ≤ 0.005). There was a highly significantly positive correlation between miR-27a expression and body mass index (BMI), waist circumference (WC), fasting blood glucose (FBG), insulin resistance (represented as HOMA-IR), and triglycerides (TG), while it showed significantly negative correlation only with HDL-cholesterol (p ≤ 0.0001). miR-320a showed significantly negative correlation with BMI, WC, waist-hip ratio (WHR), FBG, HOMA-IR, and TG. The expression value of miR-320a was positively correlated with HDL-cholesterol. Area under the curves (AUC) was equal to 1.000 for both microRNAs. ConclusionOur study added more evidence that monitoring changes in expression levels of both miR-27a and miR-320a in MetS patients could help in the evaluation of disease progression, risk, and susceptibility.

Jinlida Granules Reduce Obesity in db/db Mice by Activating Beige Adipocytes.

Recent studies indicate existence of beige adipocytes in adults. Upon activation, beige adipocytes burn energy for thermogenesis and contribute to regulation of energy balance. In this study, we have analyzed whether Jinlida granules (JLD) could activate beige adipocytes. JLD suspended in 0.5% carboxymethyl cellulose (CMC) was gavage fed to db/db mice at a daily dose of 3.8 g/kg. After 10 weeks, body weight, biochemical, and histological analyses were performed. In situ hybridization, immunofluorescence, and western blotting were conducted to test beige adipocyte activation in mice. X9 cells were induced with induction medium and maintenance medium containing 400 μg/mL of JLD. After completion of induction, cells were analyzed by Nile red staining, time polymerase chain reaction (PCR), western blotting, and immunofluorescence to understand the effect of JLD on the activation of beige adipocytes. A molecular docking method was used to preliminarily identify compounds in JLD, which hold the potential activation effect on uncoupling protein 1 (UCP1). JLD treatment significantly improved obesity in db/db mice. Biochemical results showed that JLD reduced blood glucose (GLU), triglyceride (TG), and low-density lipoprotein cholesterol (LDL) levels as well as liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in mice. Hematoxylin and eosin staining (H&E) showed that JLD reduced hepatocyte ballooning changes in the liver. Immunofluorescence showed that JLD increased the expression of the thermogenic protein, UCP1, in the beige adipose tissue of mice. JLD also increased the expression of UCP1 and inhibited the expression of miR-27a in X9 cells. Molecular docking results showed that epmedin B, epmedin C, icariin, puerarin, and salvianolic acid B had potential activation effects on UCP1. The results suggest that JLD may activate beige adipocytes by inhibiting miR-27a expression, thereby promoting thermogenesis in beige adipocytes. This study provides a new pharmacological basis for the clinical use of JLD.

Gestational Diabetes is Associated with an Increased Expression of miR-27a in Peripheral Blood Mononuclear Cells.

Dysregulation of microRNA-based mechanisms is associated with various human pathologies, including gestational diabetes mellitus (GDM), suggesting they may be potential diagnostic and/or prognostic biomarkers of GDM. The expression of miR-340-5p, miR-27a-3p and miR-222-3p in peripheral blood mononuclear cells (PBMCs) obtained from patients with GDM (n=42) and healthy controls (n=34) were evaluated, together with their correlation to the clinical parameters of participants and their newborns. Expression of the selected microRNAs was quantified by quantitative real-time polymerase chain reaction (qPCR), after reverse transcription with microRNA-specific stem-loop primers. The expression of miR-27a-3p was significantly higher in patients with GDM than in controls (p=0.036), whereas no significant difference between groups was found for the other two tested microRNAs. The expression level of miR-27a-3p in GDM patients was found to negatively correlate with the number of erythrocytes, concentration of haemoglobin, haematocrit, and low- and high-density lipoprotein (LDL/HDL) ratio, and positively with the concentration of glycated haemoglobin (HbA1c). In the case of miR-222-3p, a negative correlation between its expression and the concentration of cholesterol, LDL and LDL/HDL ratio was found onlyin healthy pregnant women. The expression level of miR-340-5p negatively correlated with erythrocyte count, haemoglobin concentration and haematocrit in GDM patients, as well as with the concentration of cholesterol, LDL and LDL/HDL ratio in healthy women. The resultsobtained illustrate the potential of PBMC-derived microRNA miR-27a-3p to serve as a diagnostic biomarker of GDM. On the other hand, MiR-27a and miR-340 may help in assessing the metabolic status relevant for pregnancy.

