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Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-β (TGF-β), TGF-β receptor 2 (TGFBR2), β-catenin, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses.

Pterygium is a multifactorial disease in which UV-B is speculated to play a key role by inducing oxidative stress and phototoxic DNA damage. In search for candidate molecules that are useful for justifying the intense epithelial proliferation observed in pterygium, our attention has been focused on Insulin-like Growth Factor 2 (IGF-2), mainly detected in embryonic and fetal somatic tissues, which regulate metabolic and mitogenic functions. The binding between IGF-2 and its receptor Insulin-like Growth Factor 1 Receptor (IGF-1R) activates the PI3K-AKT pathway, which leads to the regulation of cell growth, differentiation, and the expression of specific genes. Since IGF2 is regulated by parental imprinting, in different human tumors, the IGF2 Loss of Imprinting (LOI) results in IGF-2- and IGF2-derived intronic miR-483 overexpression. Based on these activities, the purpose of this study was to investigate the overexpression of IGF-2, IGF-1R, and miR-483. Using an immunohistochemical approach, we demonstrated an intense colocalized epithelial overexpression of IGF-2 and IGF-1R in most pterygium samples (Fisher's exact test, p = 0.021). RT-qPCR gene expression analysis confirmed IGF2 upregulation and demonstrated miR-483 expression in pterygium compared to normal conjunctiva (253.2-fold and 12.47-fold, respectively). Therefore, IGF-2/IGF-1R co-expression could suggest their interplay through the two different paracrine/autocrine IGF-2 routes for signaling transfer, which would activate the PI3K/AKT signaling pathway. In this scenario, miR-483 gene family transcription might synergically reinforce IGF-2 oncogenic function through its boosting pro-proliferative and antiapoptotic activity. [ABSTRACT FROM AUTHOR]

Objective: To exam the role of miR-92a/KLF2/miR-483 in the pathogenesis of metabolic syndrome., Methods: In this study, the serum of healthy controls and patients with metabolic syndrome were collected to detect the circulating level of miR-92a and miR-483. In vitro cultured HUVECs, overexpression or suppression of miR-92a, miR-483 or KLF2 to determine the relationship among miR-92a, KLF2 and miR-483. Ang II, ox-LDL, or high glucose treatment were used to mimic the metabolic syndrome. HUVECs or HepG2 cells were treated with Telmisartan, Atorvastatin, or metformin, the miR-483 and its target gene expression was detected. In animal experiment, ob/ob mice were chose to confirm the changes of miR-92a, KLF2, and miR-483., Results: Compared with the healthy controls, the level of miR-92a was significantly increased, while miR-483 level was remarkably decreased in the patients with metabolic syndrome. In vitro cultured HUVECS, overexpression of miR-92a significantly reduced the expression of miR-483, but overexpression of miR-483 had no effect on miR-92a. Overexpression of KLF2 could downregulate miR-483 level, while inhibition of KLF2 had the opposite effect. When HUVECs and HepG2 were stimulated with Ang II, ox-LDL and high glucose, the expression of miR-483 was significantly decreased and its target genes was increased. Anti-miR-92a could reverse the effect. Furthermore, Telmisartan, Atorvastatin, and Metformin significantly increased miR-483 expression and decreased its target gene expression, which could be reversed by miR-92a mimic. The level of miR-92a was significantly increased in HepG2 cells, which were treated with exosomes derived from endothelial cells with miR-92a overexpression. ob/ob mice showed the similar effects., Conclusions: Endothelial dysfunction and fatty liver are critically involved in the pathogenesis of metabolic syndrome. MicroRNAs can mediate the cellular communication between vascular endothelial cells (ECs) and distal cell. Serum miR-92a level was higher in metabolic syndrome patients than controls. KLF2 is the target gene of miR-92a, which can increase the production of miR-483, miR-483 acts on its target genes CTGF, ET-1, and β-catenin to protect cell function. EC miR-92a is secreted out of cells into the blood, circulates through the blood to the liver, and continues to exert its biological effects after being absorbed by hepatocytes. LNA-miR-92a administration reversed endothelial cell damage and fatty liver caused by metabolic syndrome by affecting the KLF2/miR-483 pathway., (© 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

