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Purpose: This study explored the clinical value of long non-coding RNA small nucleolar RNA host gene 14 (SNHG14) in diabetic kidney disease (DKD) and the mechanism of renal tubular injury., Methods: Patients with DKD, type 2 diabetes mellitus (T2DM) and healthy individuals (HVs) were included, as well as the human proximal tubular epithelial cell line (HK-2) induced by high glucose was also included. The mRNA levels of SNHG14 in the serum and cells were detected using RT-qPCR. Diagnostic significance was examined using receiver operating characteristic (ROC) analysis. A commercial test kit, flow cytometry, and enzyme-linked immunosorbent assays were employed to assess reactive oxygen species (ROS) production, apoptosis, inflammatory factor secretion, and extracellular matrix protein levels in HK-2 cells. The dual-luciferase reporter assay and RNA immunoprecipitation were used to validate miR-483-5p concerning SNHG14 or histone deacetylase 4 (HDAC4)., Results: SNHG14 and HDAC4 levels were elevated in the serum of DKD patients and HG-induced HK-2 cells, while miR-483-5p levels were decreased (P < 0.001). SNHG14 increased HDAC4 levels by sponging miR-483-5p. Elevated SNHG14 levels significantly differentiated DKD patients from HVs (AUC = 0.944) and T2DM (AUC = 0.867). Silencing of SNHG14 alleviated HG-induced ROS production and apoptosis as well as the over-secretion of inflammatory factors and extracellular matrix proteins; however, this alleviation was typically suppressed by low expression of miR-483-5p (P < 0.001). Elevated miR-483-5p alleviates HG-induced renal tubular injury, but this alleviation is suppressed by HDAC4 overexpression., Conclusion: In summary, suppression of SNHG14 has been shown in our study to mitigate renal tubular injury in DKD by regulating apoptosis, oxidative stress, inflammation, and fibrosis through the miR-483-5p/HDAC4 axis., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Aim: To assess the expression and function of miR-483-5p in diabetic β cells., Methods: The expression of miR-483-5p was evaluated in the pancreatic islets of obesity mouse models by quantitative reverse transcription polymerase chain reaction. Dual-luciferase activity, and western blotting assays, were utilized for miR-483-5p target gene verification. Mice with β cell-specific miR-483-5p downregulation were studied under metabolic stress (i.e. a high-fat diet) condition. Lineage tracing was used to determine β-cell fate., Results: miR-483-5p increased in the islets of obese mouse models. Expression levels of miR-483-5p were significantly upregulated with the treatment of high glucose and palmitate, in both MIN6 cells and mouse islets. Overexpression of miR-483-5p in β cells results in impaired insulin secretion and β-cell identity. Cell lineage-specific analyses revealed that miR-483-5p overexpression deactivated β-cell identity genes (insulin, Pdx1 and MafA) and derepressed β-cell dedifferentiation (Ngn3) genes. miR-483-5p downregulation in β cells of high-fat diet-fed mice alleviated diabetes and improved glucose intolerance by enhancing insulin secretory capacity. These detrimental effects of miR-483-5p relied on its seed sequence recognition and repressed expression of its target genes Pdx1 and MafA, two crucial markers of β-cell maturation., Conclusions: These findings indicate that the miR-483-5p-mediated reduction of mRNAs specifies β-cell identity as a contributor to β-cell dysfunction via the loss of cellular differentiation., (© 2024 John Wiley & Sons Ltd.)

Objectives: Periodontitis is induced by the imbalance between osteoblast and osteoclast activity, which leads to periodontal tissue destruction. Macrophages play a vital role in periodontitis. However, the hypoxic periodontal environment will also induce macrophage apoptosis within a short time. Apoptotic bodies (ABs) are the major products generated from apoptotic cells, but whether macrophage-derived ABs play a regulatory role as their mother cells in periodontitis remains unknown. In the present study, we aimed to investigate the effects of ABs on osteoblasts., Method: ABs derived from hypoxia-induced macrophages were co-cultured with osteoblasts and the impact of ABs on osteoblast differentiation in vitro was assessed. In vivo, periodontitis model was established and macrophages-derived ABs were injected into the gingival sulcus. The effects of ABs on periodontal bone resorption were determined., Results: The results showed that ABs significantly inhibit osteoblast differentiation and promoted alveolar bone resorption in periodontitis. MicroRNA (miRNAs) array analysis was performed and revealed that miR-483-5p is the key miRNA in ABs. Dual luciferase reporter assays were performed and confirmed that miR-483-5p targeted Col1A1 mRNA and attenuated its expression., Conclusion: Macrophage-derived ABs inhibit osteoblast differentiation via the transfer of miR-483-5p, which downregulates Col1A1 expression and finally suppresses osteogenic activity., (© 2023 Wiley Periodicals LLC.)

Astrocytes are in constant communication with neurons during the establishment and maturation of functional networks in the developing brain. Astrocytes release extracellular vesicles (EVs) containing microRNA (miRNA) cargo that regulates transcript stability in recipient cells. Astrocyte released factors are thought to be involved in neurodevelopmental disorders. Healthy astrocytes partially rescue Rett Syndrome (RTT) neuron function. EVs isolated from stem cell progeny also correct aspects of RTT. EVs cross the blood-brain barrier (BBB) and their cargo is found in peripheral blood which may allow non-invasive detection of EV cargo as biomarkers produced by healthy astrocytes. Here we characterize miRNA cargo and sequence motifs in healthy human astrocyte derived EVs (ADEVs). First, human induced Pluripotent Stem Cells (iPSC) were differentiated into Neural Progenitor Cells (NPCs) and subsequently into astrocytes using a rapid differentiation protocol. iPSC derived astrocytes expressed specific markers, displayed intracellular calcium transients and secreted ADEVs. miRNAs were identified by RNA-Seq on astrocytes and ADEVs and target gene pathway analysis detected brain and immune related terms. The miRNA profile was consistent with astrocyte identity, and included approximately 80 miRNAs found in astrocytes that were relatively depleted in ADEVs suggestive of passive loading. About 120 miRNAs were relatively enriched in ADEVs and motif analysis discovered binding sites for RNA binding proteins FUS, SRSF7 and CELF5. miR-483-5p was the most significantly enriched in ADEVs. This miRNA regulates MECP2 expression in neurons and has been found differentially expressed in blood samples from RTT patients. Our results identify potential miRNA biomarkers selectively sorted into ADEVs and implicate RNA binding protein sequence dependent mechanisms for miRNA cargo loading., Competing Interests: Declaration of competing interest The authors declare they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Diabetic retinopathy (DR) is a progressive disease which can cause health problem. It has been reported that bone marrow mesenchymal stem cells (BMSCs)-secreted exosomes could regulate the progression of DR via carrying microRNAs. Meanwhile, miR-483-5p was downregulated in DR; however, whether BMSCs-secreted exosomes can modulate DR progression via carrying miR-483-5p remains unclear. To mimic DR in vitro, ARPE-19 cells were exposed to 30 mM high glucose (HG). Exosomes were isolated from BMSCs and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Cell counting kit-8 assay was applied for assessing the cell viability. Flow cytometry was applied to test the cell apoptosis. Meanwhile, dual luciferase assay was used to evaluate the association among miR-483-5p and downstream target insulin-like growth factor 1 receptor (IGF-1R). In addition, quantitative reverse-transcription polymerase chain reaction and western blot were used for exploring the level of miR-483-5p and IGF-1R. HG significantly induced apoptosis in ARPE-19 cells, while BMSCs-derived exosomes reversed this phenomenon. In addition, inhibition of miR-483-5p expression of exosomes further aggravated HG-induced ARPE-19 cell apoptosis. Meanwhile, IGF-1R was the downstream messenger RNA of miR-483-5p, and IGF-1R silencing could reverse the effect of exosomes with downregulated miR-483-5p on HG-induced cell injury. Exosomes derived from BMSCs inhibit the progression of DR via carrying miR-483-5p. Thus, our study might provide a theoretical basis for discovering new strategies against DR., (© 2023 Wiley Periodicals LLC.)