Serum-derived extracellular vesicles mediate Smad4 expression through shuttling microRNA-27a in the progression of laryngeal squamous cell carcinoma.

Serum-derived extracellular vesicles (EVs) containing non-coding RNAs have been indicated to serve as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC), while their functional role remains to be explored. Here, we summarize the possible mechanism explaining the laryngeal carcinogenesis and the associated changes with the involvement of extracellular microRNA (miR)-27a from serum of LSCC patients. Serum-derived EVs from LSCC patients were found to increase the proliferative activity and decreased the apoptotic activity of LSCC cells. miRNA microarrays revealed that miR-27a expression was elevated after EV treatment. miR-27a expression was elevated in LSCC tissues and predicted a poor prognosis for patients. Downregulation of miR-27a inhibited the effect of EVs to reduce the activity of LSCC cells in vitro and to suppress tumor development in vivo. miR-27a targeted SMAD family member 4 (Smad4) to mediate the Wnt/β-catenin pathway, which was induced under the influence of EVs. Smad4 was downregulated in LSCC tissues, and simultaneous overexpression of miR-27a and Smad4 resulted in reduced cell activity and tumorigenicity. In conclusion, serum-derived EVs support the laryngeal carcinogenesis at least partially via transferring miR-27a. miR-27a targets Smad4 and is a biomarker to predict LSCC prognosis.

The association of plasma levels of miR-146a, miR-27a, miR-34a, and miR-149 with coronary artery disease.

Coronary artery disease (CAD) is considered to be one of the most pivotal causes of death in the world. Over the past two decades, significant changes occurred in the diagnosis, prognosis, and treatment of CAD, which has helped reduce mortality rates. microRNAs (miRs) are a class of more than 5000 non-encoding RNA molecules (21-25 nucleotides across the length) that regulate complex biological processes. Today, miRNAs are used to study cardiovascular diseases. In the present study, the expression of miR-146a،miR-27, miR-149, and miR-34a in plasma suffering from CAD and the control group were investigated. The present research was performed on 30 men with CAD and 30 healthy men as controls. The expression levels of miR-146a, miR-27a, miR-149, and miR-34a in the plasma of patients with CAD and the control group were measured using real-time PCR. Also, the correlation between the expression of circulating miRs levels and biochemical LDL-C, HDL-C, BMI, and total cholesterol was evaluated. The expression of miR-27a in the plasma of the CAD group was higher than in the control group (p = 0.020). The expression of miR-146a was downregulated in CAD patients compared to normal subjects (p = 0. 026). However, the expression of miR-34a, miR-149 in the plasma of CAD patients was not significantly different with the control group. In addition to, a direct correlation was found between the expression of miR-146a and HDL-c, the expression of miR-27a and LDL-C and the expression of miR-34a and total cholesterol. Also, the negative correlation between expressions of miR-149 with BMI was reported. The obtained results demonstrated that miRs were closely related to biochemical factors and it points out the fact that miRNAs can be applied as a potential strategy for diagnosis and treatment of CAD.

A functional SNP rs895819 on pre-miR-27a is associated with bipolar disorder by targeting NCAM1

The aberrant expression or genomic mutations of microRNA are associated with several human diseases. This study analyzes the relationship between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 subjects. All these ten SNPs were on or near mature microRNAs. We identified the association between bipolar disorder and the T/C polymorphism at rs895819. To illustrate the function of miR-27a, we constructed several miR-27a knockout (KO) cell lines, determined candidates of miR-27a, and then verified NCAM1 as a target gene of miR-27a. Further studies revealed that the T/C polymorphism on miR-27a led to the differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Furthermore, the C mutation on pre-miR-27a suppresses cell migration and dopamine expression levels. Our study highlights the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.

