Serum mir-142-3p release in children with viral encephalitis and its relationship with nerve injury and inflammatory response.

BACKGROUND: Viral encephalitis (VE) is a common infectious disease of the central nervous system in children. Children with severe disease may have progressive neurological damage and even lead to death. AIMS: To assess the serum miR-142-3p levels in children with VE and the correlation between miR-142-3p and the severity and prognosis of VE. Besides, its relationship with nerve injury and inflammatory response was assessed. METHODS: Children with VE were regarded as a case group and healthy children served as control. The content of serum miR-142-3p was determined using real-time quantitative PCR. The risk factors associated with severity and prognosis of cases were evaluated using logistic analysis. The discrepancy in miR-142-3p levels, nerve injury-related indicators, and inflammatory cytokines were contrasted among groups. The ROC curve was conducted to assess the diagnostic performance of serum miR-142-3p in predicting prognosis of children with VE. RESULTS: The altered expression of miR-142-3p in serum of children with VE was enhanced in contrast to healthy control. Serum nerve injury indicators MBP, ß-EP, and NSE levels and serum inflammatory cytokines IL-6, IL-18, and IFN-γ were high in children with VE in contrast to healthy control, and had positive relevance with serum miR-142-3p. Besides, serum miR-142-3p was a risk factor associated with the severity and prognosis of children with VE. Serum miR-142-3p had diagnostic performance in predicting the prognosis of children with VE. CONCLUSION: Serum miR-142-3p content is high in children with VE and maybe a diagnosis marker for predicting prognosis. The specific miR-142-3p expression may be directly related to the severity of nerve injury and inflammatory response for VE.

Inhibition of miR-142-3p promotes intestinal epithelial proliferation and barrier function after ischemia/reperfusion injury by targeting FoxM1.

Damage of intestinal barrier function (BF) after ischemia/reperfusion (I/R) injury can induce serious complications and high mortality. MicroRNAs (miRNAs) are involved in intestinal mucosal BF and epithelial proliferation after I/R injury have been reported. We aimed to investigate the role and regulatory mechanism of miR-142-3p (miR-142) in intestinal epithelial proliferation and BF after I/R injury. We detected the proliferation, barrier function and miR-142 expression in clinical ischemic intestinal tissues. Furthermore, we induced an in vivo intestinal I/R injury mouse model and in vitro IEC-6 cells hypoxia/reoxygenation (H/R) injury model. After increasing and decreasing expression of miR-142, we detected the proliferation and barrier function of intestinal epithelial cells after I/R or H/R injury. We found that miR-142 expression was significantly increased in clinical ischemic intestinal mucosa and mouse intestinal mucosa exposed to I/R injury, and there was an inverse relationship between miR-142 and proliferation/BF. Inhibition of miR-142 significant promoted intestinal epithelial proliferation and BF after I/R injury. Furthermore, inhibition of miR-142 improved overall survival rate of mice after I/R injury. MiR-142 directly targeted FoxM1 which was identified by bioinformatics analysis and luciferase activity assay in IEC-6 cells. Inhibition of miR-142 promotes intestinal epithelial proliferation and BF after I/R injury in a FoxM1-mediated manner.