RationaleEndothelial-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD.ObjectiveWe investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied.Methods and resultsSera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells. Cardiovascular disease-related miRNAs, CTGF, and EndoMT markers were quantified using reverse transcriptase quantitative polymerase chain reaction, ELISA, and Western blotting. Compared with healthy controls, human umbilical vein endothelial cell incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3' untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in endothelial cells in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in endothelial cells.ConclusionsKD sera suppress the KLF4-miR-483 axis in endothelial cells, leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part, through the restoration of KLF4-miR-483 expression.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01431105.

Abstract Background Osteosarcoma is one of the most prevalent primary bone tumours in adolescents. Accumulating evidence shows that aberrant expression of the long non-coding RNA (lncRNA) NEAT1 and microRNA-483 (miR-483) contribute to the epithelial-mesenchymal transition (EMT), invasion and metastasis of tumour cells. However, the potential regulatory effects of NEAT1 and miR-483 on the EMT of osteosarcoma remain elusive. Methods The expression of the NEAT1, miR-483, signal transducer and activator of transcription-1 (STAT1), STAT3, and EMT-associated markers was measured using qRT-PCR or western blotting. NEAT1 overexpression or knockdown was induced by lentivirus-mediated transfection. A luciferase reporter assay was employed to confirm the association between NEAT1/miR-483 and miR-483/STAT3. RNA immunoprecipitation (RIP) was also performed to verify the NEAT1 and miR-483 interaction. Wound healing and transwell assays were implemented to assess the migration and invasion of U2OS cells. Unilateral subcutaneous injection of U2OS into nude mice was performed to investigate tumour metastasis in vivo. Results The expression of miR-483 was downregulated in both osteosarcoma cell lines and osteosarcoma tissues. The overexpression of miR-483 suppressed the migration, invasion, and expression of EMT-associated proteins in U2OS cells, while simultaneous overexpression of STAT3 partially relieved this suppression. Mechanistically, miR-483 specifically targeted the 3′ untranslated region (3′UTR) of STAT3 and repressed its expression. However, NEAT1 sponged miR-438, increased STAT3 expression, and repressed STAT1 expression, subsequently increasing the EMT of osteosarcoma cells. The knockdown of NEAT1 in transplanted U2OS cells impaired the liver and lung metastases of osteosarcoma in nude mice. Moreover, NEAT1 silencing inhibited the mesenchymal- epithelial transition (MET) of osteosarcoma at metastasis sites. Conclusions The lncRNA NEAT1/miR-483/STAT3 axis plays a crucial role in regulating the metastasis of osteosarcoma and potentially represents one appealing therapeutic target for osteosarcoma treatment in the future.

Abstract Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR‐483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA‐seq and bioinformatics analyses showed that miR‐483 targets several PAH‐related genes, including transforming growth factor‐β (TGF‐β), TGF‐β receptor 2 (TGFBR2), β‐catenin, connective tissue growth factor (CTGF), interleukin‐1β (IL‐1β), and endothelin‐1 (ET‐1). Overexpression of miR‐483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF‐β, TGFBR2, β‐catenin, CTGF, IL‐1β, and ET‐1. In contrast, inhibition of miR‐483 increased these genes in ECs. Rats with EC‐specific miR‐483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR‐483. These results indicate that PAH is associated with a reduced level of miR‐483 and that miR‐483 might reduce experimental PH by inhibition of multiple adverse responses.

Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2 / H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling. [Display omitted] • In the mouse, expression of imprinted Mir483 is dependent on Igf2 transcription • Mir483 is a developmental growth suppressor and Igf1 is a major target gene • Transgenic Mir483 overexpression in utero leads to fetal demise • Post-natal Mir483 overexpression induces growth restriction and excessive adiposity Sandovici et al., using loss- and gain-of-function mouse models, dissect the mechanisms that regulate Mir483 expression and characterize its role in developmental growth and metabolism. They uncover that Mir483 actions repress IGF signaling, in particular Igf1 , and function in a manner opposite the growth-promoting host gene Igf2. [ABSTRACT FROM AUTHOR]

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Pancreatic β-cell dysfunction is central to the development and progression of type 2 diabetes. Dysregulation of microRNAs (miRNAs) has been associated with pancreatic islet dysfunction in type 2 diabetes. Previous study has shown that miR-483 is expressed relatively higher in β-cells than in α-cells. To explore the physiological function of miR-483, we generated a β-cell-specific knockout mouse model of miR-483. Loss of miR-483 enhances high-fat diet–induced hyperglycemia and glucose intolerance by the attenuation of diet-induced insulin release. Intriguingly, mice with miR-483 deletion exhibited loss of β-cell features, as indicated by elevated expression of aldehyde dehydrogenase family 1, subfamily A3 (Aldh1a3), a marker of β-cell dedifferentiation. Moreover, Aldh1a3 was validated as a direct target of miR-483 and overexpression of miR-483 repressed Aldh1a3 expression. Genetic ablation of miR-483 also induced alterations in blood lipid profile. Collectively, these data suggest that miR-483 is critical in protecting β-cell function by repressing the β-cell disallowed gene Aldh1a3. The dysregulated miR-483 may impair insulin secretion and initiate β-cell dedifferentiation during the development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is one of the most prevalent primary bone tumours in adolescents. Accumulating evidence shows that aberrant expression of the long non-coding RNA (lncRNA) NEAT1 and microRNA-483 (miR-483) contribute to the epithelial-mesenchymal transition (EMT), invasion and metastasis of tumour cells. However, the potential regulatory effects of NEAT1 and miR-483 on the EMT of osteosarcoma remain elusive. Methods: The expression of the NEAT1, miR-483, signal transducer and activator of transcription-1 (STAT1), STAT3, and EMT-associated markers was measured using qRT-PCR or western blotting. NEAT1 overexpression or knockdown was induced by lentivirus-mediated transfection. A luciferase reporter assay was employed to confirm the association between NEAT1/miR-483 and miR-483/STAT3. RNA immunoprecipitation (RIP) was also performed to verify the NEAT1 and miR-483 interaction. Wound healing and transwell assays were implemented to assess the migration and invasion of U2OS cells. Unilateral subcutaneous injection of U2OS into nude mice was performed to investigate tumour metastasis in vivo. Results: The expression of miR-483 was downregulated in both osteosarcoma cell lines and osteosarcoma tissues. The overexpression of miR-483 suppressed the migration, invasion, and expression of EMT-associated proteins in U2OS cells, while simultaneous overexpression of STAT3 partially relieved this suppression. Mechanistically, miR-483 specifically targeted the 3′ untranslated region (3′UTR) of STAT3 and repressed its expression. However, NEAT1 sponged miR-438, increased STAT3 expression, and repressed STAT1 expression, subsequently increasing the EMT of osteosarcoma cells. The knockdown of NEAT1 in transplanted U2OS cells impaired the liver and lung metastases of osteosarcoma in nude mice. Moreover, NEAT1 silencing inhibited the mesenchymal- epithelial transition (MET) of osteosarcoma at metastasis sites. Conclusions: The lncRNA NEAT1/miR-483/STAT3 axis plays a crucial role in regulating the metastasis of osteosarcoma and potentially represents one appealing therapeutic target for osteosarcoma treatment in the future. [ABSTRACT FROM AUTHOR]