Background: Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression., Methods: GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients., Results: The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p's engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes., Conclusion: This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement of up-to-date treatment protocols, the survival rates of Wilms tumor have increased. However, metastases or local relapses are still observed in 15% of patients. The search for reliable biomarkers to identify at-risk patients is ongoing to predict the variability in treatment success. Currently, the evaluation of clinical, histopathological and genetic features are common diagnostic methods; however, epigenetic features can be examined with microRNA expression analyses and might allow us to comment on the behavior of the tumor and treatment response., Methods: In this study, we aimed to evaluate the relationship between microRNA-204 and microRNA-483-5p expression with clinicopathological data and the effect on Wilms tumor survival. For this purpose, the expression levels of RNU6B, microRNA-204 and microRNA-483-5p were evaluated in tumor and normal tissue by qreal time-polymerase chain reaction. We also investigated the relationship between microRNA expression levels with the clinicopathological and histological features of Wilms tumor., Results and Conclusion: The results of our study indicate that the relative expression levels of microRNA-204 in Wilms tumor tissues were significantly lower than that in adjacent normal tissues. By contrast, tumor tissue had a higher microRNA-483-5p expression than the corresponding normal tissues. A statistically significant difference between microRNA-204 expression level with age and the presence of anaplasia was observed. The upregulation of microRNA-483-5p was found to have a significant correlation with patients after preoperative chemotherapy and complete tumor necrosis. Taken together, our data suggest that microRNA-204 could play a critical role as a tumor suppressor, whereas microRNA-483-5p acts as an oncogene in Wilms tumor progression. More importantly, microRNA-204 might be a novel predictive biomarker for anaplastic histology and could be useful for developing therapeutic interventions targeting this marker., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In light of the abnormal expression of microRNA (miR-483-5p) in patients with atherosclerosis (AS), its role in vascular endothelial cell injury was explored. And the mechanisms related to autophagy were also elucidated., Methods: Human umbilical vein endothelial cells (HUVECs) were given 100 mg/L ox-LDL to induce endothelial injury. Cell transfection was done to regulate miR-483-5p levels. Cell viability and apoptosis were detected. qRT-PCR was employed for the mRNA levels' detection., Results: Autophagic flux impairment of HUVECs was detected after ox-LDL treatment, along with the upregulation of miR-483-5p. Ox-LDL inhibited cell viability and promoted cell apoptosis, but these influences were changed by miR-483-5p downregulation. MiR-483-5p downregulation decreased the mRNA levels of IL-1β, IL-6, ICAM-1 and VCAM-1. 3-MA, the autophagy inhibitor, reversed the beneficial role of miR-483-5p downregulation in ox-LDL-induced HUVECs' injury. TIMP2 acts as a target gene of miR-483-5p, and was downregulated in HUVEC models., Conclusion: MiR-483-5p downregulation alleviated ox-LDL-induced endothelial injury via activating autophagy, this might be related to TIMP2., (© 2023. The Author(s).)

Background: MicroRNA (miRNA) plays a critical function in the progression of acute coronary syndrome (ACS) and is associated with major adverse cardiovascular events (MACEs) after undergoing percutaneous coronary intervention (PCI). This research was designed to probe the diagnostic accuracy of miR-483-5p in patients with ACS and its predictive value of MACEs., Methods: 118 patients with ACS (40 with unstable angina pectoris [UAP] and 78 with acute myocardial infarction [AMI]) and 75 healthy controls were enrolled. Serum miR-483-5p was detected in the subjects by reverse transcription-quantitative real-time PCR (RT-qPCR). ROC curve and logistic regression models were employed to estimate the diagnosis. Patients were monitored for 6 months after PCI to document the occurrence of MACEs. Kaplan-Meier survival was conducted to explore the predictive significance of miR-483-5p for the MACEs., Results: Serum miR-483-5p levels were higher in ACS patients and associated with SYNTAX score and Gensini score. miR-483-5p was effective in identifying ACS patients from healthy individuals (AUC = 0.919) and AMI patients from ACS patients (AUC = 0.867), demonstrating a high diagnostic value, proven by logistic regression (OR = 9.664, 95%CI = 4.462-20.928, P < 0.001). The prevalence of MACEs during follow-up were 24.58%, and a higher prevalence of MACEs were observed in patients with elevated miR-483-5p (P = 0.01). miR-483-5p was also an effective predictor of MACE occurrence (HR = 5.955, 95%CI = 1.928-18.389, P = 0.002)., Conclusion: Expression of serum miR-483-5p can be utilized as a non-invasive marker for diagnosing ACS and predicting the onset of MACE after PCI., (© 2023. The Author(s).)

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI., (© 2022. The Author(s).)

MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression by targeting specific messenger RNAs (mRNAs) in distinct cell types. This review provides a com-prehensive overview of the current understanding regarding the involvement of miR-483-5p and miR-483-3p in various physiological and pathological processes. Downregulation of miR-483-5p has been linked to numerous diseases, including type 2 diabetes, fatty liver disease, diabetic nephropathy, and neurological injury. Accumulating evidence indicates that miR-483-5p plays a crucial protective role in preserving cell function and viability by targeting specific transcripts. Notably, elevated levels of miR-483-5p in the bloodstream strongly correlate with metabolic risk factors and serve as promising diagnostic markers. Consequently, miR-483-5p represents an appealing biomarker for predicting the risk of developing diabetes and cardiovascular diseases and holds potential as a therapeutic target for intervention strategies. Conversely, miR-483-3p exhibits significant upregulation in diabetes and cardiovascular diseases and has been shown to induce cellular apoptosis and lipotoxicity across various cell types. However, some discrepancies regarding its precise function have been reported, underscoring the need for further investigation in this area.