The Correlation Between Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) and miR-142-3p in Maintenance Hemodialysis Patients With End-Stage Renal Disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) are at high risk for major adverse cardiovascular and cerebrovascular events (MACCE), which are prone to be detrimental to patients' lives. Identifying risk factors for MACCE can help target measures to prevent or reduce the occurrence of MACCE. OBJECTIVE: The aim was to investigate the correlation between miR-142-3p and MACCE in ESRD patients on MHD and to provide a new predictor for MACCE occurrence. METHODS: Blood samples were collected from subjects to detect the expression of miR-142-3p using RT-qPCR. The correlation of miR-142-3p with HDL-C and hs-CRP was assessed by the Pearson method. The occurrence of MACCE in patients during the 36-month follow-up period was recorded. The clinical value of miR-142-3p in MACCE occurrence was analyzed by the Kaplan-Meier curve, multivariate logistic regression, and ROC curve. RESULTS: In ESRD patients on MHD, miR-142-3p was downregulated, and it showed a positive correlation with HDL-C but a negative correlation with hs-CRP. The cumulative incidence of MACCE at 1, 2, and 3 years was 8.9%, 20.0%, and 30.4%, respectively. miR-142-3p levels were reduced in patients who developed MACCE and were associated with the cumulative incidence of MACCE. miR-142-3p was a risk factor for MACCE and showed a predictive value with specificity and sensitivity of 89.36% and 56.10%, respectively. CONCLUSIONS: miR-142-3p was a risk factor of MACCE in ESRD patients undergoing MHD.

"Decoding inflammation: glycoprotein a repetition predominant, microRNA-142-3-p, and metastasis associated lung adenocarcinoma transcript 1: as novel inflammatory biomarkers of inflammatory bowel disease".

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-ß (TGF-ß) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD. METHODS: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed. RESULTS: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores. CONCLUSIONS: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-ß. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment.

miR-142-3p/5p role in cancer: From epigenetic regulation to immunomodulation.

MicroRNAs (miRNAs) play critical roles in cancer pathobiology, acting as regulators of gene expression and pivotal drivers of tumorigenesis. It is believed that miRNAs act through canonical mechanisms, involving the binding of mature miRNAs to target messenger RNAs (mRNAs) and subsequent repression of protein translation or degradation of target mRNAs. miR-142-3p/5p has been extensively studied and established as a key regulator in various malignancies. Recent discoveries have revealed miR-142-3p/5p serve as either oncogene or tumor suppressor in cancer. By targeting epigenetic factor and cancer-related signaling pathway, miR-142-3p/5p can regulate wide range of downstream genes. The immune modulatory role of miR-142-3p/5p has been shown in various cancers, which provides significant insight into immunosuppression and tumor escape from the immune response. Exosomes with miR-142-3p/5p facilitate cell communication and can affect cancer cell behavior, offering potential therapeutic, and diagnosis applications in cancer therapy. In this review, for the first time, we comprehensively summarize the current knowledge regarding mentioned functions of miR-142-3p/5p in cancer pathobiology.

CircTAOK1 regulates high glucose induced inflammation, oxidative stress, ECM accumulation, and apoptosis in diabetic nephropathy via targeting miR-142-3p/SOX6 axis.

BACKGROUND: Diabetic nephropathy (DN) is a complication caused by diabetes. Circular RNAs (circRNAs) are a kind of RNA with a closed circular structure, which has high stability and is involved in many disease-related processes. The mechanism of circRNA TAO kinase 1 (circTAOK1) in the pathogenesis and development of DN is unclear. METHODS: CircTAOK1, microRNA (miR)-142-3p, and sex-determining region Y-box transcription factor 6 (SOX6) mRNA levels were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to analyze cell proliferation. Cell cycle distribution was detected by flow cytometry. Western blot assay was performed to test B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cleaved-caspase 3, and fibronectin (FN), collagen I (Col I), and collagen IV (Col IV) protein levels. ELISA assay was used to measure interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activity were assessed by the corresponding kits. And the correlation between miR-142-3p and circTAOK1 or SOX6 was confirmed by dual luciferase reporter assay, RNA immunoprecipitation assay and RNA pull down assay. RESULTS: CircTAOK1 and SOX6 expression levels were up-regulated, while miR-142-3p expression was down-regulated in DN serum and HG-treated HK-2 cells. Knockdown of circTAOK1 could inhibit cell injury of HG-induced HK-2 cells. The inhibitory effect of circTAOK1 knockdown on HG-induced HK-2 cell injury was restored by miR-142-3p downregulation. CircTAOK1 acted as a sponge for miR-142-3p, and SOX6 was targeted by miR-142-3p. The overexpression of SOX6 could recover the effect of miR-142-3p overexpression on HG-induced HK-2 cell injury. CircTAOK1 regulated the expression of SOX6 by targeting miR-142-3p. CONCLUSION: CircTAOK1 knockdown inhibited HG-induced HK-2 cell damage in DN by the miR-142-3p/SOX6 axis.

