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Asthma is viewed as an airway disease and an inflammatory condition. This study aims to reveal the role of Kruppel-like factor 5 (KLF5)-mediated pyroptosis of airway epithelial cells in airway inflammation in asthma. The asthmatic mouse model was established. The mice were infected with the lentivirus containing sh-KLF5, antagomiR-182–5p, and pc-Toll-like receptor 4 (TLR4). Airway hyperresponsiveness was measured, and the cells in bronchoalveolar lavage fluid (BALF) were sorted and counted. The expression levels of interleukin (IL)-4/IL-13/IL-6/IL-18/IL-1β/NOD-like receptor family pyrin domain containing 3 (NLRP3)/N-gasdermin D (GSDMD-N)/cleaved caspase-1 were detected. The pathological changes in lung tissue were observed. The enrichment of KLF5 in the miR-182–5p promoter region was measured. The binding relationship among KLF5, miR-182–5p, and TLR4 were analyzed. KLF5 was highly expressed in asthmatic mice. Silencing KLF5 improved airway resistance and lung dynamic compliance, reduced the cells in BALF and the expression of IL-4/IL-13/IL-6/NLRP3/GSDMD-N/cleaved caspase-1/IL-18/IL-1β, and alleviated the pathological changes. Mechanistically, KLF5 bonded to the miR-182–5p promoter to inhibit miR-182–5p expression, and miR-182–5p inhibited TLR4. Silencing miR-182–5p or TLR4 overexpression reversed the improvement of silencing KLF5 on airway inflammation and pyroptosis in asthmatic mice. In conclusion, KLF5 inhibited miR-182–5p to promote TLR4 expression, thus aggravating pyroptosis and airway inflammation in asthmatic mice. • KLF5 is highly expressed in the lung tissue of asthmatic mice. • Silencing KLF5 reduces airway inflammation by inhibiting pyroptosis. • KLF5 inhibits the transcription and expression of miR-182–5p. • miR-182–5p targets and inhibits TLR4 expression. • KLF5 rises pyroptosis and airway inflammation via the miR-182–5p/TLR4 axis. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNA) dysregulation is demonstrated to be associated with disease progression. Mounting studies show that lncRNA promotes or inhibits the development of keloid. We aimed to disclose the role of homebox A11 antisense RNA (HOXA11-AS) in the formation of keloid. Quantitative real-time PCR (qPCR) was adopted for expression analysis of HOXA11-AS, miR-182-5p and zinc finger protein 217 (ZNF217) mRNA, and the expression of ZNF protein and marker proteins was detected by western blot. Cell proliferation, cell migration and cell apoptosis were investigated using CCK-8 assay, wound healing assay and flow cytometry assay, respectively. The potential interplay between miR-182-5p and HOXA11-AS or ZNF217 was verified by dual-luciferase reporter assay, RIP assay and pull-down assay. The role of HOXA11 in vivo was studied by establishing animal models. HOXA11-AS was highly expressed in tissues and fibroblasts of keloid. Deficiency of HOXA11-AS blocked the proliferation and migration of keloid fibroblasts and induced fibroblast apoptosis. HOXA11-AS directly combined to miR-182-5p whose downregulation reversed the effects of HOXA11-AS knockdown. ZNF217 was a target of miR-182-5p, and HOXA11-AS indirectly promoted ZNF217 expression by binding to miR-182-5p. MiR-182-5p enrichment also blocked keloid fibroblast proliferation, survival and migration, while further ZNF217 overexpression abolished these effects. HOXA11-AS knockdown also hindered the growth of keloid in mouse models. High expression of HOXA11-AS promoted the formation and growth of keloid through the upregulation of ZNF217 by targeting miR-182-5p, and the inhibition of HOXA11-AS might be a novel strategy to prevent keloid development. • The expression of HOXA11-AS is enhanced in keloid tissues and fibroblasts. • HOXA11-AS knockdown inhibits the proliferation, survival and motility of keloid fibroblasts. • HOXA11-AS targets miR-182-5p and thus promote the expression of ZNF217. • HOXA11-AS enhances ZNF217 expression by depleting miR-182-5p, leading to keloid fibroblast proliferation and migration, and keloid growth in vivo. [ABSTRACT FROM AUTHOR]