Coronary artery disease (CAD) is the leading cause of mortality worldwide. In chronic and myocardial infarction (MI) states, aberrant levels of circulating microRNAs compromise gene expression and pathophysiology. We aimed to compare microRNA expression in chronic-CAD and acute-MI male patients in peripheral blood vasculature versus coronary arteries proximal to a culprit area. Blood from chronic-CAD, acute-MI with/out ST segment elevation (STEMI/NSTEMI, respectively), and control patients lacking previous CAD or having patent coronary arteries was collected during coronary catheterization from peripheral arteries and from proximal culprit coronary arteries aimed for the interventions. Random coronary arterial blood was collected from controls; RNA extraction, miRNA library preparation and Next Generation Sequencing followed. High concentrations of microRNA-483-5p (miR-483-5p) were noted as 'coronary arterial gradient' in culprit acute-MI versus chronic-CAD ( p = 0.035) which were similar to controls versus chronic-CAD ( p < 0.001). Meanwhile, peripheral miR-483-5p was downregulated in acute-MI and chronic-CAD, compared with controls (1.1 ± 2.2 vs. 2.6 ± 3.3, respectively, p < 0.005). A receiver operating characteristic curve analysis for miR483-5p association with chronic CAD demonstrated an area under the curve of 0.722 ( p < 0.001) with 79% sensitivity and 70% specificity. Using in silico gene analysis, we detected miR-483-5p cardiac gene targets, responsible for inflammation ( PLA2G5 ), oxidative stress ( NUDT8 , GRK2 ), apoptosis ( DNAAF10 ), fibrosis ( IQSEC2 , ZMYM6 , MYOM2 ), angiogenesis ( HGSNAT , TIMP2 ) and wound healing ( ADAMTS2 ). High miR-483-5p 'coronary arterial gradient' in acute-MI, unnoticed in chronic-CAD, suggests important local mechanisms for miR483-5p in CAD in response to local myocardial ischemia. MiR-483-5p may have an important role as a gene modulator for pathologic and tissue repair states, is a suggestive biomarker, and is a potential therapeutic target for acute and chronic cardiovascular disease.

Inadequate osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are key factors in the pathogenesis of osteoporosis. Patients with Alzheimer's disease (AD) have a higher incidence of osteoporosis than healthy adults, but the underlying mechanism is not clear. Here, we show that brain-derived extracellular vesicles (EVs) from adult AD or wild-type mice can cross the blood-brain barrier to reach the distal bone tissue, while only AD brain-derived EVs (AD-B-EVs) significantly promote the shift of the BMSC differentiation fate from osteogenesis to adipogenesis and induce a bone-fat imbalance. MiR-483-5p is highly enriched in AD-B-EVs, brain tissues from AD mice, and plasma-derived EVs from AD patients. This miRNA mediates the anti-osteogenic, pro-adipogenic, and pro-osteoporotic effects of AD-B-EVs by inhibiting Igf 2. This study identifies the role of B-EVs as a promoter of osteoporosis in AD by transferring miR-483-5p., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

MicroRNAs (miRNAs) are small non-coding RNA molecules that bind with the 3' untranslated regions (UTRs) of genes to regulate expression. Downregulation of miR-483-5p (miR-483) is associated with the progression of hepatocellular carcinoma (HCC). However, the significant roles of miR-483 in nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD), and HCC remain elusive. In the current study, we investigated the biological significance of miR-483 in NAFLD, AFLD, and HCC in vitro and in vivo. The downregulation of miR-483 expression in HCC patients' tumor samples was associated with Notch 3 upregulation. Overexpression of miR-483 in a human bipotent progenitor liver cell line HepaRG and HCC cells dysregulated Notch signaling, inhibited cell proliferation/migration, induced apoptosis, and increased sensitivity towards antineoplastic agents sorafenib/regorafenib. Interestingly, the inactivation of miR-483 upregulated cell steatosis and fibrosis signaling by modulation of lipogenic and fibrosis gene expression. Mechanistically, miR-483 targets PPARα and TIMP2 gene expression, which leads to the suppression of cell steatosis and fibrosis. The downregulation of miR-483 was observed in mice liver fed with a high-fat diet (HFD) or a standard Lieber-Decarli liquid diet containing 5% alcohol, leading to increased hepatic steatosis/fibrosis. Our data suggest that miR-483 inhibits cell steatosis and fibrogenic signaling and functions as a tumor suppressor in HCC. Therefore, miR-483 may be a novel therapeutic target for NAFLD/AFLD/HCC management in patients with fatty liver diseases and HCC.

Purpose: Meningioma is the most common primary central nervous system tumor often causing serious complications, and presently no medical treatment is available. The goal of this study was to discover miRNAs dysregulated in meningioma, and explore miRNA-associated pathways amenable for therapeutic interventions., Methods: Small RNA sequencing was performed on meningioma tumor samples to study grade-dependent changes in microRNA expression. Gene expression was analyzed by chromatin marks, qRT-PCR and western blot. miRNA modulation, anti-IGF-2 neutralizing antibodies, and inhibitors against IGF1R were evaluated in a tumor-derived primary cultures of meningioma cells., Results: Meningioma tumor samples showed high, grade-dependent expression of miR-483-5p, associated with high mRNA and protein expression of its host gene IGF-2. Inhibition of miR-483-5p reduced the growth of cultured meningioma cells, whereas a miR-483 mimic increased cell proliferation. Similarly, inhibition of this pathway with anti-IGF-2 neutralizing antibodies reduced meningioma cell proliferation. Small molecule tyrosine kinase inhibitor blockade of the IGF-2 receptor (IGF1R) resulted in rapid loss of viability of cultured meningioma tumor-derived cells, suggesting that autocrine IGF-2 feedback is obligatory for meningioma tumor cell survival and growth. The observed IGF1R-inhibitory IC50 for GSK1838705A and ceritinib in cell-based assays along with the available pharmacokinetics data predicted that effective drug concentration could be achieved in vivo as a new medical treatment of meningioma., Conclusion: Meningioma cell growth is critically dependent on autocrine miR-483/IGF-2 stimulation and the IGF-2 pathway provides a feasible meningioma treatment target., (© 2023. The Author(s).)

miR-483-5p has been shown to play a key regulatory role in mediating a variety of biological activities. However, there are only a few studies on how miR-483-5p regulates osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), hence there is a need to explore the role and mechanism of miR-483-5p in regulating the osteogenic differentiation of hBMSCs. To that end, we used bioinformatics and cell experiments to confirm our hypothesis, a miRNA microarray dataset (GSE74209) and a mRNA dataset (GSE56816) were obtained from the GEO database, and the differentially expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were screened. In total, We found that the up-regulated candidate target genes were significantly enriched in the MAPK signaling pathway. Using the MCODE plug-in from Cytoscape, we identified RPL31 as the seed gene in the third major module. And we successfully established a possible miRNA-hub gene regulatory network. More importantly, we confirmed that the expression of miR-483-5p was down-regulated while the expression of RPL31 was up-regulated during osteogenic induction. Overexpression of miR-483-5p significantly inhibited osteogenic differentiation. In addition, western blot was used to measure protein levels of RPL31 and phosphorylated MEK/ERK family members. We demonstrated that miR-483-5p inhibits the RAS/MEK/ERK signaling pathway by targeting RPL31 and inhibiting its expression, thereby playing an inhibitory role in osteogenic differentiation. In light of our findings, RPL31 can be used as a novel therapeutic target for bone defects and osteoporosis, we reveal a newly discovered mechanism of osteogenic differentiation and provide a new strategy for treating osteoporosis and related diseases., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) is a life-impairing disorder, and early successful treatment is important for a favorable prognosis. However, early response to antidepressants differs widely among individuals, and is difficult to predict pre-treatment. As miRNAs have been reported to play important roles in depression, identification of miRNAs associated with antidepressant treatment responses and their interacting genes and pathways will be beneficial in understanding the predictors and molecular mechanisms of depression treatment. This randomized control trial examined miRNAs correlated with the early therapeutic effect of selective serotonin reuptake inhibitors (SSRIs; paroxetine or sertraline) and mirtazapine monotherapy. Before medication, we comprehensively analyzed the miRNA expression of 92 depressed participants and identified genes and pathways interacting with miRNAs. A total of 228 miRNAs were significantly correlated with depressive symptoms improvements after 2 weeks of SSRIs treatment, with miR-483.5p showing the most robust correlation. These miRNAs are involved in 21 pathways, including TGF-β, glutamatergic synapse, long-term depression, and the mitogen-activated protein kinase (MAPK) signaling pathways. Using these miRNAs enabled us to predict SSRI response at week 2 with a 57% difference. This study shows that pre-treatment levels of miRNAs could be used to predict early responses to antidepressant administration, a knowledge of genes, and an identification of genes and pathways associated with the antidepressant response.

The stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro . We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gu, Wang, Wang, Li, Liu, Lin, Yang, Zhang and Liu.)

Background: MicroRNAs, as small non-coding RNAs, play an important role in tumorigenesis. MiR-483-5p was found to have a significant increase as a diagnostic biomarker of nasopharyngeal carcinoma (NPC), not only in plasma from NPC patients but also in tumor cell lines and biopsy tissues in our previous study. However, its function and mechanism in NPC are still unclear., Methods: Tissue microarray including 178 primary NPC and 35 adjacent non-cancerous nasopharyngeal mucosal tissues was used to further validate the overexpression of miR-483-5p. Wound healing and invasion assays were conducted to verify its biological function. RNA sequencing (RNA-seq) and dual-luciferase reporter assay was performed to explore its target, and it was verified in fresh biopsy tissues from 23 NPC patients and 9 patients with chronic nasopharyngitis., Results: MiR-483-5p was highly expressed in NPC tissues than in adjacent non-cancerous tissues. It was found to have a significant correlation with poor overall survival (OS) [hazard ratio (HR) = 2.89, 95% confidence interval (CI) = 1.00-8.35, p  = 0.041] and progression-free survival (PFS) (HR = 1.95, 95%CI = 1.06-3.60, p  = 0.029) of NPC patients. Silencing of its expression inhibited the migratory and invasive capacities of NPC cells in vitro . EGR3 (early growth response 3) was identified as a direct target, and inhibiting miR-483-5p expression markedly enhanced the expression of EGR3 at both the mRNA and protein levels. Besides, a significant decrease of EGR3 expression was found in fresh biopsy tissues from NPC patients, in contrast to miR-483-5p expression. Furthermore, directly decreasing the expression of EGR3 could enhance the migration and invasion of NPC cells., Conclusion: The newly identified miR-483-5p/ EGR3 pathway provides further insights into the development and metastasis of NPC and may provide a potential therapeutic target for NPC treatment in order to improve survival of NPC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Tu, Zhou, Zhang, Xiao, Yang, Zhang, You and Zheng.)

Objective: To investigate the role of FKBP4 protein in cisplatin-induced premature ovarian insufficiency (POI)., Objective: We performed ITRAQ assay of the ovarian tissues from 4 mice with cisplatin-induced POI and 4 control mice, and identified FKBP4 as a significantly down-regulated protein in the oocytes and granulosa cells following cisplatin treatment. TargetScan software was used for target analysis of FKBP4, and qRT-PCR and Western blotting were used to verify the expression levels of miR-483-5p and FKBP4 in the mouse models. Serum samples were collected from patients with POI and healthy women for detecting miR-483-5p level with qRT-PCR. Cell transfection and dual-luciferase assay were performed to determine the relationship between miR-483-5p and FKBP4. In primary granulosa cells and KGN cells, we examined the effect of miR-483-5p alone, miR-483-5p and cisplatin, and miR-483-5p combined with both cisplatin and FKBP4 on cell apoptosis. We also assessed ovarian function in a transgenic mouse model with ovarian miR-483-5p overexpression in comparison wigh wildtype mice using immunofluorescence assay, in situ hybridization and ELISA., Objective: Ovarian FKBP4 expression was significantly decreased in mice with cisplatin-induced POI. Analysis using TargetScan software indicated that FKBP4 was the potential target of miR-483-5p, which was highly expressed in the ovaries and serum of POI mice and in the serum of patients with POI. In vitro experiments further confirmed that FKBP4 was the target of miR-483-5p. In KGN and primary granulosa cells, FKBP4 overexpression significantly reduced cell apoptosis induced by both cisplatin and miR-483-5p overexpression ( P = 0.0045 and 0.0177, respectively). In the transgenic mice with miR-483-5p overexpression in the oocytes, cisplatin induced more severe ovarian damages as compared with those in the wild-type mice., Objective: miR-483-5p/FKBP4 is a new and important pathway in cisplatin-induced POI, in which cisplatin increases ovarian miR- 483-5p expression to result in targeted downregulation of FKBP4. Up-regulation of miR-483-5p may increase ovarian sensitivity to cisplatin and cause severe ovarian dysfunction. Detection of serum miR-483-5p level may help to predict the occurrence and development of POI.

Background: Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case-control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis., Methods: We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound., Results: In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06-3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06-3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007)., Conclusion: miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.

Inflammation status are especially for tumor growth, and microRNAs (miRNAs) confirmed to participate in cancer occurrence and progression. However, the role of miR-483-5p and the relation with inflammation have not been elucidated in renal cell cancer (RCC). In this study, we intended to explore miR-483-5p expression and the relationship of inflammation status in clear cell renal cell cancer (ccRCC). Using microarray and qRT-PCR (Quantitative Real-time Polymerase Chain Reaction), we investigated the miR-483-5p expression in plasma and ccRCC cancer tissues. Then, we analyzed the correlation of miR-483-5p with clinicopathological parameters and inflammation status in ccRCC. Receiver operator characteristic (ROC) curves analysis was used to analyze the discrimination efficiency of miR-483-5p. in vitro experiments explored the biological role of miR-483-5p in renal cancer cells. miR-483-5p expression was upregulated in plasma of 5 patients with microarray and 12 patients with qRT-PCR in ccRCC at day 7 postoperatively. In addition, low expression of miR-483-5p was found in 58 ccRCC cancer tissues when compared with non-cancerous tissues. miR-483-5p could sufficiently discriminate ccRCC with the area under the curve (AUC) of 0.739 (P < .0001) from normal tissues. Higher expression of miR-483-5p was positively related to lower tumor stage and higher relative expression of miR-483-5p was inversely related to neutrophil-to-lymphocyte ratio (NLR) (P = .03) and lymphocyte-to-monocyte ratio (LMR) (P = .026). Overexpression of miR-483-5p lead to reverse epithelial-mesenchymal transition (EMT) process, restrain cell proliferation and metastasis of renal cancer cells. Our findings suggest that miR-483-5p expression is negatively correlation with inflammation status and may be a potential plasma biomarker for ccRCC., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Postmenopausal osteoporosis (PMOP) poses a significant threat to women's health worldwide. However, detailed molecular mechanism and therapeutic strategy for PMOP remain insufficient. Accumulating evidence suggests that miR-48-5p is implicated in the pathogenesis of osteoporosis. The present study aimed to determine the role and mechanism of miR-483-5p in PMOP. Results from PMOP patients demonstrated that miR-483-5p was up-regulated and SATB2 was down-regulated. Luciferase reporter assay identified SATB2 as a direct target gene of miR-483-5p. Experiments in MC3T3-E1 cells indicated that miR-483-5p mimic markedly inhibited cell viability as well as the expressions of OPG, RUNX2 and BMP2. And miR-483-5p inhibitor, SATB2-overexpressed lentiviruses (Lv-SATB2) or LY294002 (PI3K/AKT inhibitor) significantly reversed the above results. Similarly, PI3K/AKT signaling was activated by miR-483-5p mimic, and was inhibited in miR-483-5p inhibitor, Lv-SATB2 or LY294002 treated cells. In vivo experiments showed that miR-483-5p inhibitor significantly increased the bone mineral density and biomechanical parameters of femurs in ovariectomized (OVX) rats by targeting SATB2. In addition, the osteogenic differentiation and PI3K/AKT signaling were also regulated by miR-483-5p-SATB2 axis. Taken together, our findings indicated that miR-483-5p contributed to the pathogenesis of PMOP by inhibiting SATB2 and activating PI3K/AKT pathway. MiR-483-5p/SATB2 could be selected as a potential therapeutic target for PMOP.