Hypervolemia in Dialysis Patients Impairs STAT3 Signaling and Upregulates miR-142-3p: Effects on IL-10 and IL-6.

Fluid overload in hemodialysis patients (HD) has been proven to be associated with inflammation. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) appear to be inadequately counterbalanced by the anti-inflammatory cytokine interleukin-10 (IL-10). We initiated a cross-sectional study enrolling 40 HD patients who were categorized by a bioimpedance measurement in normovolemic (N; 23) and hypervolemic (H; 17) groups to test whether IL-10- and IL-6-related signal transduction pathways (signal transducer of transcript 3: STAT3) and/or a post-transcriptional regulating mechanism (miR-142) are impaired by hypervolemia. IL-10/IL-6 transcript and protein production by PBMCs (peripheral blood mononuclear cells) were determined. Phospho-flow cytometry was used to detect the phosphorylated forms of STAT3 (pY705 and pS727). miR-142-3p/5p levels were detected by qPCR. Hypervolemic patients were older, more frequently had diabetes, and showed higher CRP levels. IL-10 transcripts were elevated in H patients but not IL-10 protein levels. In spite of the elevated mRNA expression of the suppressor of cytokine expression 3 (SOCS3), IL-6 mRNA and protein expression were increased in immune cells of H patients. The percentage of cells staining positive for STAT3 (pY705) were comparable in both groups; in STAT3 (pS727), however, the signal needed for full transactivation was decreased in H patients. miR-142-3p, a proven target of IL-10 and IL-6, was significantly elevated in H patients. Insufficient phosphorylation of STAT3 may impair inflammatory and anti-inflammatory cytokine signaling. How far degradative mechanisms induced by elevated miR-142-3p levels contribute to an inefficient anti-inflammatory IL-10 signaling remains elusive.

[Expression of miR-142 and its relationship with Th17/Treg imbalance in children with autoimmune thyroid disease]. / miR-142åœ¨å„¿ç«¥è‡ªèº«å ç–«æ€§ç”²çŠ¶è ºç–¾ç— ä¸­è¡¨è¾¾åŠä¸ŽTh17/Tregå¤±è¡¡å ³ç³»çš„ç ”ç©¶.

OBJECTIVES: To investigate the expression of microRNA-142 (miR-142) in children with autoimmune thyroid disease (AITD) and its relationship with the imbalance of helper T cell 17 (Th17) and regulatory T cell (Treg). METHODS: A total of 89 children hospitalized for AITD from January 2019 to December 2022 were prospectively selected as the study subjects, including 48 children with Graves' disease (GD group) and 41 children with Hashimoto's thyroiditis (HT group). Additionally, 55 healthy children undergoing physical examinations during the same period were selected as the control group. The differences in serum miR-142, antithyroglobulin antibody (TGAb), antithyroperoxidase antibody (TPOAb), Th17/Treg, and interleukin-17 (IL-17) expression were compared among the groups. RESULTS: The expression of miR-142, TPOAb, TGAb, Th17, Th17/Treg, and IL-17 in the GD group and HT group was higher than that in the control group, while Treg was lower than that in the control group (P<0.05). Pearson correlation analysis revealed that in the GD group, miR-142 was positively correlated with TPOAb, TGAb, Th17, Th17/Treg, and IL-17 (r=0.711, 0.728, 0.785, 0.716, 0.709, respectively; P<0.001) and negatively correlated with Treg (r=-0.725, P<0.001); in the HT group, miR-142 was positively correlated with TPOAb and TGAb (r=0.752, 0.717, respectively; P<0.001). CONCLUSIONS: miR-142 is highly expressed in children with AITD, and its expression may be related to the Th17/Treg imbalance in children with GD.