Aim: Pre‐eclampsia is a serious pregnancy‐specific disease with an incidence of 9.4%. MicroRNAs play a key role in regulating factors in pre‐eclampsia, but related research is still limited. This study aims to reveal the role and potential mechanisms of miR‐483 in pre‐eclampsia. Methods: miR‐483 was detected in venous blood, umbilical cord blood and placental tissue of pre‐eclampsia patients by Real‐time Quantitative polymerase chain reaction (qRT‐PCR). Insulin‐like growth factor (IGF1) and miR‐483 were detected by qRT‐PCR and western blot in endothelial progenitor cells isolated from fetal umbilical cord blood. miR‐483 was overexpressed and inhibited to detect changes of IGF1 and PI3K/Akt/mTOR pathway in endothelial progenitor cells by qRT‐PCR and western blot. Results: miR‐483 was downregulated in venous blood, umbilical cord blood and placental tissue of pre‐eclampsia patients. In endothelial progenitor cells, overexpression of miR‐483 inhibited the expression of IGF1, and inhibition of miR‐483 promoted the expression of IGF1. miR‐483 regulates the expression of PI3K, Akt, and mTOR in endothelial progenitor cells. Conclusion: miR‐483 is downregulated in pre‐eclampsia and regulates endothelial progenitor cells by targeting IGF1. miR‐483 is a potential alternative for diagnosing and treating pre‐eclampsia. [ABSTRACT FROM AUTHOR]

BACKGROUND: The role of microRNAs (miRs) as biomarkers to predict outcome in hepatoblastoma (HB), the most common malignant liver tumor in childhood, has still to be determined. Recently, the so-called four-miR signature has been described to efficiently stratify HB patients according to their prognosis. OBJECTIVE: We examined the recently described four-miR signature for its clinical relevance in an independent validation cohort of HB patients and tried to optimize its predictive value by analyzing four additional miRs involved in HB biology. METHODS: Expression of eight miR was determined in 29 tumor and 10 normal liver samples by TaqMan assays and association studies and Kaplan-Meier estimators determined their clinical relevance. RESULTS: Stratifying HB patients by the four-miR signature showed no difference in patients' outcome, which was also reflected by the lack of association with any clinical risk parameter. Adding miR-23b-5p and miR-23b-3p did also not increase its discriminating power. However, the integration of miR-483-5p and miR-483-3p into the four-miR signature could predict patients with poor outcome that were associated with large tumors and vessel invasive growth with high accuracy. CONCLUSIONS: The expansion of the four-miR signature by miR-483 serves as a useful biomarker to predict outcome of HB patients. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of Toddalia asiatica extract combined with miR-483 on osteoarthritis chondrocyte proliferation and apoptosis and expression of inflammatory factors. Osteoarthritis chondrocytes were treated with Toddalia asiatica extract. Osteoarthritis chondrocytes were transfected with anti-miR-483 or miR-483, and Toddalia asiatica extract was applied. The levels of TNF-α, IL-6, IL-10 were determined by ELISA. Cell proliferation and cloning were evaluated by MTT and cloning experiment. Cell apoptosis was determined by flow cytometry. P21 and caspase-3 protein expression were analyzed by Western blot. The expression of miR-483 was detected by qRT-PCR. The application of Toddalia asiatica extract or inhibition of miR-483 significantly increased the cell survival rate, cloning count and IL-10 level of osteoarthritis chondrocytes, and significantly reduced the apoptosis rate, levels of P21, Caspase-3, TNF-α IL-6 and miR-483 expression level of osteoarthritis chondrocytes (p<0.05). Overexpression of miR-483 could reverse the promotion effect of Toddalia asiatica extract on osteoarthritis chondrocytes proliferation, clone formation and IL-10 level, as well as reserve the inhibition effect of Toddalia asiatica extract on osteoarthritis chondrocyte apoptosis and levels of P21, caspase-3, TNF-α, IL-6. The combination of Toddalia asiatica extract and miR-483 can promote the proliferation of osteoarthritis chondrocytes and inhibit apoptosis and expression of inflammatory factors. [ABSTRACT FROM AUTHOR]

