BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Li-Xin Tang,Guo-Hua Chen,Huan Li,Ping He,Yan Zhang,Xue-Wen Xu
Long noncoding RNA (OGFRP1) has been reported to be involved in the progression of non-small cell lung cancer (NSCLC). However, the expression pattern, functions and molecular mechanisms of OGFRP1 in NSCLC remains unclear. In the present study, we found that OGFRP1 expression was significantly up-regulated in both NSCLC tissues and cell lines, and the upregulation of OGFRP1 expression is a powerful predictor of advanced clinical stage, lymph nodes metastasis and poor prognosis for NSCLC patients. Loss-of-function assay indicated that knockdown of OGFRP1 inhibited proliferation, migration and invasion, and induced apoptosis in vitro. Mechanistically, OGFRP1 could directly bind to miR-124-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-124-3p to promote the expression of the target gene LYPD3. Taken together, OGFRP1 contributed to progression of NSCLC at least partly through upregulating LYPD3 expression by sponging miR-124-3p, indicating that OGFRP1 may be a novel prognostic biomarker and therapeutic target in NSCLC.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PSYCHOPHARMACOLOGY
·
2018
·
IF 4.738
Li-Tao Yi,Rong-Hao Mu,Shu-Qi Dong,Shuang-Shuang Wang,Cheng-Fu Li,Di Geng,Qing Liu
Our previous study demonstrated that gypenosides produced antidepressant-like effects in mice exposed to chronic mild stress in a brain-derived neurotrophic factor-dependent manner. However, whether other mechanisms are involved in the antidepressant-like effects of gypenosides is not clear. miR-124 is one of the most abundant microRNAs in the hippocampus, and its dysregulation is related to the pathophysiology of depression. The glucocorticoid receptor is dysfunctional in depression, and it is a direct target of miR-124. Therefore, the present study used corticosterone-induced mice as a model to evaluate the role of miR-124 on the antidepressant-like effects of gypenosides. miR-124 agomir was intracerebrally injected prior to administration of gypenosides and corticosterone injection. Sucrose preference and forced swimming tests were performed 21 days later. Proteins related to glucocorticoid receptors and brain-derived neurotrophic factor-tyrosine receptor kinase B signaling in the hippocampus were evaluated. Our results demonstrated that gypenosides reversed the chronic corticosterone injection-induced decreased sucrose preference and increased immobility time. In contrast, this effect was antagonized by miR-124 injection. In addition, gypenosides increased glucocorticoid receptor and tyrosine receptor kinase B expression in the hippocampus, which activated brain-derived neurotrophic factor signaling. miR-124 also blocked these effects. In conclusion, this study demonstrated that a reduction in miR-124 was required for the antidepressant-like effects of gypenosides induced by chronic corticosterone injection in mice.
研究领域:
药理学
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-20
·
IF 9.429
Wu Longlong,Tian Xuan,Zuo Huaiwen,Zheng Weiping,Li Xiang,Yuan Mengshu,Tian Xiaorong,Song Hongli
Background Steatotic livers tolerate ischemia–reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown.Methods A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos.Results We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis.Conclusion Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts.Graphical Abstract
研究领域:
分子生物学
·
细胞生物学
·
移植学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HUMAN HYPERTENSION
·
2020
·Vol. 35
·期 8
·696-708
·
IF 2.26
Lv Lingchun,Shen Jiayi,Xu Jian,Wu Xiaoyan,Zeng Chunlai,Lin Li,Mao Wei,Wei Tiemin
Through previous literature studies, we found that miR-124-3p may be associated with hypertension. Therefore, we investigated the relationship between miR-124-3p and hypertension in Human Umbilical Vein Endothelial Cells (HUVECs) induced by angiotensin II (AngII). AngII-induced HUVECs model was constructed and the expression of miR-124-3p was detected by qRT-PCR. After transfected cells, apoptosis and ROS production were detected by flow cytometry, caspase-3 kit, and DCFH-DA staining. The target genes of miR-124-3p were predicted and verified by TargrtScan, Luciferase assay, qRT-PCR, and western blot. After silencing Early growth response factor 1 (siEGR1), its effects on apoptosis and ROS production were explored. Finally, the rescue experiments were conducted to explore the mechanism of miR-124-3p to reduce hypertension. MiR-124-3p was underexpressed in the cell model. In Ang II-induced HUVECs, the number of apoptosis increased, the content of caspase-3 was higher, and ROS production increased. However, these effects could be partially inhibited by miR-124-3p mimic. EGR1 was down-regulated by miR-124-3p, and siEGR1 was able to inhibit apoptosis and ROS production of cell model. In the final rescue experiments, miR-124-3p partially reversed the effect of Ang-II on the viability, migration, invasion and apoptosis and ROS production in HUVECs by down-regulating EGR1. MiR-124-3p inhibits Ang II-induced apoptosis and ROS production in HUVECs by down-regulating EGR1.