• CircGNAO1 was markedly downregulated in HCC. • CircGNAO1 inhibits HCC migration, invasion and proliferation. • Overexpression of circGNAO1 suppressed tumor metastasis and growth in vivo. • CircGNAO1 functions as a sponge for miR-182-5p to regulate FOXO1 expression and activate the TGF-β/Smad3 signaling pathway and EMT process. Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with poor prognosis. Using high-throughput sequencing, we identified a novel circRNA, circGNAO1, which is downregulated in HCC tissues compared to adjacent tissues. However, the potential functions and mechanisms of circGNAO1 in HCC metastasis remain unclear. qRT-PCR was used to detect the expression of circGNAO1, miR-182-5p, and FOXO1 in HCC cells and tissues. Bioinformatics analysis, RNA pull-down assyas, and dual-luciferase reporter assays were employed to verify the interaction between circGNAO1 and miR-182-5p. Functional experiments were conducted using circGNAO1 overexpression and knockdown cell lines, including Transwell, wound healing, and EdU assays. Liver metastasis models and subcutaneous xenograft mouse models were established to analyze the effect of circGNAO1 on HCC metastasis and growth in vivo. High-throughput sequencing and qRT–PCR results showed that the expression of circGNAO1 dramatically decreased in HCC tissues. Functionally, in vivo and in vitro experiments verified that overexpression of circGNAO1 inhibited the proliferation, migration, invasion and EMT of HCC cells, while knockdown of circGNAO1 promoted these behaviors. Mechanistically, we have demonstrated that circGNAO1 functions as a sponge for miR-182-5p to regulate FOXO1 expression, thereby activating the TGF-β/Smad3 signaling pathway and EMT process. circGNAO1 suppresses the progression and metastasis of HCC through the miR-182-5p/FOXO1 axis, and circGNAO1 may be an efficient therapeutic target in HCC. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are closely associated with the pathogenesis of numerous diseases including cancers. LncRNA AGAP2 Antisense RNA 1 (AGAP2-AS1) has been found to participate in the tumorigenesis of several kinds of human cancers. Nonetheless, its potential function in colorectal cancer (CRC) was still poorly investigated. The expression level of RNAs or proteins was assessed by RT-qPCR or western blot analysis. Functional experiments were performed to analyze the role of AGAP2-AS1 in CRC in vitro and in vivo. Mechanism investigations were fulfilled to determine the potential mechanism of the molecules. AGAP2-AS1 expression was significantly elevated in CRC cells and could be transcriptionally activated by E2F Transcription Factor 4 (E2F4). Down-regulated AGAP2-AS1 could weaken CRC cell growth, migration, invasion, and epithelial-mesenchymal transition (EMT). MicroRNA-182-5p (miR-182-5p) was the target downstream molecule of AGAP2-AS1. Furthermore, Cofilin 1 (CFL1) was proved as the target of miR-182-5p. Mechanically, AGAP2-AS1 could boost the CFL1 expression via competitively binding to miR-182-5p in CRC. Importantly, CFL1 restoration could counteract the in vitro and in vivo suppression of depleted AGAP2-AS1 on CRC progression. E2F4-stimulated AGAP2-AS1 aggravated CRC development through regulating miR-182-5p/CFL1 axis, implying that AGAP2-AS1 might become a potent new target for future therapies for CRC. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a severe psychiatric disorder with uncertain causes. Recent studies have indicated correlations between circular RNAs (circRNAs) and psychiatric disorders. However, the potential role of circRNAs in MDD remains largely unknown. We investigated the expression and diagnostic significance of circRNA protein tyrosine kinase 2 (circPTK2) by recruiting 50 MDD patients and 40 healthy subjects. Additionally, chronic unpredictable mild stress (CUMS) mouse model was established in animal experiments. QRT-PCR was adopted for circPTK2 and miR-182–5p levels. To investigate the role of circPTK2 in MDD, we utilized microinjection of circPTK2 adeno-associated virus into the mouse hippocampus. Depressive-like behaviors of mice were assessed through forced swim test and open field test. Additionally, the interaction between circPTK2 and miR-182–5p was validated using a dual luciferase reporter assay. Decreased expression of circPTK2 was found in peripheral blood mononuclear cells of MDD patients and in hippocampus of CUMS mice, which was useful for distinguishing MDD patients from healthy subjects. Notably, overexpression of circPTK2 was associated with depressive-like behaviors induced by CUMS. Further mechanism research demonstrated that circPTK2 functioned as the sponge for miR-182–5p, which may contribute to the beneficial effect of circPTK2. Collectively, our findings suggest the participation of circPTK2 and its underlying mechanism in MDD, which might provide a potential target for MDD therapy. • CircPTK2 was downregulated in MDD patients and in CUMS mice. • Overexpression of circPTK2 impact depressive-like behaviors induced by CUMS. • CircPTK2 might exerts its effects by sponging miR-182-5p. [ABSTRACT FROM AUTHOR]

• miR-182-5p downregulated the expression of TNFAIP8. • Overexpression of miR-182-5p improved cell viability and wound healing ability. • miR-182-5p targeted TNFAIP8 and regulated chondrocyte apoptosis and autophagy pathways. • ATG3 blocked the autophagy and apoptosis pathways induced through upregulation of TNFAIP8. • Exosome-derived miR-182-5p alleviated osteoarthritis by downregulating TNFAIP8. To investigate the role of exosomal miRNAs from synovial fluid (SF) in osteoarthritis (OA) patients and investigate the underlying molecular mechanism. Degenerated knee tissues were collected from male and female OA patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the differences in the expression of inflammatory indicators, including TNF-α, IL-6, and IL-10, between the degenerative and injury groups. Exosomes were isolated from SF using the Exoquick kit, and a microarray was used to identify differentially expressed miRNAs (DEmiRNAs), which were analyzed using bioinformatics. The predicted relationship between DEmiRNAs and target genes was verified using a luciferase reporter gene assay. CCK-8 and transwell assays were used to assess cell viability and migration. Immunofluorescence and TUNEL assay were used to detect cell autophagy and apoptosis. The interaction between proteins was detected by immunoprecipitation and verified by Mab rescue assay. The relative expression of TNF-α/IL6 was significantly higher in the degeneration group than in the injury group. The OA degeneration group released significantly more and smaller exosomes than the injury group. The expression of miR-182-5p was markedly reduced in OA patients and had a higher correlation with inflammatory indicators. Tumor necrosis factor α-induced protein 8 (TNFAIP8) was a target of miR-182-5p, and its overexpression promoted chondrocyte proliferation, migration, and invasion and enhanced the wound healing efficiency. We also found a direct interaction of TNFAIP8 with autophagy-related gene 3 (ATG3). TNFAIP8 triggered ATG3 LC3-mediated autophagy. The downregulation of exosomal miR-182-5p inhibits OA degeneration by targeting TNFAIP8 via the ATG/LC3 pathway. [ABSTRACT FROM AUTHOR]

• PDPN is a novel inflammation-associated biomarker in patients with viral myocarditis (VMC). • PDPN could help distinguish patients with VMC from those with acute myocardial infarction and healthy individuals. • PDPN might contribute to anti-heart autoantibody production to mediate myocardial injury via its ligand CCL-21 in VMC patients. • miR-182-5p/PDPN axis might be potential therapeutic target for VMC. Podoplanin (PDPN), a small mucin-like glycoprotein, was recently found to promote the generation of cardiac ectopic lymphoid follicles and anti-heart autoantibodies (AHA) in viral myocarditis (VMC) mice. Herein, we investigated the blood PDPN expression and its potential clinical value in VMC patients. Overall, 40 VMC patients were enrolled among 112 hospitalized patients with suspected myocarditis. Their serum PDPN levels were higher than those in controlled acute myocardial infarction (AMI) patients (n = 40) and healthy individuals (n = 30) (both p < 0.01) and positively correlated with CRP, IL-17, and IL-4 (all p < 0.01). Elevation of serum PDPN discriminated VMC from AMI (OR = 4.061, p < 0.01) and PDPN addition to the basic model (age, CRP, and peak cTNI) increased AUC values (from 0.822 to 0.933, p = 0.04). Additionally, the serum levels of PDPN ligand CCL-21 were also increased and correlated with PDPN (R = 0.59, p < 0.01) in VMC patients, accompanied by AHA production. Moreover, the anti-MHC antibody was closely related to PDPN levels (R = 0.53, p < 0.01), and anti-MHC-positive patients with VMC displayed higher percentages of CD4+IL-17A+PDPN+T cells and CD19+CCR7+B cells (both p < 0.05). Noticeably, VMC patients complicated by ventricular arrhythmias (27.50%) presented with AHA production and higher PDPN levels (p < 0.05). Finally, we screened out and verified that miR-182-5p directly targeted PDPN and negatively regulated its expression (all p < 0.01). These data suggested that blood PDPN might be a novel inflammation-associated biomarker for the early diagnosis of VMC and may contribute to AHA production by binding CCL-21 to recruit Th17 and B cells, which were regulated by miR-182-5p. [ABSTRACT FROM AUTHOR]

Abstract Increasing studies revealed that aberrant expression of long non-coding RNAs (lncRNAs) play critical roles in ovarian cancer (OC) progression. However, the roles and underlying mechanisms of ADAMTS9-AS2 in OC remain unclear. In the present study, we showed that ADAMTS9-AS2 expression was significantly decreased in OC tissues and cell lines. Low ADAMTS9-AS2 expression was correlated with advanced FIGO stage, lymph-node metastasis, and poor overall survival of OC patients. Function assays showed that ADAMTS9-AS2 reduced OC cells proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes in vitro and restrained tumor growth in vivo. The underlying mechanism studies indicated that ADAMTS9-AS2 functioned as a competing endogenous RNA (ceRNA) for miR-182-5p to promote cell proliferation and invasion. In addition, we revealed that FOXF2 acted as a direct target of miR-182-5p and mediated the effects of ADAMTS9-AS2 on OC cells progression. Taken together, our data suggested that lncRNA ADAMTS9-AS2 decreased OC progression by regulating miR-182-5p/FOXF2 axis, indicating ADAMTS9-AS2 could serve as a potential therapeutic target for OC treatment. [ABSTRACT FROM AUTHOR]

Our previous study has confirmed that constraint-induced movement therapy (CIMT) could promote neural remodeling in hemiplegic cerebral palsy (HCP) mice through Nogo-A/NgR/RhoA/ROCK signaling, however, the upstream mechanism was still unclear. Therefore, the present study aimed to further explore the mechanism of CIMT regulating the expression of Nogo-A in HCP mice. HCP mice were well established through ligating the left common carotid artery of 7-day-old pups and being placed in a hypoxic box which was filled with a mixture of 8% oxygen and 92% nitrogen. CIMT intervention was conducted by taping to fix the entire arm of the contralateral side (left) to force the mice to use the affected limb (right). Bioinformatics prediction and luciferase experiment were performed to confirm that miR-182–5p was targeted with Nogo-A. The beam test and grip test were applied to examine the behavioral performance under the intervention of c-Jun and CIMT. Also, immunofluorescence, Golgi staining, and transmission electron microscopy were conducted to show that the lenti-expression of c-Jun could increases the expression of myelin, and downregulates the expression of Nogo-A under the CIMT on HCP mice. (1) The beam walking test and grip test experiment results showed that