aim of this study was to investigate the potential therapeutic targets for gliomas. Materials and Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to calculate the expression of miRNA and genes. The connection between the expression of miR-483 and patients' overall survival rate was evaluated using Kaplan–Meier analysis. In addition, the underlying mechanism was detected using luciferase assay. Results: The expression level of miR-483 was significantly decreased in glioma tissue samples and cell lines, compared to the adjacent tissues and normal cell lines. Downregulation of miR-483 or upregulation of SOX3 was associated with overall survival of glioma patients. Additionally, overexpression of miR-483 promotes cell invasion and migration and inhibits apoptosis. In addition, miR-483 directly targeted to SOX3, and the expression of miR-483 has a negative correlation with SOX3 in glioma tissues. SOX3 reversed partial functions of miR-483 on cell migration, invasion, and promoted cell apoptosis in glioma. Conclusion: MiR-483 inhibited glioma cell migration, invasion, and promoted glioma cell apoptosis by targeting SOX3. MiR-483 maybe acted as a potential target for the treatment of glioma. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been established to regulate skeletal muscle development in mammals. However, few studies have been conducted on the regulation of proliferation and differentiation of bovine myoblast cells by miRNAs. The aim of our study was to explore the function of miR‐483 in cell proliferation and differentiation of bovine myoblast. Here, we found that miR‐483 declined in both proliferation and differentiation stages of bovine myoblast cells. During the proliferation phase, the overexpression of miR‐483 downregulated the cell cycle–associated genes cyclin‐dependent kinase 2 (CDK2), proliferating cell nuclear antigen (PCNA) messenger RNA (mRNA), and the protein levels. At the cellular level, cell cycle, cell counting kit‐8, and 5‐ethynyl‐2´‐deoxyuridine results indicated that the overexpression of miR‐483 block cell proliferation. During differentiation, the overexpression of miR‐483 led to a decrease in the levels of the myogenic marker genes MyoD1 and MyoG mRNA and protein. Furthermore, the immunofluorescence analysis results showed that the number of MyHC‐positive myotubes was reduced. In contrast, the opposite experimental results were obtained concerning both proliferation and differentiation after the inhibition of miR‐483. Mechanistically, we demonstrated that miR‐483 target insulin‐like growth factor 1 (IGF1) and downregulated the expression of key proteins in the PI3K/AKT signaling pathway. Altogether, our findings indicate that miR‐483 acts as a negative regulator of bovine myoblast cell proliferation and differentiation. MicroRNA‐483 (miR‐483) inhibits bovine myoblast cell proliferation and differentiation by targeting insulin‐like growth factor 1 (IGF1) and downregulated the expression of key proteins in the PI3K/AKT signaling pathway. These results will provide an insight target in breeding strategies appealing to cattle industry. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the expression of miR-483 and miR-483* and the relationship among them, their host gene (Igf2), and other cytokines in a murine model of renal fibrosis. The extent of renal fibrosis was visualized using Masson staining, and fibrosis was scored 3 days and 1 and 2 weeks after unilateral ureteral obstruction (UUO). Expression of miR-483, miR-483* and various cytokine mRNAs was detected by real-time polymerase chain reaction (PCR). Expression of miR-483 and miR-483* was significantly upregulated in the UUO model, particularly miR-483 expression was the greatest 2 weeks after surgery. Additionally, miR-483 and miR-483* expression negatively correlated with Bmp7 expression and positively correlated with Igf2, Tgfβ, Hgf, and Ctgf expression, as determined by Pearson's correlation analysis. Hgf expression significantly increased at 1 and 2 weeks after the surgery compared to the control group. This study showed that miR-483 and miR-483* expression was upregulated in a murine UUO model. These data suggest that miR-483 and miR-483* play a role in renal fibrosis and that miR-483* may interact with miR-483 in renal fibrosis. Thus, these miRNAs may play a role in the pathogenesis of renal fibrosis and coexpression of their host gene Igf2.