研究领域:
心血管研究
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR PROBES
·
2019
·
IF 2.511
Danning Lou,Jun Wang,Xiaohang Wang
Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide and a major public health concern that is associated with grave consequences. Systemic complexity and feedback processes among diverse drivers of the depression disorder contribute to the considerable variation in responses to the treatment of depression . Dysfunctional microRNA (miRNA) is involved in MDD. miR-124 is enriched in the brain and may be critical in neuronal differentiation . Previous studies have shown the value of miRNA-124 as a putative therapeutic target and a biomarker for major depression. However, the detailed mechanism of action of miR-124 in depression remains poorly understood. Here, we observed that miR-124 was downregulated in the hippocampus of mice with chronic unpredictable mild stress (CUMS). Restoration of miR-124 expression significantly attenuated depressive-like behavior and inhibited microglial activation induced by CUMS. Mechanistically, miR-124 directly targeted signal transducer and activator of transcription 3 (STAT3) in BV2 cells; in addition, upregulation of miR-124 inhibited the increase of inducible nitric oxide synthetase and proinflammatory cytokines , including IL-6, IL-1β, TNF-α, and MCP-1, in LPS-stimulated BV2 cells. The collective data suggest that dysfunction of miR-124 may be a foundation for the development of depression by promoting microglial activation.
研究领域:
神经科学
·
分子生物学
·
精神病学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers of Medicine
·
2021
·Vol. 15
·期 6
·887-902
·
IF 4.592
Wu Xin,Wang Zongqi,Li Haiying,Xie Xueshun,Wu Jiang,Shen Haitao,Li Xiang,Wang Zhong,Chen Gang
Monocarboxylic acid transporter 1 (MCT1) maintains axonal function by transferring lactic acid from oligodendrocytes to axons. Subarachnoid hemorrhage (SAH) induces white matter injury, but the involvement of MCT1 is unclear. In this study, the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH. At 48 h after SAH, oligodendrocyte MCT1 was significantly reduced, and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function. Motor training after SAH significantly increased the number of ITPR2 + SOX10 + oligodendrocytes and upregulated the level of MCT1, which was positively correlated with the behavioral ability of rats. In addition, miR-29b and miR-124 levels were significantly increased in SAH rats compared with non-SAH rats. Further intervention experiments showed that miR-29b and miR-124 could negatively regulate the level of MCT1. This study confirmed that the loss of MCT1 may be one of the mechanisms of white matter damage after SAH and may be caused by the negative regulation of miR-29b and miR-124. MCT1 may be involved in the neurological improvement of rehabilitation training after SAH.
研究领域:
神经科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Shuo Li,Xiang-Yu Pei,Xin-Yi Liu,Shu-Liang Wang,Wen Xu,Jing-Jing Wang,Zhen Feng,Han Ding,Yin-Feng Zhang,Rui Zhang
MicroRNAs (miRNAs) are small noncoding RNAs of 18–25 bases. miRNAs are also important new biomarkers that can be used for disease diagnosis in the future. Studies have shown that miR-124 levels are significantly elevated during acute myocardial infarction (AMI) and play a key role in the cardiovascular system. A variety of methods have been established to detect myocardial infarction-related miRNAs. However, most require complex miRNA extraction and isolation, and these methods are virtually undetectable when RNA levels are low in the sample. It may lead to biased results. Thus, it is necessary to develop a technique that can detect miRNA without extracting it, which means that intracellular detection is of great significance. Here, we improved the traditional silicon spheres and obtained a biosensor that could effectively capture and detect specific noncoding nucleic acids through the layer-by-layer assembly method. The sensor is protected by hyaluronic acid so it can successfully escape the lysosome into the cell and achieve detection. With the help of a full-featured microplate reader, we determined that the detection limit of the biosensor could reach 1 fM, meeting the needs of intracellular detection. At the same time, we prepared an oxidative stress cardiomyocyte infarction model and successfully captured the overexpressed miR-124 in the infarcted cells to achieve in situ detection. This study could provide a new potential tool to develop miRNAs for sensitive diagnosis in AMI, and the proposed strategy implies its potential for biomedical research.
研究领域:
分子生物学
·
生物医学工程
·
心脏病学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Mingju Shui,Yi Chen,Miao Guo,Guofeng Zhong,Hongyi Li,Yaqin Xiao,Qin Yuan,Beixin Yuan,Xiaoying Liu,Hefeng Zhou,Zhejie Chen,Shengpeng Wang
Ulcerative Colitis (UC) is a chronic intestinal disease with limited treatment options, where current therapies often suffer from inadequate efficacy and substantial side effects. While polyphenol-based nanocarriers show promise for nucleic acid delivery, a systematic screening approach to identify optimal polyphenols for this purpose remains unexplored. Therefore, we conducted a systematic screening of 110 natural polyphenols to develop an efficient miRNA delivery system for UC intervention. Sinapic acid (SA) was identified as the lead candidate and complexed with miR-124 mimics, followed by sequential encapsulation with a poly(amidoamine) (PAMAM) dendrimer and hyaluronic acid (HA) coating to form HPPR NPs. As expected, HPPR mediated efficient intracellular delivery of miR-124, leading to significant downregulation of the expression of IL-6R , CCL-2 , STAT3 , and their downstream genes in a murine model of dextran sulfate sodium (DSS)-induced acute colitis. HPPR also markedly suppressed the production of pro-inflammatory cytokines and facilitated intestinal mucosal regeneration. Moreover, the system effectively modulated gut microbiota homeostasis by enriching beneficial bacteria ( Akkermansia and norank_f__Muribaculaceae ) while simultaneously suppressing pathogenic bacteria ( Escherichia-Shigella and Helicobacter ). Collectively, this study not only establishes a polyphenol-based strategy for optimizing nucleic acid delivery but also presents a promising nanotherapeutic platform for UC treatment.