A gain-of-function mutation in microRNA 142 is sufficient to cause the development of T-cell leukemia in mice.

MicroRNAs (miRNAs) play a crucial role in regulating gene expression. MicroRNA expression levels fluctuate, and point mutations and methylation occur in cancer cells; however, to date, there have been no reports of carcinogenic point mutations in miRNAs. MicroRNA 142 (miR-142) is frequently mutated in patients with follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia (CLL), and acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). To understand the role of miR-142 mutation in blood cancers, the CRISPR-Cas9 system was utilized to successfully generate miR-142-55A>G mutant knock-in (Ki) mice, simulating the most frequent mutation in patients with miR-142 mutated AML/MDS. Bone marrow cells from miR-142 mutant heterozygous Ki mice were transplanted, and we found that the miR-142 mutant/wild-type cells were sufficient for the development of CD8+ T-cell leukemia in mice post-transplantation. RNA-sequencing analysis in hematopoietic stem/progenitor cells and CD8+ T-cells revealed that miR-142-Ki/+ cells had increased expression of the mTORC1 activator, a potential target of wild-type miR-142-3p. Notably, the expression of genes involved in apoptosis, differentiation, and the inhibition of the Akt-mTOR pathway was suppressed in miR-142-55A>G heterozygous cells, indicating that these genes are repressed by the mutant miR-142-3p. Thus, in addition to the loss of function due to the halving of wild-type miR-142-3p alleles, mutated miR-142-3p gained the function to suppress the expression of distinct target genes, sufficient to cause leukemogenesis in mice.

PAX5-miR-142 feedback loop promotes breast cancer proliferation by regulating DNMT1 and ZEB1.

BACKGROUND: Breast cancer is one of the most common malignancies occurred in female around the globe. Recent studies have revealed the crucial characters of miRNA and genes, as well as the essential roles of epigenetic regulation in breast cancer initiation and progression. In our previous study, miR-142-3p was identified as a tumor suppressor and led to G2/M arrest through targeting CDC25C. However, the specific mechanism is still uncertain. METHODS: We identified PAX5 as the upstream regulator of miR-142-5p/3p through ALGGEN website and verified by series of assays in vitro and in vivo. The expression of PAX5 in breast cancer was detected by qRT-PCR and western blot. Besides, bioinformatics analysis and BSP sequencing were performed to analyze the methylation of PAX5 promoter region. Finally, the binding sites of miR-142 on DNMT1 and ZEB1 were predicted by JASPAR, and proved by luciferase reporter assay, ChIP analysis and co-IP. RESULTS: PAX5 functioned as a tumor suppressor by positive regulation of miR-142-5p/3p both in vitro and in vivo. The expression of PAX5 was regulated by the methylation of its promoter region induced by DNMT1 and ZEB1. In addition, miR-142-5p/3p could regulate the expression of DNMT1 and ZEB1 through binding with their 3'UTR region, respectively. CONCLUSION: In summary, PAX5-miR-142-DNMT1/ZEB1 constructed a negative feedback loop to regulate the progression of breast cancer, which provided emerging strategies for breast cancer therapy.

Downregulation of circ-YES1 suppresses NSCLC migration and proliferation through the miR-142-3p-HMGB1 axis.