MicroRNA-30a contributes to pre-eclampsia through regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells by targeting AVEN

ABSTRACT Pre-eclampsia (PE) is a pregnancy-associated disease related to an unprecedented hypertension attack. Mesenchymal stem cells (MSCs) play a crucial role in PE pathology. . Our research was designed to illustrate the functions of microRNA-30a (miR-30a) in proliferation, apoptosis, and the potential of regulating angiogenesis in MSCs, and to analyze its potential molecular mechanisms. TargetScan software and the luciferase reporter assay were used to forecast and verify the relationship between miR-30a and AVEN. MiR-30a and AVEN expression in the decidual tissue and decidua (d)MSCs of healthy pregnant women and PE patients were assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT), flow cytometry, and transwell assays were used to evaluate cell proliferation, growth, the cell cycle, apoptosis, and migration. Furthermore, the tube formation ability was evaluated using the human umbilical vein endothelial cell (HUVEC) tube formation assay. AVEN is the target gene of miR-30a. MiR-30a was upregulated in decidual tissues and dMSCs of PE patients. However, AVEN was weakly expressed, and AVEN expression was negatively related to miR-30a levels in decidual tissues and dMSCs of PE patients. Compared to the mimic control group, upregulation of miR-30a inhibited dMSC proliferation and cell growth, promoted G0/G1 phase arrest, and induced apoptosis. Furthermore, the miR-30a mimic transfected dMSC culture supernatant suppressed HTR-8/SVneo cell migration ability and HUVEC tube formation ability. However, AVEN reversed these changes. In conclusion, miR-30a/AVEN may serve as a new axis for PE treatment.

The Single-Nucleotide Polymorphism of miR-27a rs895819 and the Expression of miR-27a in Helicobacter pylori-Related Diseases and the Correlation with the Traditional Chinese Medicine Syndrome.

Aims The study aims to explore the effects of the single-nucleotide polymorphism of miR-27a and its expression in Helicobacter pylori (H. pylori)-related diseases and the relationship between gastric pathology and traditional Chinese medicine (TCM). Methods Subjects were classified into six histopathological groups and five TCM syndrome groups. All specimens underwent H. pylori detection through rapid urease test and methylene blue staining. Histopathological characteristics were observed by hematoxylin-eosin. The expression of miR-27a and its genotype were, respectively, detected by Quantitative Real-Time PCR and direct sequencing. Results H. pylori promoted the malignant evolution of gastric mucosa and were involved in the formation of TCM syndrome. In H. pylori-positive patients, the frequency of miR-27a CT genotype at the rs895819 locus and its expression in the gastric cancer group were higher than those in other pathological groups. TCM syndrome had a close relationship with histopathological changes, and patients with spleen-qi deficiency syndrome had a higher risk of gastric cancer than other syndromes, regardless of H. pylori infection. Conclusion The C allele at miR-27a rs895819 locus may be an oncogene in gastric cancer. High levels of miR-27a could play an important role in gastric malignant evolution, especially cancerization. There is a certain connection between TCM syndrome and pathological changes of the gastric mucosa to some extent, where patients with SQD syndrome had a higher risk of GC.

MiR-30a targets STOX2 to increase cell proliferation and metastasis in hydatidiform moles via ERK, AKT, and P38 signaling pathways