Background: Ovarian cancer is the most deadly cancer that requires novel diagnostics and therapeutics. MicroRNAs are viewed as essential gene regulatory elements involved in different pathobiological mechanisms of many cancers, including ovarian cancer., Objective: This study examined the relationship between microRNA (miRNA) expression and response to platinum-based chemotherapy., Methods: Genome-wide miRNA expression analysis was conducted using Epithelial Ovarian Cancer (EOC) tissues from 25 patients with 17 malignant tumors and eight benign ovarian tumors. Candidate miRNAs that respond to platinum-based chemotherapy were selected for validation by quantitative RT-PCR., Results: Among 2,578 mature human miRNAs, high expression of miR-483-5p correlated with poor responses to platinum-based chemotherapy in EOC patients. Furthermore, high levels of miR-483-5p in the resistant group suppressed expression of the apoptotic regulator TAOK-1., Conclusion: A possible marker for the prediction of chemotherapy response and resistance in patients may be miR-483-5p. Choosing the right treatment for each patient with EOC can avoid the risk of developing chemotherapy resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: miR-483-5p has been reported to be an oncogene of various cancers, but its functional and regulatory mechanisms in esophageal cancer (EC) remain unclear. This study aimed to investigate the functional and molecular mechanisms of miR-483-5p in EC so as to provide a theoretical basis for exploring the therapeutic target for EC., Methods: miRNA expression profiles were downloaded from the TCGA-ESCA dataset to screen the target miRNA. Real-time quantitative PCR was performed to detect the transcriptional levels of miR-483-5p and KCNQ1 in EC cells. Western blot was conducted to determine the protein expression of KCNQ1. Cell Counting Kit-8 assay was carried out to assess cell proliferation. Transwell assay was performed to evaluate cell migration and invasion. Dual-luciferase reporter assay was conducted to verify the targeting relationship between miR-483-5p and KCNQ1., Results: miR-483-5p was up-regulated in EC cells and could bind to the 3'-untranslational region of KCNQ1. Over-expressing miR-483-5p suppressed KCNQ1 expression. Besides, miR-483-5p over-expression facilitated EC cell proliferation, migration and invasion, while its down-regulation triggered opposite result. Over-expressing miR-483-5p and KCNQ1 simultaneously could weaken the promoting effect of miR-483-5p over-expression on EC cell proliferation, migration and invasion., Conclusion: miR-483-5p as an oncogene facilitated EC cell proliferation, migration and invasion by targeted silencing KCNQ1, which is likely to provide a basis for further exploring the molecular mechanism of EC progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We have previously identified serum miR-483-5p as a preoperative diagnosis and prognosis biomarker for adrenocortical cancer (ACC). Here, we aimed to determine whether circulating miR-483-5p levels measured 3 months post-operatively distinguished patients with good prognosis (no recurrence for at least 3 years; NR3yrs) from patients with poor prognosis (recurrence or death within 3 years after surgery; R < 3yrs). We conducted a single-center retrospective analysis using sera from 48 patients with ACC that were initially non-metastatic and treated by surgery. Sera sampled within 3 months after surgery were available in 26 patients. MiR-483-5p absolute circulating levels were measured using quantitative PCR. Thirteen patients showed a recurrence before 3 years (=R < 3yrs). Thirteen patients showed no recurrence within 3 years, including 11 patients with a follow-up longer than 3 years (=NR3yrs). Serum miR-483-5p levels were higher in R < 3yrs than in NR3yrs: 1,541,990 ± 428,377 copies/mL vs. 388,457 ± 62,169 copies/mL ( p = 0.002). Receiver operating characteristic analysis showed that a value of 752,898 copies/mL distinguished R < 3yrs from NR3yrs with 61.5% sensitivity (CI 31.6-86.1) and 100% specificity (CI 71.5-100) with an area under the curve of 0.853. Patients with a value below this threshold had a significantly longer recurrence-free and overall survival. In multivariate analysis, miR-483-5p provided the single best prognostic value for recurrence-free survival (RFS) (hazard ratio (HR) for recurrence 5.98, p < 0.011) but not for overall survival. Our study suggests that serum miR-483-5p is a potent early post-operative biomarker for ACC prognosis that might be a better predictor of RFS than currently used markers.