compared with the control group, the HCP + nCIMT group's forelimb grasping ability and balance coordination ability were decreased (P < 0.05). (2) The results of Golgi staining, and transmission electron microscopy showed that the thickness of myelin sheath and the density of dendritic spines in the HCP + nCIMT group were lower than those in the control group (P < 0.05). Compared with the HCP + nCIMT group, the cerebral cortex myelin sheath thickness, dendrite spine density and nerve filament expression were increased in HCP + CIMT group (P < 0.05). (3) Immunofluorescence staining showed that the expression of Nogo-A in the cerebral cortex of the HCP + nCIMT group was higher than that of the HCP + CIMT group (P < 0.05). Compared with the HCP + CIMT group, the expression of Nogo-A in the HCP + LC + CIMT group was decreased and, in the HCP, + SC + CIMT group was significantly increased (P < 0.05). Compared with the HCP + nCIMT group, the expression of c-Jun in the control, HCP + CIMT, HCP + LC + nCIMT and HCP + LC + CIMT groups was significantly increased, and in the HCP + SC + CIMT was decreased (P < 0.05). (4) Real-time quantitative polymerase chain reaction (RT-qPCR) results showed that the expression level of miR-182–5p in the HCP + LC + CIMT group was more increased than that in the HCP + nCIMT group (P < 0.05). The expression level of miR-182–5p in the HCP + LC + CIMT group was higher than that in the HCP + LC + nCIMT group and the HCP + SC + CIMT group (P < 0.05). These data identified that CIMT might stimulate the remodeling of neurons and myelin in the motor cortex by partially inhibiting the c-Jun/miR-182–5p/Nogo-A pathway, thereby facilitating the grasping performance and balance function of HCP mice. [ABSTRACT FROM AUTHOR]

The importance of microRNAs (miRNAs) are shown during various cancers including acute myeloid leukemia (AML). MiR-182-5p functions as an oncogene or a potential suppressive miRNA in cancers, but its expression and function in AML is unknown. The purpose is to investigate the roles of miR-182-5p in AML in this study. MiR-182-5p was examined in the blood samples of AML and it was found that miR-182-5p expression levels were higher in AML tissues than it in their normal controls, so did in the AML cells. BCL2L12 and BCL2 were predicted as target genes of miR-182-5p and verified using luciferase reporter assay. BCL2L12 and BCL2 mRNA and protein levels were up-regulated in the AML cells with miR-182-5p inhibition. Cellular function of miR-182-5p indicated that miR-182-5p suppression in AML cells could decrease cell proliferation and reverse cisplatin (DDP) resistance via targeting BCL2L12 and BCL2 expression. Inhibition of miR-182-5p promoted AML cell apoptosis by targeting BCL2 or BCL2L12. The study demonstrates that high levels of miR-182-5p in AML promotes cell proliferation and suppresses cell apoptosis by targeting BCL2L12 and BCL2. [ABSTRACT FROM AUTHOR]

Background: Toll-like receptor 4 (TLR4) plays a critical role in ischemic brain injury by mediating the inflammatory response. The microRNA miR-185-5p suppresses inflammatory signaling by targeting TLR4. This study investigates whether overexpressing miR-182-5p in bone marrow-derived mesenchymal stem cells (BM-MSCs) could potentiate the neuroprotective effects of BM-MSCs in a mouse model of ischemic brain injury.Methods: We isolated BM-MSCs from mice, transfected the cells with miR-182-5p mimic, determined their MSC lineage through flow cytometry analysis of surface markers, examined miR-182-5p and TLR4 expression levels, and injected them into mice undergone middle cerebral artery occlusion (MCAO). MSC transplanted mice were subjected to behavior assays to determine cognitive and motor functions and biochemical analysis to determine neuroinflammation and TLR4/NF-κB in the ischemic hemisphere.Results: We found that BM-MSCs overexpressing miR-182-5p showed reduced TLR4 expression without affecting their MSC lineage. Mice transplanted with miR-182-5p overexpressing BM-MSCs after MCAO showed significantly improved cognitive and motor functions and reduced neuroinflammation, including suppressed microglial M1 polarization, reduced inflammatory cytokines, and inhibited TLR4/ NF-κB signaling.Conclusion: Our findings suggest that overexpressing miR-182-5p in BM-MSCs can enhance the neuroprotective effects of BM-MSCs against ischemic brain injury by suppressing TLR4-mediated inflammatory response. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic heavy metal pollutant that can be accumulated in organs including the spleen, thereby threatening human health. In this study, the effect of caffeic acid phenethyl ester (CAPE, a bioactive component of honeybee propolis) on CdCl 2 -induced spleen toxicity and underlying mechanisms were examined in mice. Histological examinations revealed that CAPE (10 μmol/kg/day b.w.) could mitigate spleen damage induced by CdCl 2 (1.5 mg/kg/day b.w.) in mice. Compared to the mice treated only by CdCl 2 , CAPE administration increased the body weight while decreasing the spleen weight, spleen Cd content and spleen to body ratio of the CdCl 2 -treated mice. Western blot and ELISA tests revealed that CAPE suppressed CdCl 2 -induced inflammation (indicated by the decreases in the levels of inflammatory indictors). TUNEL and Western blot results showed that CAPE suppressed CdCl 2 -induced apoptosis through reducing the percentage of TUNEL-positive cells and regulating apoptosis factors. The antagonistic effect of CAPE against CdCl 2 -induced spleen toxicity was realized by increasing miR-182–5p expression to regulate the TLR4/NF-κB pathway. Therefore, CAPE could be a food-derived spleen protector to counteract Cd-induced spleen toxicity through alleviating apoptosis and inflammation via the miR-182–5p/TLR4/NF-κB axis. • Cadmium causes spleen damage via inducing inflammation and apoptosis in mice. • Cd exposure increases the levels of TLR4 and decreases the level of miR-182–5p. • CAPE plays a protective role against Cd induced spleen injury via TLR4/NFκB pathway. • MiR-182–5p targets TLR4 to involve in the protective process of CAPE. [ABSTRACT FROM AUTHOR]

RBP-J is involved in number of cellular processes. However, the potential mechanisms of RBP-J on colorectal cancer (CRC) development have not been clearly defined. In this study, we aimed to investigate the role and molecular mechanism of RBP-J in CRC. The expression levels of RBP-J and Tiam1 in CRC tissues and cells were evaluated by RT-qPCR or western blot. RBP-J was knocked down with sh-RBP-J or overexpressed by pcDNA3.1-RBP-J in CRC cells. Cell proliferation, migration and invasion abilities were analyzed by MTT, wound healing, and transwell assay, respectively. CHIP-qPCR, RIP and dual luciferase reporter assays were performed to confirm the interaction between miR-182-5p and RBP-J or Tiam1. Expression levels of p-p38 MAPK, p38 MAPK, Slug-1, Twist1 and MMP-9 were analyzed by western blot. G-LISA test was used to detect Rac1 activity. Our results showed that the expression of RBP-J and Tiam1 was significantly up-regulated in CRC tissues and cells. RBP-J overexpression promoted proliferation, migration and invasion of CRC cells. Moreover, RBP-J was found to directly target miR-182-5p promoter and positively regulate the Tiam1/Rac1/p38 MAPK signaling pathway in CRC cells. It was also proved that miR-182-5p can bind Tiam1 directly. Furthermore, experiments revealed that RBP-J could promote CRC cell proliferation, migration and invasion via miR-182-5p-mediated Tiam1/Rac1/p38 MAPK axis. In addition, knockdown of RBP-J reduced tumor growth and metastasis in CRC mice. RBP-J regulates CRC cell growth and metastasis through miR-182-5p mediated Tiam1/Rac1/p38 MAPK signaling pathway, implying potential novel therapeutic targets for CRC patients. • RBP-J and Tiam1 were dysregulated in colorectal cancer tissues and cells. • RBP-J promoted the growth and metastasis of colorectal cancer cells. • RBP-J positively regulated the Tiam1/Rac1/p38 MAPK signaling pathway. • RBP-J exerted its function via miR-182-5p-mediated Tiam1/Rac1/p38 MAPK axis. [ABSTRACT FROM AUTHOR]