BackgroundA hydatidiform mole is a condition caused by abnormal proliferation of trophoblastic cells. MicroRNA miR-30a acts as a tumor suppressor gene in most tumors and participates in the development of various cancers. However, its role in hydatidiform moles is not clear.MethodsQuantitative real-time reverse transcription PCR was used to verify the expression level of miR-30a and STOX2 (encoding storkhead box 2). Flow cytometry assays were performed to detect the cell cycle in cell with different expression levels of miR-30a and STOX2. Cell Cycle Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation assays were used to detect cell proliferation and viability. Transwell assays was used to test cell invasion and migration. Dual-luciferase reporter assays and western blotting were used to investigate the potential mechanisms involved.ResultLow miR-30a expression promoted the proliferation, migration, and invasion of trophoblastic cells (JAR and HTR-8). Dual luciferase assays confirmed that STOX2 is a target of miR-30a and resisted the effect of upregulated miR-30a in trophoblastic cells. In addition, downregulation of STOX2 by miR-30a could activate ERK, AKT, and P38 signaling pathways. These results revealed a new mechanism by which ERK, AKT, and P38 activation by miR-30a/STOX2 results in excessive proliferation of trophoblast cells in the hydatidiform mole.ConclusionsIn this study, we found that miR-30a plays an important role in the development of the hydatidiform mole. Our findings indicate that miR-30a might promote the malignant transformation of human trophoblastic cells by regulating STOX2, which strengthens our understanding of the role of miR-30a in regulating trophoblastic cell transformation.

Natural Plant Compounds: Does Caffeine, Dipotassium Glycyrrhizinate, Curcumin, and Euphol Play Roles as Antitumoral Compounds in Glioblastoma Cell Lines?

Many plant-derived compounds are shown to be promising antitumor therapeutic agents by enhancing apoptosis-related pathways and cell cycle impairment in tumor cells, including glioblastoma (GBM) cell lines. We aimed to review four natural plant compounds effective in GBM cell lines as caffeine, dipotassium glycyrrhizinate (DPG), curcumin, and euphol. Furthermore, antitumoral effect of these plant compounds on GBM cell lines through microRNAs (miRs) modulation was investigated. However, only DPG and curcumin were found as effective on miR modulation. Caffeine arrests GBM cell cycle in G0/G1 phase by cyclin-dependent kinases (CDK) complex inhibition and by decreasing BCL-2 and increasing FOXO1 expression levels causing greater apoptotic activity. Caffeine can also directly inhibit IP3R3, p38 phosphorylation, and rho-associated protein kinase (ROCK), decreasing cell invasion and migration capacity or indirectly by inhibiting the tissue inhibitor metalloproteinase-1 (TIMP-1) and integrins β1 and β3, leading to lower matrix metalloproteinases, MMP-2 and MMP-9. DPG presents antitumoral effect in GBM cells related to nuclear factor kappa B (NF-κB) pathway suppression by IRAK2 and TRAF6-mediating miR-16 and miR-146a, respectively. More recently, it was observed that DPG upregulated miR-4443 and miR-3620, responsible for post-transcriptional inhibition of the NF-κB pathway by CD209 and TNC modulation, respectively leading to lower MMP-9 and migration capacity. Curcumin is able to increase miR-223-3p, miR-133a-3p, miR-181a-5p, miR-34a-5p, miR-30c-5p, and miR-1290 expression leading to serine or threonine kinase (AKT) pathway impairment and also it decreases miR-27a-5p, miR-221-3p, miR-21-5p, miR-125b-5p, and miR-151-3p expression causing p53-BCL2 pathway inhibition and consequently, cellular apoptosis. Interestingly, lower expression of miR-27a by curcumin action enhanced the C/EBP homologous protein(CHOP) expression, leading to paraptosis. Curcumin can inhibit miR-21 expression and consequently activate apoptosis through caspase 3 and death receptor (DR) 4 and 5 activation. Autophagy is controlled by the LC-3 protein that interacts with Atg family for the LC3-II formation and autophagy activation. Euphol can enhance LC3-II levels directly in GBM cells or inhibits tumor invasion and migration through PDK1 modulation.

Clinical Significance of MiR-27a Expression in Serum Exosomes in Patients with Heart Failure.