OBJECTIVE: To explore the mechanism underlying the effect of microRNA-483 (miR-483) in the progression of breast cancer (BC). PATIENTS AND METHODS: MiR-483 expression was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in both BC cells and tissue samples. The associations between miR-483 expression level and patients' overall survival rate were explored. Furthermore, cell proliferation assay and cell apoptosis assay were conducted, respectively. In addition, Western blot analysis and Luciferase assay were performed to explore the underlying mechanism. RESULTS: The expression level of miR-483 was significantly decreased in tumor samples compared to that in adjacent tissues, which was also associated with patients' overall survival time. Moreover, cell growth was promoted, and cell apoptosis was inhibited after miR-483 was knocked down in vitro. Furthermore, SOX3 acted as a direct target of miR-483, and the expression of SOX3 was negatively correlated with the expression of miR-483 in tumor tissues. CONCLUSIONS: These results suggested that miR-483 could suppress BC cell proliferation and promote BC cell apoptosis via targeting SOX3, which might be a potential therapeutic target in BC. [ABSTRACT FROM AUTHOR]

ABSTRACT MicroRNAs (miRNAs) can regulate cellular differentiation processes by modulating multiple pathways simultaneously. Previous studies to analyze in vivo miRNA expression patterns in developing human limb cartilage tissue identified significant downregulation of miR-483 in hypertrophic chondrocytes relative to proliferating and differentiated chondrocytes. To test the function of miR-483 during chondrogenesis, lentiviral strategies were used to overexpress miR-483 during in vitro chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). While the in vivo expression patterns led us to hypothesize that miR-483 may enhance chondrogenesis or suppress hypertrophic marker expression, surprisingly, miR-483 overexpression reduced chondrocyte gene expression and cartilage matrix production. In addition, cell death was induced at later stages of the chondrogenesis assay. Mechanistic studies revealed that miR-483 overexpression resulted in downregulation of the TGF-β pathway member SMAD4, a known direct target of miR-483-3p. From these studies, we conclude that constitutive overexpression of miR-483 in hBM-MSCs inhibits chondrogenesis of these cells and does not represent an effective strategy to attempt to enhance chondrocyte differentiation and anabolism in this system in vitro. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2369-2377, 2017. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs that constitute a fundamental part of post-transcriptional gene regulation in mammalian cells. We have recently identified the intronic miR-483, which functions as an important regulator of protein synthesis during mild hypothermia in human and rodent cells. Since only very little is known about transcriptional regulation of intronic miRNAs and their host genes, we thoroughly investigated the regulation of miR-483 expression and its host gene IGF2 in HeLa cells. We demonstrate that miR-483 is regulated and expressed independently of its host gene IGF2 during mild hypothermia. Strikingly, we also discovered that miR-483 enhances its own transcription by up-regulation of the transcription factor USF1, which activates a promoter element upstream of the MIR483 gene. However, since the USF1 mRNA lacks binding sites for miR-483-5p and -3p, USF1 expression is likely enhanced in an indirect manner. Our results suggest that miR-483 may self-regulate its own expression independently of its host gene IGF2 in human HeLa cells. This points towards a novel feed-forward mechanism, in which selected intronic miRNAs may activate their own expression by transcriptional activation of upstream regulators. [ABSTRACT FROM AUTHOR]