Chronic neuropathic pain is characterized by neuroinflammation. Previously, long noncoding RNA (lncRNA) HAGLR was reported to regulate the inflammatory response of SH-SY5Y cells. However, neither the specific function nor the potential mechanism of HAGLR in neuropathic pain has been explored. Our study is aimed to figure out the role of HAGLR in neuropathic pain. SH-SY5Y cells were treated with lipopolysaccharide (LPS) to mimic neuron injury in vitro. The chronic constriction injury (CCI) rat models were established by ligation of sciatic nerve to mimic neuropathic pain in vivo. Behavioral assessment assays were performed to determine the effects of HAGLR on hypersensitivity in neuropathic pain. Enzyme-linked immunosorbent assay kits were used for detection of inflammatory cytokines. Flow cytometry analysis and Western blot were applied to detect apoptosis. HAGLR displayed high levels in spinal cords of CCI rats and in LPS treated SH-SY5Y cells. Knockdown of HAGLR inhibited inflammation and neuron apoptosis of LPS treated SH-SY5Y cells. Mechanistically, HAGLR bound with miR-182–5p in SH-SY5Y cells. ATAT1 served as a target of miR-182–5p. HAGLR activated the NLRP3 inflammasome by ATAT1. Rescue assays demonstrated that overexpression of ATAT1 or NLRP3 reversed the suppressive effects of HAGLR silencing on apoptosis and inflammatory response in SH-SY5Y cells and in spinal cords of CCI rats. The inhibitory effects of silenced HAGLR on hypersensitivity in neuropathic pain were also rescued by ATAT1 or NLRP3. HAGLR aggravates neuropathic pain by sequestering miR-182–5p from ATAT1 and activating NLRP3 inflammasome, which may provide a potential therapeutic target for neuropathic pain treatment. • Upregulated HAGLR facilitated inflammatory response and apoptosis of SH-SY5Y cells. • HAGLR bound with miR-182–5p to upregulate ATAT1 in SH-SY5Y cells. • HAGLR activated NLRP3 inflammasome by upregulation of ATAT1 in SH-SY5Y cells. • ATAT1 or NLRP3 reversed the effects of HAGLR silencing on apoptosis and inflammatory response of SH-SY5Y cells. • Overexpression of ATAT1 or NLRP3 offset the effects of HAGLR silencing on neuropathic pain in CCI rats. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is one of the significant chronic inflammatory pathology considering public health impact. Up-regulation of HDAC1 has been proved to be related with endothelial dysfunction which is correlated intimately with AS. Our research aims to investigate how histone deacetylase 1 (HDAC1)/miR-182-5p/vav guanine nucleotide exchange factor 3 (VAV3)/AKT axis participates in AS in terms of molecular mechanism. We detected miR-181-5p in human umbilical vein endothelial cells after treatment with aorta and ox-LDL in AS model mice. Dual luciferase reporter assay was employed to verify interaction of miR-182-5p and VAV3. ChIP was performed to determine the relationship between HDAC1 and promoter of miR-182-5p. Protein levels of HADC1, VAV3, AKT, p-AKT, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein 1 (MCP-1) were detected by western blot analysis. CCK8 and flow cytometry were used to detect cell viability and apoptosis, respectively. After different treatments, the ability of cells to form monoclonal cells was detected, and AS was evaluated by detecting arterial injury and inflammation-related factors. Overexpression of HDAC1 could inhibit HUVECs proliferation and promote AS in mouse model. It was verified by dual luciferase assay that miR-182-5p could bind to VAV3 3′UTR mRNA. Meanwhile, HDAC1 repressed miR-182-5p expression through binding to miR-182-5p promoter and then inhibit VAV3 expression further. In summary, HDAC1 promoted AS through AKT pathway, which was improved by VAV3 activation mediated by miR-182-5p. Our results demonstrated that HDAC1 repressed miR-182-5p and activating AKT pathway via improving VAV3 to promote AS progression. • HDAC1 upregulates VAV3 expression via miR-182-5p. • HDAC1 promotes atherosclerosis through binding to miR-182-5p to inhibit HUVECs proliferation. • HDAC1 activates AKT pathway by upregulating VAV3. [ABSTRACT FROM AUTHOR]