Background: MiR-483-5p was recently identified as a risk factor in the early stages of acute myocardial infarction (AMI) patients. Here, we further investigated how miR-483-5p affects cardiomyocyte apoptosis and oxidative stress under hypoxic conditions., Methods: Plasma samples were collected from AMI patients and healthy volunteers. The expression of miR-483-5p was determined using quantitative real-time PCR. An in vitro hypoxic model was constructed to mimic AMI in AC16 cells. Cell viability, apoptosis and oxidative stress biomarker levels (MDA, SOD and CAT) were respectively determined using CCK-8, flow cytometry and commercial assay kits., Results: The expression levels of miR-483-5p were significantly higher in AMI patients than in control subjects. Circulating levels of miR-483-5p positively correlated with creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) levels. The in vitro experiments showed that the expression levels of miR-483-5p were also upregulated in hypoxia-induced AC16 cell injury. MiR-483-5p overexpression significantly increased hypoxia-induced cardiomyocyte apoptosis and oxidative stress, while knockdown attenuated these effects. Mechanistically, miR-483-5p directly targets MAPK3 in AC16 cells. Furthermore, the protective effects of miR-483-5p knockdown against hypoxia-induced cardiomyocyte injury are partially dependent on MAPK3., Conclusions: MiR-483-5p, which targets MAPK3, might be a potential therapeutic target for the diagnosis and prevention of hypoxia-induced myocardial injury., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Epithelial Ovarian Cancer (EOC) is often challenging to diagnose, even though histological examination. MicroRNA (miRNA or miRNA) is bound to the target messenger RNA (mRNA) due to which the mRNA molecules are silenced. The identification of miRNA expression- based EOC subtypes is considered a critical means of prognostication. So far, the studies on EOC subtypes have not been well characterized., Objective: This study aimed to confirm the existence of miRNAs in EOC and to assess their potential as clinical biomarkers for EOC., Methods: We sampled 25 ovarian tumor tissues from patients with human ovarian tumors (17 malignant; 12 serous EOC, five non-serous EOC, and eight benign ovarian tumors). miRNA microarray detection was performed to identify EOC miRNAs. Real-time PCR was adapted for the validation of differentially expressed miRNAs detected by microarray analysis related to hybridization intensity., Results: The results confirmed that miRNAs exist in EOC, relative expression of EOC miRNAs demonstrated that the upregulation of miR-483-5p, and downregulation of miR-127-3p, and miR- 532-5p were significantly expressed in the malignant group than in the benign group at p < 0.05. Besides, miR-483-5p could also distinguish EOC subtypes between serous EOC and non-serous EOC, with a p < 0.05., Conclusion: A comprehensive miRNA expression profiling can help to refine subtype classification in EOC, opening new opportunities for identifying clinically applicable markers for improved stratification and diagnostics of ovarian tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sepsis-induced acute lung injury (ALI) has high morbidity and mortality rates, and there remains a need for therapeutic methods to improve the outcome of ALI patients. miR-483-5p is an important regulator for the development of various diseases such as sepsis. Nevertheless, it is not known whether miR-483-5p has an effect on sepsis-induced ALI. To explore this issue, this study used cecal ligation and puncture (CLP)-treated mice and lipopolysaccharide (LPS)-treated pulmonary microvascular endothelial cells (PMVECs) cells to simulate the models of sepsis-induced ALI in vivo and in vitro. Pathological and histological changes of lungs from sepsis-induced ALI mice were detected by Hematoxylin-eosin staining. The detection levels of caspase-3, interleukin (IL)-6 and IL-1β were used to reflect the effect of miR-483-5p on apoptosis and inflammation of sepsis-induced ALI. The detection level of lactate dehydrogenase (LDH) in PMVECs cells was used to reflect the severe extent of sepsis-induced injury. The expression of miR-483-5p in lung tissues of sepsis-induced ALI mice was determined by qRT-PCR. In addition, the interaction of miR-483-5p with PIAS1 was identified and validated by Targetscan website and luciferase reporter assay, respectively. The results showed that miR-483-5p was up-regulated in the lung tissues of sepsis-induced ALI mice. Knockdown of miR-483-5p effectively ameliorated lung injury in mice with sepsis-induced ALI and inhibited inflammation and apoptosis of LPS-treated PMVECs cells. Furthermore, in vitro experiment revealed that PIAS1 was a potential target of miR-483-5p. Moreover, miR-483-5p could suppress PIAS1 expression to aggravate inflammation and apoptosis of LPS-treated PMVECs cells. These findings suggest miR-483-5p is a potential therapeutic and diagnostic biomarker for sepsis-induced ALI and provide a new insight for understanding the molecular mechanism of sepsis-induced ALI.

Introduction: Minimally invasive circulating microRNAs might be used for the preoperative differentiation of adrenocortical carcinoma (ACC) and adrenocortical adenoma (ACA). So far, the best blood-borne microRNA biomarker of ACC is circulating hsa-miR-483-5p. The expression of urinary hsa-miR-483-5p as a non-invasive marker of malignancy and its correlation with plasma hsa-miR-483-5p, has not been investigated, yet., Aim: Our aim was to investigate the expression of urinary hsa-miR-483-5p and its correlation with its plasma counterpart., Methods: Plasma and urinary samples from 23 ACC and 23 ACA patients were analysed using real-time RT-qPCR. To evaluate the diagnostic applicability of hsa-miR-483-5p, ROC-analysis was performed., Results: Significant overexpression of hsa-miR-483-5p was observed in carcinoma patients' plasma samples compared to adenoma patients' (p < 0.0001, sensitivity: 87%, specificity: 78.3%). In urinary samples, however, no significant difference could be detected between ACC and ACA patients., Conclusions: Plasma hsa-miR-483-5p has been confirmed as significantly overexpressed in adrenocortical cancer patients and thus might be exploited as a minimally invasive preoperative marker of malignancy. The applicability of urinary hsa-miR-483-5p for the diagnosis of adrenocortical malignancy could not be confirmed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus-induced and age-related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Meanwhile, we previously reported that miR-483-5p is essential for the initiation and development of OA by stimulating chondrocyte hypertrophy and angiogenesis. The connection between mTORC1 and miR-483-5p activation in OA progression, however, remains unclear. In this study, we elucidated their relationship and identified the underlying mechanisms. The expression of miR-483-5p in the articular cartilage of cartilage-specific TSC1 knockout mice was assessed compared with control mice using the Agilent Mouse miRNA (8*60K) V19.0 array and real-time polymerase chain reaction (RT-PCR). The functional effects of the stimulation of miR-483-5p via histone deacetylase 4 (HDAC4) by mTORC1 in OA development, subsequently modulating its downstream targets matrilin 3 and tissue inhibitor of metalloproteinase 2, were examined by immunostaining, western blotting, and real-time PCR. This study revealed that miR-483-5p was responsible for mTORC1 activation-stimulated OA. Mechanistically, mTORC1 controls the HDAC4-dependent expression of miR-483-5p to stimulate chondrocyte hypertrophy, extracellular matrix degradation, and subchondral bone angiogenesis, and it consequently initiates and accelerates the development of OA. Our findings revealed a novel mTORC1-HDAC4-miR-483-5p pathway that is critical for OA development., (© 2018 Wiley Periodicals, Inc.)

Adrenocortical carcinoma (ACC) is a tumor with poor prognosis in which overexpression of a panel of microRNAs has been associated with malignancy but a very limited number of investigations on their role in ACC pathogenesis have been conducted. We examined the involvement of miR-483-5p and miR-139-5p in adrenocortical cancer aggressiveness. Using bioinformatics predictions and mRNA/miRNA expression profiles, we performed an integrated analysis to identify inversely correlated miRNA-mRNA pairs in ACC. We identified N-myc downstream-regulated gene family members 2 and 4 (NDRG2 and NDRG4) as targets of miR-483-5p and miR-139-5p, respectively. NDRG2 and NDRG4 expressions were inversely correlated respectively with miR-483-5p and miR-139-5p levels in aggressive ACC samples from two independent cohorts of 20 and 44 ACC. Moreover, upregulation of miR-139-5p and downregulation of NDRG4 demonstrated a striking prognostic value. A direct interaction between miR-483-5p or miR-139-5p and their targets was demonstrated in reporter assays. Downregulation of miR-483-5p or miR-139-5p in the ACC cell lines NCI-H295R and SW13 increased NDRG2 or NDRG4 mRNA and protein expression, compromised adrenocortical cancer cell invasiveness and anchorage-independent growth. MiR-483-5p or miR-139-5p overexpression and NDRG2 or NDRG4 inhibition produce similar changes, which are rescued by NDRG2 or NDRG4 ectopic expression. We established that key factors mediating epithelial-to-mesenchymal transition are downstream effectors of miR-483-5p/NDRG2 and miR-139-5p/NDRG4 pathways. Collectively, our data show for the first time that miR-483-5p/NDRG2 and miR-139-5p/NDRG4 axes promote ACC aggressiveness, with potential implications for prognosis and therapeutic interventions in adrenocortical malignancies., (© 2018 UICC.)