ABSTRACT Cell engineering and bioprocess optimizations such as low temperature cultivation represent powerful tools to improve cellular performance and product yields of mammalian production cells. Besides monoclonal antibodies (mABs), novel biotherapeutic formats such as viral vectors will gain increasing importance. Here, we demonstrate that similar to Chinese hamster ovary (CHO) cells, product yields of recombinant adeno-associated virus (rAAV) producing HeLa cells can be markedly increased by low temperature cultivation. MicroRNAs (miRNAs) are small non-coding RNAs that critically regulate cell phenotypes. We thus investigated differential miRNA expression in response to mild hypothermia in CHO and HeLa production cells. We discovered miR-483 to be substantially up-regulated upon temperature down-shift in both cell types. Functional validation experiments revealed that introduction of miR-483 mimics led to a significant increase in both rAAV and mAB production in HeLa and CHO cells, respectively. Furthermore, inhibition of miR-483 up-regulation during mild hypothermia significantly decreased product yields, suggesting that miR-483 is a key regulator of cellular productivity in mammalian cells. In addition, miRNA target gene identification indicated that miR-483 might regulate genes directly involved in cellular survival and protein expression. Our results highlight that miR-483 is a valuable tool for product-independent engineering of mammalian production cells. Biotechnol. Bioeng. 2016;113: 830-841. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) have been shown to be important regulators in the pathogenesis of osteoarthritis (OA). The objective of this study was to determine the expression levels of miR-483, miR-483*, their host gene (Igf2) and other cytokines in a murine model of OA. The expression of miR-483 was significantly up-regulated in old mouse and in all of the operation groups, particularly the group assessed 1 week after surgery. The expression of miR-483* was significantly increased in the old mouse group and the group assessed 5 weeks after surgery. The expression of miR-483 was negatively correlated with the expression of (mRNA) Bmp7 and TgfB and positively correlated with Mmp13 by Pearson correlation analysis, while miR-483* was positively correlated with Il1B. Surprisingly, there was no correlation between the expression of either miR-483 or miR-483* and Igf2. This study shows that the expression of miR-483 and miR-483* is up-regulated in murine OA. These data suggest that miR-483 and miR-483* may play critical roles in early and later pathogenesis of OA, respectively, without the involvement of their host gene Igf2. [Copyright &y& Elsevier]

Most intronic micro-RNAs are coexpressed with their host genes, suggesting that they may play similar roles. The function of miR-483 remains unknown, although it is embedded in an intron of Igf2 gene, which is an activator of hepatocellular carcinoma proliferation. In the present study, we provide evidence that Igf2-derived miR-483 can induce proliferation in hepatocellular carcinoma cells. The miR-483 promotion of proliferation was analysed by soft agar colony formation assay and proliferation curve assay. The effect of miR-483 on Socs3 expression was examined by Western blot and a reporter assay. Our results revealed that Igf2-derived intronic miR-483 was identified by the application of 94G6, an inhibitor of Igf2 at the transcriptional level. All results from the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay, the proliferation curve assay and the soft agar colony formation assay showed that miR-483 promoted the proliferation of hepatocellular carcinoma cells. Finally, Socs3, a putative target predicted by bioinformatics, was regulated by miR-483 at mRNA and protein levels. Direct binding with the 3′ UTR was identified by a luciferase activity assay. Our findings demonstrate that Igf2-derived intronic miR-483, through downregulation of its target Socs3, regulates hepatoma cell proliferation and thus may serve as a potential target for hepatocellular carcinoma therapy. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) serve an important role in cell differentiation, proliferation and apoptosis by negatively regulating gene expression at the transcriptional or post-transcriptional level. EI24 autophagy associated transmembrane protein (EI24) is a tumor suppressor gene that serves an important role in the occurrence and development of digestive system tumors. However, little is known regarding the relationship between EI24 and the prognosis of patients with colorectal cancer (CRC). Our previous study confirmed EI24 as the target molecule of miR-483, using reporter gene detection. Thus, the aim of the present study was to elucidate the effect of the abnormal expression of miR-483 on the malignant phenotype of CRC through a series of cell function experiments and nude mice tumorigenicity experiments, and to determine the expression level of EI24, a downstream target gene of miR-483, in CRC and its relationship with patient prognosis. In CRC tissues and cells, the expression level of miR-483 was upregulated, while the expression level of EI24 was downregulated. Cell function tests such as MTT assay, cell cycle assay, colony formation assay, Migration and invasion assays and nude mice tumorigenicity experiments demonstrated that the overexpression of miR-483 promoted the proliferation, invasion and metastasis of CRC. Moreover, the reverse transcription-quantitative PCR results indicated that overexpression of miR-483 inhibited the expression level of EI24. The relationship between the clinical data and immunohistochemical results from 183 patients with CRC and survival was examined. It was found that the expression level of EI24 was positively associated with the prognosis of patients. As a cancer-promoting factor, miR-483 enhances the proliferation, migration and invasion of CRC cells by reducing the expression level of EI24. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third leading cancer-related fatal disease in the world, and its morbidity and mortality are increasing. In recent years, the researches of miRNAs have provided new ideas for the diagnosis and treatment of colorectal cancer. Although previous studies have confirmed the abnormal expression of miR-483 in different types of tumors, the expression level of miR-483 in colorectal cancer remains to be elucidated. The effect of up-regulated miR-483 on colorectal cancer cell function was detected by cell function test. In order to further clarify the effect of up-regulation of miR-483 on colorectal cancer cells, we carried out tumorigenesis experiments in nude mice. The results showed that after transplantation of colorectal cancer cells subcutaneously in nude mice, the tumors in the over-expression group of miR-483 were significantly larger than those in the control group. miR-483 is an important regulator of the occurrence and development of colorectal cancer. The results of this study are helpful to understand the development of colorectal cancer and to formulate diagnosis and treatment strategies for colorectal cancer., (Copyright © 2021 by the Association of Clinical Scientists, Inc.)