BACKGROUND: Circular RNAs (circRNAs) are a new family of abundant regulatory RNAs with roles in various types of cancer. While the hsa_circ_0046701 (circ-YES1) function in non-small cell lung cancer (NSCLC) is unclear. METHODS: Circ-YES1 expression in normal pulmonary epithelial and NSCLC cells was examined. The small interfering RNA for circ-YES1 was prepared, cell proliferation and migration were assessed. Tumorigenesis in nude mice was assayed to validate the role of circ-YES1. Bioinformatics analyses and luciferase reporter assays were utilized to identify downstream targets of circ-YES1. RESULTS: Compared to normal pulmonary epithelial cells, the circ-YES1 expression increased in NSCLC cells, and cell proliferation and migration were suppressed after circ-YES1 knockdown. Both high mobility group protein B1 (HMGB1) and miR-142-3p were found to be downstream targets of circ-YES1, and miR-142-3p inhibition and HMGB1 overexpression reversed the effects of circ-YES1 knockdown on cell proliferation and migration. Similarly, HMGB1 overexpression reversed the miR-142-3p overexpression effects on these two processes. The imaging experiment results revealed that circ-YES1 knockdown impeded tumor development and metastasis in a nude mouse xenograft model. CONCLUSION: Taken together, our results show that circ-YES1 promotes tumor development through the miR-142-3p-HMGB1 axis and support the development of circ-YES1 probability as a new therapeutic NSCLC target.

Silencing lncRNA KCNQ1OT1 reduced hepatic ischemia reperfusion injury-induced pyroptosis by regulating miR-142a-3p/HMGB1 axis.

BACKGROUND: Based on pre-existing evidence, KCNQ1OT1 has been pointed out to be closely related to myocardial and cerebral ischemia reperfusion injury diseases. Herein, the objective of our study is to probe into the potential function as well as the underlying mechanism of KCNQ1OT1 on hepatic ischemia reperfusion injury (HIRI). METHODS: Using C57BL/6 J mice and primary mouse hepatocytes were conducted to establish HIRI model in vivo and in vitro. Cell viability was examined using CCK-8 assay and EdU assay. Flow cytometric analysis was performed to evaluate the pyroptosis. Dual-luciferase reporter assay was employed to verify the interaction relationships. qRT-PCR and Western blot were adopted to analyze the mRNA and protein level. Histopathological alteration of liver tissue was evaluated by HE staining. Immunohistochemistry (IHC) was performed to measure NLRP3 and caspase 1. RESULTS: Our data revealed that KCNQ1OT1 expression was ascending in hepatic tissue of HIRI mouse. Moreover, deprivation of KCNQ1OT1 mitigated I/R-induced hepatic injury and pyroptosis in vivo. Further experiments demonstrated that silencing KCNQ1OT1 promoted proliferation and inhibited pyroptosis in hypoxia/reoxygenation (H/R)-induced primary mouse hepatocytes. Mechanistically, KCNQ1OT1 functioned as a competing endogenous RNA which sponged miR-142a-3p, therefore promoted HMGB1 expression to activate TLR4/NF-κB signaling pathway in HIRI. CONCLUSION: LncRNA KCNQ1OT1 elevated HMGB1 expression through binding to miR-142a-3p, thereby promoting pyroptosis in HIRI.

miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV.

INTRODUCTION: Malignant mesothelioma is an aggressive cancer associated with asbestos exposure. Currently, the efficacy of therapeutics is limited in malignant mesothelioma, and developing more effective therapies is the need of the hour. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have attracted attention as therapeutic targets. To explore potential therapeutic targets, we focused on miR-142-3p expression, which was found to be significantly downregulated in mesothelioma cell lines in our previous study. METHODS: Mesothelioma cell lines and tissues were validated for expression of miR-142-3p or integrin subunit alpha-V (ITGAV). We transfected mesothelioma cell lines with miR-142-3p mimic and ITGAV siRNA and analyzed their biological functions. RESULTS: We found that miR-142-3p was significantly downregulated in mesothelioma tissues. Transfection with miR-142-3p mimic significantly suppressed cell proliferation, migration, and invasion. Bioinformatics analysis of potential targets of miR-142-3p identified ITGAV. Membrane ITGAV expression in mesothelioma cell lines was confirmed using immunocytochemistry. ITGAV was significantly upregulated in mesothelioma tissues. Moreover, transfection of miR-142-3p mimics into mesothelioma cell lines significantly suppressed ITGAV expression, indicating that miR-142-3p targets ITGAV. Next, ITGAV siRNA transfection into mesothelioma cell lines inhibited cell proliferation, migration, and invasion. Further investigation of cell adhesion mechanisms showed that the miR-142-3p/ITGAV axis specifically affects mesothelioma cell adhesion via vitronectin in the extracellular matrix. CONCLUSION: This study proposed that the miR-142-3p/ITGAV axis is involved in tumor progression in malignant mesothelioma.