To study the clinical significance of miR-27a expression in serum exosomes in patients with heart failure (HF), this study was carried out. Totally 101 chronic heart failure (CHF) patients (research group) admitted to our hospital from April 2016 to January 2019 were enrolled, and another 30 healthy subjects (control group) who underwent physical examination during the same period were selected. The difference of miR-27a expression level in serum exosomes between the two groups of subjects was compared, so as to analyze the diagnostic value of miR-27a in CHF and the relationship between miR-27a expression level and patient prognosis. The expression level of miR-27a in peripheral blood exosomes of subjects in the control group (CG) was significantly higher than that in the research group (RG) (P<0.05), while the miR-27a expression of the latter increased significantly 3 months after treatment (P<0.05). ROC analysis showed that the AUC, sensitivity, specificity, and critical level of miR-27a in the diagnosis of CHF were 0.835, 77.23%, 80.00%, and 1.060 respectively. While after 3 months of treatment, the indicators of the RG effectively improved (P<0.05). Pearson and Sparman correlation analysis revealed that there was a significant linear correlation between miR-27a and each indicator (P<0.05). K-M survival curve analysis demonstrated that the survival rate of patients with high expression of miR-27a was significantly higher than that of patients with low expression (P<0.05). The expression of mR-27a in serum exosomes is decreased in patients with HF and has important potential value in the diagnosis and prognosis of CHF.

Myocardin/microRNA-30a/Beclin1 signaling controls the phenotypic modulation of vascular smooth muscle cells by regulating autophagy

Upon vascular injury, vascular smooth muscle cells (VSMCs) change from a contractile phenotype to a synthetic phenotype, thereby leading to atherogenesis and arterial restenosis. Myocardin (MYOCD) is essential for maintaining the contractile phenotype of VSMCs. Deletion of MYOCD in VSMCs triggers autophagy. However, the molecular mechanism underlying the effect of MYOCD on autophagy is not clear. In this study, knockdown of MYOCD in human aortic VSMCs (HA-VSMCs) triggered autophagy and diminished the expression of SMC contractile proteins. Inhibition of autophagy in MYOCD-knockdown cells restored the expression of contractile proteins. MYOCD activated the transcription of miR-30a by binding to the CArG box present in its promoter, as confirmed by luciferase reporter and chromatin immune coprecipitation assays, while miR-30a decreased the expression of autophagy protein-6 (ATG6, also known as beclin1) by targeting its 3′UTR. Restoring the expression of miR-30a in MYOCD-knockdown cells upregulated the levels of contractile proteins. Treatment of VSMCs with platelet-derived growth factor type BB (PDGF-BB) resulted in the transformation of VSMCs to a proliferative phenotype. A low level of miR-30a was observed in PDGF-BB-treated HA-VSMCs, and re-expression of miR-30a led to a decrease in proliferative marker expression. Furthermore, using a wire injury mouse model, we found that miR-30a expression was significantly downregulated in the arterial tissues of mice and that restoration of miR-30a expression at the injured site abolished neointimal formation. Herein, MYOCD could inhibit autophagy by activating the transcription of miR-30a and that miR-30a-mediated autophagy defects could inhibit intimal hyperplasia in a carotid arterial injury model.

CircTMOD3 promotes lipopolysaccharide-induced chondrocyte apoptosis in osteoarthritis by sponging miR-27a

The progression of osteoarthritis (OA) requires the involvement of lipopolysaccharide (LPS)-induced inflammation, in which circTMOD3 plays an important role. We predicted that circTMOD3 could interact with miR-27a to inhibit LPS-induced chondrocyte apoptosis and explored the interaction between circTMOD3 and miR-27a in OA. Total RNAs were isolated from cartilage tissue samples from both OA patients (n = 62) and controls (n = 62) and subjected to RT-qPCRs to determine circTMOD3 and miR-27a (mature and premature) expression. Subcellular location of circTMOD3 and its interaction with premature miR-27a were analyzed using subcellular fractionation assay and RNA-RNA pulldown assay, respectively. CircTMOD3 was overexpressed in chondrocytes to study its role in miR-27a maturation. The roles of circTMOD3 and miR-27a in LPS-induced chondrocyte apoptosis were analyzed using cell apoptosis assay. CircTMOD3 and premature miR-27a levels were increased while mature miR-27a level was decreased in OA. CircTMOD3 was located in both nuclear and cytoplasm fractions of chondrocytes. CircTMOD3 directly interacted with premature miR-27a and promoted LPS-induced chondrocyte apoptosis, while miR-27a inhibited LPS-induced chondrocyte apoptosis. Moreover, circTMOD3 overexpression suppressed miR-27a maturation and reduced the inhibitory effects of miR-27a on LPS-induced chondrocyte apoptosis. CircTMOD3 suppresses miR-27a maturation in OA to promote chondrocyte apoptosis induced by LPS.