MicroRNAs are important regulators during human growth and development. Emerging evidence indicates that microRNAs play important roles in colorectal cancer. The aim of this study is to reveal the biological function and direct target gene of miR-483 in colorectal cancer. The biological function of miR-483 on the proliferation and migration of colon cancer cells was then examined by Edu assay and transwell assay, respectively. Our findings revealed that miR-483 mimic could significantly inhibit cell proliferation and migration. The target gene of miR-483 was predicted by target scan software and identified by a dual fluorescence reporter system which showed that TRAF1 was a direct target gene of miR-483 in SW480 cell line. These data suggest that miR-483 is a colorectal cancer suppressor which could inhibit cell proliferation and migration, possibly via targeting TRAF1. The miR-483 could be a potential treatment target for colorectal cancer., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Digestive tract cancers (DTCs) is the most common malignant tumors in the world. Despite surgery and medical technology have witnessed the increasing development and sharp advancement in the past decade, DTCs remain a critical concern with high morbidity and mortality. Since a class of small noncoding RNAs termed miRNAs were identified several years ago, increasing studies have attempted to illustrate the relationship between the specific miRNAs dysregulated expression levels and the diseases phenotypic changes. For example, microRNA-483 (miR-483) aberrant expression plays a pivotal part in tumor biology in a variety of human cancer, including DTCs. In this review, we focus on the present key findings from recent profiling studies, discuss the use of miR-483 as a novel biomarker for DTCs. At the same time, we emphasize the significant diversities and technical difficulties must be overcome before clinically relevant signatures arose. It is believed that this might provide researchers an insight into the molecular targeting cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Insulin secreted from pancreatic β-cells and glucagon secreted from pancreatic α-cells are the two major hormones working in the pancreas in an opposing manner to regulate and maintain a normal glucose homeostasis. How microRNAs (miRNAs), a population of non-coding RNAs so far demonstrated to be differentially expressed in various types of cells, regulate gene expression in pancreatic β-cells and its closely associated α-cells is not completely clear. In this study, miRNA profiling was performed and compared between pancreatic β-cells and their partner α-cells. One novel miRNA, miR-483, was identified for its highly differential expression in pancreatic β-cells when compared to its expression in α-cells. Overexpression of miR-483 in β-cells increased insulin transcription and secretion by targeting SOCS3, a member of suppressor of cytokine signaling family. In contrast, overexpression of miR-483 decreased glucagon transcription and secretion in α-cells. Moreover, overexpressed miR-483 protected against proinflammatory cytokine-induced apoptosis in β-cells. This correlates with a higher expression level of miR-483 and the expanded β-cell mass observed in the islets of prediabetic db/db mice. Together, our data suggest that miR-483 has opposite effects in α- and β-cells by targeting SOCS3, and the imbalance of miR-483 and its targets may play a crucial role in diabetes pathogenesis., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)