• Matrine inhibits miR-182-5p expression and induces apoptosis of PTC cells. • Overexpression of miR-182-5p abolishes the marine-induced apoptosis of PTC cells. • Matrine‑suppressed tumor growth were attenuated after miR-182-5p was overexpressed. • Matrine suppresses tumor growth in vivo by inducing apoptosis of PTC cells. Matrine is a natural product extracted from the root of Sophora flavescens that has been shown to be a promising alternative drug in different types of cancer. Here, we aimed to investigate the antitumor effects of matrine on human papillary thyroid cancer (PTC) and explore the underlying molecular mechanisms. Our data demonstrated the following findings. (a) The expression of miR-182-5p was significantly upregulated in PTC tissues and cell lines. (b) Matrine inhibited the expression of miR-182-5p and induced the apoptosis of TCP-1 and BCPAP cells in a dose-dependent manner. (c) Matrine increased caspase3 expression levels and reduced Bcl-2 expression levels in both TCP-1 and BCPAP cells. (d) Matrine appreciably inhibited PTC tumor growth in vivo. (e) After miR-182-5p overexpression, matrine-induced apoptosis and caspase3 activation were inhibited, and the matrine-induced decrease in Bcl-2 expression was abolished. (f) Overexpression of miR-182-5p counteracted the inhibitory effects of matrine on PTC tumor growth. In conclusion, these results demonstrate that matrine exerts antitumor effects possibly by inducing the apoptosis of TCP-1 and BCPAP cells, decreasing the level of Bcl-2, activating caspase3 and suppressing PTC tumor growth by downregulating the expression of miR-182-5p. These findings explain the anticancer mechanisms of matrine in PTC and identify miR-182-5p as an effective target of matrine in PTC treatment. [ABSTRACT FROM AUTHOR]

• TNF-α exposure reduces miR-182-5p expression in ASM cells. • miR-182-5p inhibits ASM cell proliferation and migration. • TRIM8 is a target gene of miR-182-5p. • miR-182-5p inhibits NF-κB by targeting TRIM8. MicroRNAs (miRNAs) have emerged as critical modulators involved in the regulation of airway remodeling in asthma. MicroRNA-182-5p (miR-182-5p) has been reported as a key miRNA in regulating the proliferation and migration of various cell types, and its dysfunction contributes is implicated in a wide range of pathological processes. Yet, it remains unknown whether miR-182-5p modulates the proliferation and migration of airway smooth muscle (ASM) cells during asthma. In the present study, we aimed to determine the potential role of miR-182-5p in regulating the proliferation and migration of ASM cells induced by tumor necrosis factor (TNF)-α in vitro. We found that TNF-α stimulation markedly reduced miR-182-5p expression in ASM cells. Gain-of-function experiments showed that miR-182-5p upregulation suppressed the proliferation and migration of ASM cells induced by TNF-α. By contrast, miR-182-5p inhibition had the opposite effect. Notably, tripartite motif 8 (TRIM8) was identified as a target gene of miR-182-5p. TRIM8 expression was induced by TNF-α stimulation, and TRIM8 knockdown markedly impeded TNF-α-induced ASM cell proliferation and migration. Moreover, miR-182-5p overexpression or TRIM8 knockdown significantly downregulated the activation of nuclear factor-κB (NF-κB) induced by TNF-α. However, TRIM8 restoration partially reversed the miR-182-5p-mediated inhibitory effect on TNF-α-induced ASM cell proliferation and migration. In conclusion, our study indicates that miR-182-5p restricts TNF-α-induced ASM cell proliferation and migration through downregulation of NF-κB activation via targeting TRIM8. The results of our study highlight the potential importance of the miR-182-5p/TRIM8/NF-κB axis in the airway remodeling of asthma. [ABSTRACT FROM AUTHOR]