P029 Expression of miR-21 in mucosal biopsies give clues to anti-TNF treatment non-response in IBD children and adults

Abstract Background The use of anti-tumor necrosis factor (TNF) treatment has improved the treatment of IBD patients. However, approximately 30% of patients fail to respond to TNF inhibitors, and up to 50% of the patients who initially benefited from treatment with TNF inhibitors lose the response over time. Thus, identifying predictors of non-response and deciding on a treatment strategy according to biomarker profiles could enhance overall IBD disease management. MicroRNA-21 (miR-21) has been found to confer drug resistance to e.g. trastuzumab, 5-fluorouracil, and cisplatin. In this study, we hypothesized that miR-21 may play a role in anti-TNF drug resistance and therefore, miR-21 levels may be a predictive biomarker of anti TNF response in IBD. Methods Archived formalin-fixed, paraffin-embedded (FFPE) mucosal biopsies of IBD patients (30 adults and 27 children) were used in this study. All biopsies were collected at the time of initiation of biologics. Patients were stratified into three groups according to treatment response: Responders, Primary non-responders (PNR), and Secondary non-responders (SNR). Responders were treated with anti-TNF for a minimum of 3 years and did not experience loss of response thereafter. PNRs lost response during the first year of treatment. SNRs were treated for a minimum of 3 years with subsequent loss of response. MiR-21 expressions were quantified using Quantitative Real-Time PCR (miRCURY LNA RT Kit, Qiagen). Expression of miR-27a was used as the endogenous reference microRNA based on previous studies. Results In adults, responders had less miR-21 expression compared to PNRs and SNRs (relative median of miR-21 expression in folds [IQR]: 3.45[3.36 - 4.2], 5.05 [3.61 - 6.88], and 7.58 [6.21 - 8.2] in responders, PNRs, and SNRs respectively, p=0.04 and p=&amp;lt;0.01). In children, however, responders had an increased miR-21 expression compared to PNRs and SNRs (relative median of miR-21 expression in folds [IQR]: 19.94[15.88–24.59], 9.79[7.69– 14.44], and 10.58[5.66–12.91] in responders, PNRs, and SNRs respectively, p=0.03 and p=0.01). Expression of MiR-21 was found to be higher in children than adults (relative median of miR-21 expression in folds [IQR]: 4.65[3.45–7.21], and 13.6[8.37–19.05], respectively, p=&amp;lt;0.01). Conclusion Higher miR-21 expression indicates a higher response rate in children, whereas higher miR-21 expression could predict resistance to anti-TNF treatment in adults. MiR-21 expression could potentially be used as a predictive biomarker for anti-TNF treatment response in IBD patients with varying measures for children and adults.

Eight weeks of combined exercise training do not alter circulating microRNAs-29a, -133a, -133b, and -155 in young, healthy men.