研究领域:
纳米医学
·
分子生物学
·
胃肠病学
·
药物递送
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2023
·Vol. 11
·期 2
·e730
·
IF 3.2
Min Liu,Shuang Liu,Fajiu Li,Chenghong Li,Shi Chen,Xiaoyan Gao,Xiaojiang Wang
Objective Asthma is a chronic respiratory disease with an increasing incidence every year. microRNAs (miRNAs) have been demonstrated to have implications for asthma. However, limited information is available regarding the effect of miR-124-3p on this disease. Therefore, this study aimed to explore the possible effects of miR-124-3p and S100A4 on inflammation and epithelial–mesenchymal transition (EMT) in asthma using mouse models. Method Ovalbumin was used to induce asthmatic mouse models. Lung injury in mouse models was assessed, and the bronchoalveolar lavage fluid of mice was collected to determine the number of eosinophilic granulocytes and assess inflammation. The expression levels of miR-124-3p, S100A4, E-cadherin, N-cadherin, Snail1, vimentin, and TGF-β1/Smad2 signaling pathway-related proteins were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. In vitro experiments, cells were transfected with miR-124-3p mimics or inhibitors to test the expression of S100A4 by RT-qPCR and western blot analysis, and the mutual binding of miR-124-3p and S100A4 was validated by dual-luciferase reporter gene assay. Results Overexpression of miR-124-3p or inhibition of S100A4 expression attenuated bronchial mucus secretion and collagenous fibers and suppressed inflammatory cell infiltration. Additionally, upon miR-124-3p overexpression or S100A4 suppression, eosinophilic granulocytes were decreased, interleukin-4 (IL-4) and IL-13 expression levels were reduced in the bronchoalveolar lavage fluid, serum total IgE level was reduced, and the TGF-β1/Smad2 signaling pathway was suppressed. Mechanically, a dual-luciferase reporter gene assay verified the binding relationship between miR-124-3p and S100A4. Conclusion miR-124-3p can negatively target S100A4 to attenuate inflammation in asthmatic mouse models by suppressing the EMT process and the TGF-β/smad2 signaling pathway.
研究领域:
免疫学
·
分子生物学
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AFFECTIVE DISORDERS
·
2025
·
IF 4.9
Huiying Xie,Yan Xue,Rui Deng,Liuxiang Chen,Yiyi Wang,Jia Xu,Hao Liu,Xingxing Li,Wei Cui,Jun-Fang Zhang
Background Stress is a significant trigger of depression, and miR-124 has been implicated in stress-induced depression, while the underlying molecular mechanisms remain unclear. Methods We established mouse depression models using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS), and the HT-22 cell models with corticosterone (CORT) and glutamate (Glu). Depression-like behaviors were assessed using the forced swimming test, tail suspension test, and sucrose preference test. Adeno-associated viruses were employed to manipulate miR-124 and ubiquitin-specific protease 14 (USP14) expression. mRNA levels of miR-124 , Usp14 , and Rest were measured by qRT-PCR, the interaction between miR-124 and Usp14 mRNA was assessed by luciferase reporter assays, protein expression and interaction of USP14 and repressor element 1 silencing transcription factor (REST) were detected by western blotting, ubiquitination assay and co-immunoprecipitation. Immunofluorescence visualized altered REST expression in hippocampal neurons. Results CRS and CUMS robustly increased miR-124 levels in the hippocampus, while decreasing the USP14 and REST expression. Similar expression changes were seen in CORT- and Glu-treated HT-22 cells. Mice with miR-124 overexpression but not inhibition in the hippocampus exhibited notable depression-like behavior. Mechanistically, miR-124 directly targeted USP14, reduced USP14 binding to REST, thereby increasing REST ubiquitination and degradation. Inhibition of miR-124 produced antidepressant-like effects and restored the expression and interaction of USP14 and REST in the CRS and CUMS mice. Furthermore, overexpression of USP14 alleviated depression-like behaviors and low REST levels. Conclusion Hippocampal miR-124 mediates depression-like behavior under chronic stress via regulating the USP14/REST signaling pathway, highlighting its potential as a therapeutic target.
研究领域:
神经生物学
·
分子精神病学
·
信号转导
·
表观遗传学
·
应激生理学
·
神经药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）