Protective role of circRNA CCND1 in ulcerative colitis via miR-142-5p/NCOA3 axis.

BACKGROUND: Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues. METHODS: Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1, miR-142-5p, and nuclear receptor coactivator-3 (NCOA3) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1ß, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits. RESULTS: CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1. Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1-plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si-NCOA3. CONCLUSION: CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.

Silencing of circ-NT5C2 retards the progression of IL-1ß-induced osteoarthritis in an in vitro cell model by targeting the miR-142-5p/NAMPT axis.

Osteoarthritis (OA) is a degenerative disease that occurs mostly in the elderly, and its specific pathogenesis is still unknown, but recent studies have found that circular RNA generally display aberrant expression in OA. Our study explored the expression characteristics and mechanism of action of circ-NT5C2 in OA. Circ-NT5C2, microRNA-142-5p (miR-142-5p), and nicotinamide phosphoribosyltransferase (NAMPT) mRNA levels were measured using RT-qPCR. Western blot was employed to assess the protein level of NAMPT and extracellular matrix (ECM) production-related markers. The viability, proliferation, apoptosis and inflammation were examined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Relationship between miR-142-5p and circ-NT5C2 or NAMPT was demonstrated by dual-luciferase reporter system and RNA immunoprecipitation assay. We reported that circ-NT5C2 and NAMPT were greatly upregulated, and miR-142-5p level was constrained in OA tissues and in a cell model. Circ-NT5C2 silencing alleviated IL-1ß-induced inhibitory effects on chondrocyte proliferation and ECM generation, meanwhile the promotional role of IL-1ß on chondrocyte apoptosis and inflammation was also weakened. The targeting relationship of miR-142-5p with either circ-NT5C2 or NAMPT was confirmed. Knockdown of miR-142-5p reversed the suppressive effects of circ-NT5C2 silencing on the OA progression in vitro, and NAMPT overexpression also attenuated the effects of miR-142-5p upregulation in an OA cell model. Collectively, circ-NT5C2 accelerated the OA process by targeting the miR-142-5p/NAMPT axis. This study provides valuable information to find a better treatment for OA.

Host liver-derived extracellular vesicles deliver miR-142a-3p induces neutrophil extracellular traps via targeting WASL to block the development of Schistosoma japonicum.

Schistosomiasis is an important neglected tropical disease. Interactions between the host immune system and schistosomes are complex. Neutrophils contribute to clearance of large pathogens primarily by releasing neutrophil extracellular traps (NETs). However, the functional role of NETs in clearing schistosomes remains unclear. Herein, we report that extracellular vesicles (EVs) derived from the liver of Schistosoma japonicum-infected mice (IL-EVs) induce NET release by delivering miR-142a-3p to target WASL and block the development of S. japonicum. WASL knockout accelerated the formation of NETs that blocked further development of S. japonicum. miR-142a-3p and NETs upregulated the expression of CCL2, which recruits macrophages that block S. japonicum development. However, S. japonicum inhibited NET formation in wild-type mice by upregulating host interleukin-10 (IL-10) expression. In contrast, in WASL knockout mice, IL-10 expression was downregulated, and S. japonicum-mediated inhibition of NET formation was significantly reduced. IL-EV-mediated induction of NET formation is thus an anti-schistosome response that can be counteracted by S. japonicum. These findings suggest that IL-EV-mediated induction of NET formation plays a key role in schistosome infection and that WASL is a potential therapeutic target in schistosomiasis and other infectious diseases.