RBM5 has been reported to be a candidate tumor suppressor gene which plays an important role in the induction of apoptosis. In this study, we investigated the effect of miR-483-5p on apoptosis of lung cancer cells and the underlying mechanism. We found that the expression of miR-483-5p mRNA was significantly up-regulated in lung cancer compared with adjacent para-cancerous tissues by using real-time PCR. Silencing miR-483-5p promoted A549 cell apoptosis and enhanced caspase-3 activity by flow cytometry with annexin V-FITC/PI staining and caspase-3 activity report kit. Western blotting demonstrated that miR-483-5p mimicked down-regulated RBM5 protein expression and miR-483-5p inhibitor up-regulated RBM5 protein expression. With additional bioinformatics analysis, we confirmed that RBM5 is a target gene of miR-483-5p and is favored for treating NSCLC. The immunohistochemical pattern of RBM5 could be used to predictoutcome for NSCLC. In conclusion, our results support that RBM5 expression can be regulated by miR-483-5p which is a prognostic marker for NSCLC patients. miR-483-5p inhibitor plays a role in lung cancer through targeting RBM5 to induce apoptosis., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease., Methods: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus (SLE) (n = 33) and primary Sjögren's syndrome (pSS) (n = 23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells., Results: 30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes., Conclusions: Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In the present study, we found that miR-483-5p was significantly upregulated in RHCC tissues of short-term recurrence (≤ 2 years) by miRNA microarray screening, and can significantly promote migration and invasion of HCC cells in vitro and increase intrahepatic metastasis in nude mice in vivo . Furthermore, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM), which significantly suppressed migration and invasion of HCC cells, was a direct target of miR-483-5p, and the re-introduction of ALCAM expression could antagonize the promoting effects of miR-483-5p on the capacity of HCC cells for migration and invasion. In addition, expression level of ALCAM was negatively correlated with microvascular invasion and tumor size recognized as prognostic factors. The cases which were negative for ALCAM expression had shorter time to recurrence than positive cases, and univariate and multivariate survival analyses showed that ALCAM was an independent risk factor of HCC recurrence. qRT-PCR and Western blotting showed that the expression of EMT related genes (MMP-2, MMP-9, E-caherin and vimentin) significantly changed as a result of interfering or overexpression of ALCAM, and ALCAM was significantly associated with EMT in HCC. These results suggest that the miR-483-5p/ALCAM axis is an important regulator in invasion and metastasis and biomarker for recurrence risk assessment of HCC.

Recent studies have suggested the critical roles of miRNAs for disease progression. miRNA-483-5p (miR-483-5p) was previously found to have a relationship with tumor cell behavior, but its biological function in Hirschsprung's disease (HSCR) remains undefined. Thus, we explored the role of miR-483-5p in the pathogenesis of HSCR. Histological changes of colonic tissues were evaluated by hematoxylin and eosin (HE) staining. Quantitative real-time PCR and western blotting were used to determine relative expression levels of miRNA, mRNA, and proteins in 20 HSCR patients and 20 normal colon tissues. In this study, we found that miR-483-5p expression in HSCR tissues was significantly increased and their downregulation promoted cell proliferation, cell cycle progression and invasion and inhibited cell apoptosis in human 293T and SH-SY5Y cell lines by the CCK-8, flow cytometry, and Transwell assay. GNDF family receptor alpha 4 (GFRA4) was confirmed as a downstream target of miR-483-5p by dual-luciferase reporter gene assay and inversely correlated with miR-483-5p expression in cell lines. Taken together, miR-483-5p may play a crucial role in the pathogenesis of HSCR by targeting GFRA4.

MicroRNAs (miRNAs) are small non-coding RNAs that promote the progression of cancer by negatively regulating gene expression. Down-regulation of miR-483-5p was reported in a number of cancers. However, the biological functions of miR-483-5p in esophageal squamous cell carcinomas are not fully understood. In this study, the expression levels of miRNAs in the immortalized human esophageal epithelial cell line SHEE and the malignantly transformed esophageal carcinoma cell line SHEEC were examined by miRNA microarray chip. The expression level of miR-483-5p was verified by a quantitative reverse transcription-polymerase chain reaction. Growth, apoptosis, and colony formation ability were also examined in SHEEC cells after transfection with inhibitors targeting miR-483-5p. And the target genes of miR-483-5p were predicted using bioinformatics approaches and the expression profile of SHEEC cells transfected with the miRNA inhibitors. protein levels of the target gene in SHEEC cells with a control or miRNA inhibitors were measured using Western blotting. The expression of miR-483-5p was elevated in SHEEC cells as compared to the SHEE cells. Silencing of miR-483-5p expression in SHEEC cells inhibited both the proliferation and formation of colonies and increased apoptosis. We also identified hepatocyte nuclear factor 4α (HNF4A) as a target of miR-483-5p in SHEEC cells. Knockdown of HNF4A recapitulated the effects of miR-483-5p. Our data showed that the miR-483-5p/HNF4A axis affected the malignant transformation of immortalized human esophageal epithelial cells and is a potential therapeutic target for ESCC., Competing Interests: None., (IJCEP Copyright © 2017.)

Healthy feto-maternal communication is critical during pregnancy and is orchestrated by the placenta. Dysfunction of the placenta leads to fetal growth complications; however, the underlying biological mechanisms have yet to be fully elucidated. Circulating extracellular microRNAs (exmiRNAs) in the blood have been implicated in cell-to-cell communication. Therefore, exmiRNAs may provide useful biological information about communication between the mother, the fetus, and the placenta during pregnancy. We used logistic regression to determine the association of exmiRNAs with abnormal fetal growth by comparing mothers of infants classified as small-for-gestational age (SGA) (n = 36) and large-for-gestational age (LGA) (n = 13) to appropriate-for-gestational age (AGA), matched by gestational age at delivery and infant sex. In addition, we used linear regression to determine associations between exmiRNAs and birth weight-for-gestational age (BWGA) z-score (n = 100), adjusting for maternal age, body mass index, and parity. We found that higher levels of miR-20b-5p, miR-942-5p, miR-324-3p, miR-223-5p, and miR-127-3p in maternal serum were associated with lower odds for having a SGA vs. AGA infant, and higher levels of miR-661, miR-212-3p, and miR-197-3p were associated with higher odds for having a LGA vs. AGA infant. We also found associations between miR-483-5p, miR-10a-5p, miR-204-5p, miR-202-3p, miR-345-5p, miR-885-5p, miR-127-3p, miR-148b-3p, miR-324-3p, miR-1290, miR-597-5p, miR-139-5p, miR-215-5p, and miR-99b-5p and BWGA z-score. We also found sex-specific associations with exmiRNAs and fetal growth. Our findings suggest that exmiRNAs circulating in maternal blood at second trimester are associated with fetal growth. Validation of our findings may lead to the development of minimally-invasive biomarkers of fetal growth during pregnancy.