Individuals with a family history of type 2 diabetes (FH +) have an increased risk of developing type 2 diabetes. Circulating microRNAs (miRNAs) have been implicated as biomarkers of type 2 diabetes risk. Here, we investigated if four circulating miRNAs related to glucose metabolism were altered in men with a FH + and we conducted a preliminary analysis to determine if miRNA expressions were responsive to 8 weeks of combined exercise training. Sixteen young healthy men (mean ± SD; age 22.5 ± 2.5; BMI 26.4 ± 4.0) with FH + or without a family history of type 2 diabetes (FH -) underweight 8 weeks of combined endurance and resistance exercise training (n = 8 FH -; n = 8 FH +). The expression of miR-29a, miR-133a, miR-133b, and miR-155 were measured in serum before and after exercise training. QIAGEN's Ingenuity® Pathway Analysis was used to examine miRNA target genes and their involvement in glucose metabolism signaling pathways. There were no differences in miRNA expressions between FH - and FH + . Exercise training did not alter miRNA expressions in either FH - or FH + despite improvements in insulin sensitivity, aerobic capacity, and muscular strength. miR-29a and miR-155 were inversely related to fasting glucose, and miR-133a and miR-133b were negatively correlated with glucose tolerance; however, correlations were not observed with insulin sensitivity. The circulating miRNAs- miR-29a, miR-133a, miR-133b, and miR-155 are related to measures of glucose metabolism in healthy, normoglycemic men, but do not reflect peripheral insulin sensitivity or improvements in metabolic health following 8 weeks of combined exercise training.

MiR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy

BackgroundAccumulating evidence has revealed that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. Emerging evidence has demonstrated that miR-133a participates in the tumorigenesis of various cancers. However, whether miR-133a is associated with cisplatin resistance in ovarian cancer remains unclear.ObjectiveTo investigate the role of miR-133a in the development of cisplatin resistance in ovarian cancer.MethodsMiR-133a expression in cisplatin-resistant ovarian cancer cell lines was assessed by reverse-transcription quantitative PCR (RT–qPCR). A cell counting kit-8 (CCK-8) assay was used to evaluate the viability of tumour cells treated with cisplatin in the presence or absence of miR-133a. A luciferase reporter assay was used to analyse the binding of miR-133a with the 3′ untranslated region (3′UTR) of YES proto-oncogene 1 (YES1). The YES1 expression level was analysed using a dataset from the International Cancer Genome Consortium (ICGC) and assessed by RT–qPCR and western blotting in vitro. The roles and mechanisms of YES1 in cell functions were further probed via gain- and loss-of-function analysis.ResultsThe expression of miR-133a was significantly decreased in cisplatin-resistant ovarian cancer cell lines (A2780-DDP and SKOV3-DDP), and the overexpression of the miR-133a mimic reduced cisplatin resistance in A2780-DDP and SKOV3-DDP cells. Treatment with the miR-133a inhibitor increased cisplatin sensitivity in normal A2780 and SKOV3 cells. MiR-133a binds the 3’UTR of YES1 and downregulates its expression. Bioinformatics analysis revealed that YES1 expression was upregulated in recurrent cisplatin-resistant ovarian cancer tissue, and in vitro experiments also verified its upregulation in cisplatin-resistant cell lines. Furthermore, we discovered that miR-133a downregulated the expression of YES1 and thus inhibited cell autophagy to reduce cisplatin resistance. Yes1 knockdown significantly suppressed the cisplatin resistance of ovarian cancer cells by inhibiting autophagy in vitro. Xenograft tumour implantation further demonstrated that Yes1 overexpression promoted ovarian tumour development and cisplatin resistance.ConclusionsOur results suggest that the miR-133a/YES1 axis plays a critical role in cisplatin resistance in human ovarian cancer by regulating cell autophagy, which might serve as a promising therapeutic target for ovarian cancer chemotherapy treatment in the future.

MiR-30a Serves as a Tumor Suppressor for Hepatocellular Carcinoma by Downregulating ADAMTS14.