LncRNA MALAT1 improves cerebral ischemia-reperfusion injury and cognitive dysfunction by regulating miR-142-3p/SIRT1 axis.

PURPOSE: To investigate the regulation and related mechanisms of MALAT1 in cerebral ischemia- reperfusion (CI/R) injury. MATERIALS AND METHODS: 72 mice were divided into sham group (n=24), MCAO group (n=24), MCAO+pcDNA-NC group (n=12) and MCAO+MALAT1 group (n=12). At 12 h, 24 h and 48 h after reperfusion, 6 mice were randomly selected from the sham group and the MCAO group to detect the expression of MALAT1, miR-142-3p and SIRT1 in brain tissue. All mice were scored for neurobehavioral after 48 h of reperfusion. After the completion of the scoring, 6 mice were randomly selected from each group and brain tissue was obtained for TTC analysis. The remaining mice of each group were kept on the Morris water maze test after 3 days of feeding. TTC staining and cerebral infarct volume determination. The infarct size of each brain slice was calculated using Image J image analysis software. OGD/R model PC12 cells were prepared according to simulating CI/R injury in vitro. MALAT1 was cloned into the pcDNA3.1 to construct a MALAT1 overexpression vector with the empty vector NC as a control. Plasmid or oligonuceotides were transfected into PC12 cells. The content of TNF-α, IL-1ß, IL-6, the content of reactive oxygen species (ROS), malondialdehyde (MDA) in brain tissue was detected. The activity of superoxide dismutase (SOD), catalase (CAT) activity was measured. RESULTS: MALAT1 was down-regulated in a time-dependent manner in CI/R-damaged mouse cerebral cortex and OGD/R-induced PC12 cells, accompanied by an increase in the expression of miR-142-3p and a decrease in sirtuin 1 (SIRT1) expression. Overexpression of MALAT1 inhibited OGD/R-induced cell necrosis and apoptosis and promoted cell proliferation. Overexpression of MALAT1 reduced the levels of TNF-α, IL-6, IL-1ß, ROS and MDA and increased the activities of SOD and CAT in OGD/R-injured PC12 cells. MALAT1 negatively regulated the expression of miR-142-3p, and SIRT1 was a target gene of miR-142-3p. The expression of SIRT1 induced by MALAT1 overexpression was obviously abolished by the introduction of miR-142-3p mimic. MALAT1 overexpression can exert its role by regulating the miR-142-3p/SIRT1 axis. Besides, overexpression of MALAT1 improved cerebral infarction, neurological impairment and cognitive dysfunction in CI/R mice. CONCLUSION: MALAT1 mediates SIRT1 expression by acting as a ceRNA of miR-142-3p to improve CI/R injury.Abbreviations: CAT: catalase; CI/R: cerebral ischemia-reperfusion; IL-1ß: interleukin-1ß; IL-6: interleukin-6; lncRNA: long-chain non-coding RNA; MALAT1: metastasis-associated lung adenocarcinoma transcript1; MCAO: middle cerebral artery occlusion; MDA: malondialdehyde; OGD/R: oxygen-glucose deprivation and reoxygenation; ROS: reactive oxygen species; SIRT1: sirtuin 1; SOD: superoxide dismutase; TNF-α: tumour necrosis factor-alpha.

Tissue and Circulating MicroRNAs 378 and 142 as Biomarkers of Obesity and Its Treatment Response.