Transforming growth factor-β1 (TGF-β1) has been reported to improve chondrocytes phenotype and function. The expression levels of microRNA-483-5p (miR-483-5p), a potential regulator of TGF-β signaling pathway, were elevated in chondrocytes of patients with osteoarthritis. In this study, we aimed to explore the role of miR-483-5p for the expression of cartilage-related genes in chondrocytes. Human chondrocytes were harvested from femoral condyle and tibial plateau of different donors (n = 10) following amputation due to sarcomas not involving the joint space. The expression levels of miR-483-5p and TGF-β1 mRNA were measured by qRT-PCR. Runt-related transcription factor 2 (RUNX2) is a transcription factor involved in chondrocyte differentiation, and type II collagen-degrading matrix metalloproteinase13 (MMP13) contributes to cartilage degradation. qRT-PCR was also used to measure the levels of RUNX2 and MMP-13 mRNAs, as well as type II collagen alpha 1 (COL2A1) and aggrecan mRNAs. COL2A1 and aggrecan are major cartilage extracellular matrix proteins that are essential for normal cartilage function. The expression levels of miR-483-5p were significantly increased in chondrocytes from Passage 0 to 2, whereas the expression levels of TGF-β1 mRNA were marginally decreased. Passage 1 chondrocytes were employed for following experiments. MiR-483-5p overexpression reduced TGF-β1 expression, while miR-483-5p knockdown dramatically elevated TGF-β1 expression both at mRNA and protein levels. Further, miR-483-5p overexpression significantly decreased the levels of COL2A1 and aggrecan mRNAs, and increased those of RUNX2 and MMP13 mRNAs, by down-regulating TGF-β1 expression. These findings suggest that modulating miR-483-5p expression may contribute to maintaining the cartilage tissues.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cause of cancer-associated mortality. Uncovering novel molecular biomarkers that can predict ESCC development will improve personalized therapy., Objective: The goal of the current study was to investigate the expression pattern of miR-483-5p and determine its prognostic value in ESCC., Methods: We first analyzed miRNA-seq data obtained from the Cancer Genome Atlas (TCGA) cohort to evaluate the prognostic value of miR-483-5p in ESCC. Then quantitative real-time RT-PCR (qRT-PCR) was carried out to compare the miR-483-5p levels in 80 pairs of ESCC tissues and adjacent non-cancerous tissues. The correlation between miR-483-5p levels and clinical features were determined., Results: For the TCGA cohort, ESCC patients with higher miR-483-5p had significantly shorter overall survival time. The examined ESCC cancer tissues exhibited a remarkable increment in miR-483-5p expression compared with the adjacent normal tissues. miR-483-5p was positively correlated with TNM stage, lymph nodes metastasis and T stage. In addition, upregulate miR-483-5p expression was also found to be significantly associated with poor survival of ESCC patients. Furthermore, miR-483-5p expression was an independent prognostic factor for overall survival and disease free survival in ESCC patients., Conclusions: Our study demonstrates that miR-483-5p might be a tumor promoter of ESCC, which provide a promising prognostic biomarker and therapeutic target.

Deregulation of microRNAs (miRNAs) is essential to tumor development, and serum miRNA profiles have been reported in several cancers. However, the serum miRNA profile in oral squamous cell carcinoma (OSCC) remained unclear. The present study aimed to explore abnormal miRNA profile in sera samples from OSCC patients and the association of miR-483-5p with patient prognosis. Microarray analysis was performed in sera from OSCC patients versus healthy controls. miR-483-5p expression was measured by reverse transcription (RT)-PCR and correlated to clinicopathological characteristics of OSCC patients. The prognostic significance was then evaluated with a Kaplan-Meier curve and log-rank tests, using a Cox proportional hazard model. According to microRNA array, 16 miRNAs were upregulated and 10 were downregulated in OSCC patient sera. miR-483-5p expression was significantly increased in OSCC patients (3.23-fold, p < 0.01), and this was significantly correlated with tumor nodal metastasis (TNM) stage and lymph nodal metastases (p < 0.01, p < 0.01). For predicting OSCC, receiver operating characteristic (ROC)/area under the curve (AUC) analysis confirmed a AUC of 0.85 (sensitivity of 0.853 and specificity of 0.746). OSCC patients with high serum miR-483-5p had lower survival than those with low expression, and multivariate analyses for overall survival revealed that high serum miR-483-5p expression was an independent prognostic factor for OSCC (HR = 2.32, 95 %CI 1.20-4.48). miR-483-5p expression increased in OSCC patient sera, and this may be a novel diagnostic and prognostic biomarker for OSCC.

Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: The purpose of this study was to identify the microRNAs that regulate the response of chondrocytes to loss of matrix interaction., Materials and Methods: MicroRNA and gene expression was compared in bovine cartilage and isolated chondrocytes using array analysis. Those microRNAs showing more than three-fold change in expression were verified by quantitative PCR after a stem-loop reverse transcription in bovine and human cartilage, and chondrocytes. Their function was investigated using target gene reporter construct expression, quantification of cell proliferation, and analysis of gene expression and matrix synthesis after transfection with microRNA mimics., Results: Only four microRNAs were confirmed to have a greater than three-fold change in expression after isolation of bovine or human chondrocytes from their extracellular matrix; miRs-221, -222 and -21 showed increased expression and miR-483-5p showed decreased expression. Transfection with a miR-221 mimic was shown to suppress expression of the cyclin-dependent kinase inhibitor p27 leading to the stimulation of chondrocyte proliferation. Transfection of chondrocytes with a miR-483-5p mimic was shown to suppress several members of the mitogen activated protein kinase (MAPK) pathway; a likely explanation of the increased matrix production observed., Conclusions: microRNAs 221 and 483-5p respond to the loss of chondrocyte matrix interaction by respectively stimulating proliferation by suppression of inhibitors of cell division and suppression of matrix production possibly by release of inhibition of the MAPK pathway.

Background and Goals: There are no highly sensitive and specific minimally invasive biomarkers for hepatocellular carcinoma (HCC) to date. The objective of this study was to identify serum microRNAs (miRNAs) as potential HCC biomarkers., Methods: Using miRCURY LNA™ microRNA arrays, the levels of circulating miRNAs in the serum of patients with HCC were compared and controls were matched. Then 253 subjects (112 HCC, 85 chronic hepatitis B [CHB], and 56 healthy controls) were recruited and 12 serum miRNAs were compared by quantitative real-time polymerase chain reaction (qRT-PCR). It was followed by the comparison of serum miRNA concentrations before and after the surgical resection in HCC group., Results: Median levels of miR-483-5p and miR-500a were higher in HCC patients than in patients with CHB and in healthy controls (p < 0.0001), but there were no differences between CHB patients and healthy controls (p > 0.05) and miR-483-5p levels were significantly reduced in serum samples obtained 30 days after surgical resection (p < 0.0001). The area under receiver operating characteristic curves of miR-483-5p and miR-500a was 74% (cutoff [Ct] value = 2.824, sensitivity = 74%, and specificity = 66%) and 66% (Ct value = 1.830, sensitivity = 74%, and specificity = 51%) for the prediction of HCC, respectively. In detecting HCC, combining α-fetoprotein (AFP) and serum miR-483-5p (sensitivity = 81% and specificity = 83%) was better than AFP alone (sensitivity = 78%, specificity = 70%)., Conclusion: Our observations suggest that serum miR-483-5p and miR-500a might serve as novel, noninvasive biomarkers for HCC. Serum miR-483-5p might complement AFP in detecting HCC.