Hepatocellular carcinoma (HCC) is a very common malignancy in the world, but the effect of therapies on advanced HCC has not improved for decades. The present study aimed to investigate the role of miR-30a in the tumorigenesis of HCC. The expression of miR-30a and ADAMTS14 in HCC tissues were determined. Luciferase reporter gene detection confirmed the correlation between miR-30a and ADAMTS14. Cell viability and apoptosis rate were examined using an MTT assay and flow cytometry. Cell migration and invasion ability were detected by a transwell assay. The protein expression of ADAMTS14, β-catenin, GSK-3β, and p-GSK-3β were determined using western blotting. miR-30a was negatively correlated with the expression of ADAMTS14 in HCC tissues. Further research confirmed that ADAMTS14 is the direct target of miR-30a. In addition, the expression of ADAMTS14, cell viability and apoptosis were suppressed by miR-30a overexpression, while knockdown of miR-30a led to the opposite result. miR-30a also inhibits the phosphorylation of GSK-3β and β-catenin, without changing the total GSK-3β level. miR-30a acts as a tumor suppressor in the progression of HCC and can be used as a biomarker for early prediction and diagnosis.

The oncogenic miR-27a/BTG2 axis promotes obesity-associated hepatocellular carcinoma by mediating mitochondrial dysfunction.

Obesity is closely related to the initiation and development of hepatocellular carcinoma (HCC). The regulatory mechanism of obesity-associated HCC remains unclear. HepG2 cells treated with palmitic acid (PA) and diethylnitrosamine (DEN)-induced HCC mice fed a high-fat diet (HFD) were established. The expression of miR-27a and B-cell translocation gene 2 (BTG2) mRNA and protein were detected via qPCR and western blotting. Prediction software and luciferase assays were employed to verify the miR-27a/BTG2 axis. The biological effects of HepG2 cells were evaluated with ORO staining, MTT assays, Transwell assays, Mito-Timer, and Mito-SOX staining. Significantly upregulated miR-27a and downregulated BTG2 mRNA and protein were observed in HepG2 cells and liver tissues of HCC mice. Overexpressing miR-27a (mi-miR-27a) markedly promoted cellular lipid accumulation, proliferation, and invasion, accompanied by aggravated mitochondrial dysfunction (increased fading and ROS products of mitochondria) in HepG2 cells. Additionally, these effects were further reinforced in HepG2 cells treated with mi-miR-27a and PA. BTG2 was identified as a direct target and was negatively regulated by miR-27a. Similarly, BTG2 knockdown (sh-BTG2) had effects identical to those of mi-miR-27a on HepG2 cells. Additionally, PA evidently enhanced these effects of sh-BTG2 in HepG2 cells. Moreover, BTG2 overexpression effectively reversed the effects of miR-27a, including lipotropic and oncogenic effects, and simultaneously promoted mitochondrial imbalance in HepG2 cells. Thus, obesity-associated miR-27a acts as an oncogene to promote lipid accumulation, proliferation, and invasion by negatively regulating BTG2-mediated mitochondrial dysfunction in HCC.

The potential use of miRNAs in the diagnosis and prediction of metastatic lung carcinoma.

Lung carcinoma is the "top killer" of all malignancies in the world. Early diagnosis of lung carcinoma significantly improves patient survival. Screening with biomarkers from peripheral blood could detect more patients at an early stage of the disease. MicroRNAs (miRNAs) could be a possible biomarker. These are 21-23 nucleotide long single-stranded RNA molecules playing an important role in the post-transcriptional regulation of gene activity. Individual miRNAs have the potential to regulate genes responsible for cell proliferation, differentiation, apoptosis, regulate cell cycle in cooperation with pro-oncogenes and tumor suppressor genes. In our study, we determined miRNA expression levels in individual samples of lung carcinoma patients and in a healthy control group. We used the reverse transcription method followed by qRT-PCR. The expression levels of the investigated miRNAs were evaluated in the QIAGEN GeneGlobe Data center software. We demonstrated the significance of miR-126 and let-7g as biomarkers of lung carcinoma in all clinical stages studied. We also observed significantly increased expression of miR-143 and miR-145 at the distant metastasis stage, and significantly decreased expression of miR-133a in the N2 disease group of lung carcinoma patients (N2 disease represents disease with metastases in the ipsilateral mediastinal and/or subcarinal lymph nodes or node). The investigated miRNAs showed no clear potential for detecting potentially resectable (N0-N1), locally advanced (N2) and distant organ metastatic (M1) lung carcinoma.