Promising approaches to the treatment of obesity include increasing energy expenditure and slowing down fibrogenesis of adipose tissue. The neurotransmitter reuptake inhibitor sibutramine affects appetite and activates lipolysis in a catecholaminergic way. MicroRNAs (miRs) are considered as biomarkers of molecular genetic mechanisms underlying various processes. The profile of a number of miRs is altered in obesity, both in the circulation and in adipose tissue. The aim of this study was to assess the expression levels of miRs (hsa-miR-378a-3p, hsa-miR-142-3p) by real-time polymerase chain reaction in subcutaneous adipose tissue (SAT) and in plasma in patients with different degrees and duration of obesity and during sibutramine therapy. This study included 51 obese patients and 10 healthy subjects with normal weight who formed a control group. The study found that, before treatment, obese patients had no significant difference in the expression level of miR-378 in SAT and plasma compared to the control group, while the expression of miR-142 was significantly decreased in SAT and increased in plasma. A significant elevation in miR-378 expression level was noted in patients with first-degree obesity and duration of less than 10 years, and the decline in miR-142 increased with the duration of obesity. These data indicate a maximal increase in the expression of the adipogenesis inducer miR-378 in the early stages of obesity, a progressive decrease in the expression of the fibrogenesis inhibitor miR-142 in SAT with growth of duration of obesity and the likely presence of antifibrogenic effects of sibutramine realized through miR-142 activation.

Elevated Levels of Circulating lncRNAs LIPCAR and MALAT1 Predict an Unfavorable Outcome in Acute Coronary Syndrome Patients.

Coronary artery disease (CAD) is a leading cause of mortality worldwide. In this study, we aimed to assess the potential of plasma long non-coding RNAs (lncRNAs) LIPCAR and MALAT1 and microRNAs (miRNAs) miR-142-3p and miR-155-5p to discriminate unstable CAD patients from stable ones. 23 stable angina (SA), 21 unstable angina (UA), and 50 ST-segment elevation myocardial infarction (STEMI) patients were enrolled; their plasma was collected. ncRNA plasma levels were evaluated using RT-qPCR. All measured ncRNA levels were significantly increased in UA patients' plasma compared to SA patients' plasma and in STEMI-with major adverse cardiovascular event (MACE) patients' plasma vs. STEMI-without MACE patients' plasma. ROC analysis showed that increased levels of LIPCAR and MALAT1 were associated with UA, and the prognostic model improved with the addition of miR-155-5p levels. The assessed lncRNAs discriminated between hyperglycemic (HG) and normoglycemic (NG) UA patients, and they were associated with MACE incidence in STEMI patients; this prediction was improved by the addition of miR-142-3p levels to the ROC multivariate model. We propose LIPCAR and MALAT1 as effective diagnostic markers for vulnerable CAD, their association with HG in UA patients, and as robust predictors for unfavorable evolution of STEMI patients.

EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling.

CircBRWD3 is a newly discovered circRNA, and its potential function has not been probed. Here, we aimed to molecularly dissect the role of circBRWD3 in the tumorigenesis and progression of breast cancer (BC). qRT-PCR analysis revealed that circBRWD3 expression was dramatically upregulated in BC tissues, a feature that was positively correlated with the poor prognosis of patients with BC. CircBRWD3 knockdown repressed cell proliferation and metastasis, while promoting cell apoptosis in vitro. Consistently, an in vivo circBRWD3 deficiency model exhibited suppressed tumor metastasis and oncogenesis. On the other hand, circBRWD3 overexpression promoted cancer cell activity and tumorigenesis. Further, mechanistic studies elucidated that circBRWD3 sponged both miR-142-3p and miR-142-5p to modulate RAC1 expression, which subsequently activated the RAC1/PAK1 signaling to facilitate the tumorigenesis and progression of BC. Moreover, we discovered that EIF4A3 facilitated circBRWD3 expression by targeting the upstream of BRWD3 pre-mRNA. In conclusion, our study reveals that circBRWD3 facilitates BC tumorigenesis by regulating the circBRWD3/miR-142-3p_miR-142-5p /RAC1/PAK1 axis. In addition, circBRWD3 expression is positively regulated by an RNA-binding protein, EIFA3. Our results provide valuable scientific data for early diagnosis and therapy for breast cancer patients.