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  1. Article ; Online: Regulation of intestinal flora in patients with chronic atrophic gastritis by modified Chai Shao Liu Jun Zi decoction based on 16S rRNA sequencing.

    Xing, Chongyi / Liu, Yuna / Wang, Shaohua / Zhang, Jing / Liu, Gang / Li, Na / Leng, Yan / Ying, Dashi / Xu, Chunfeng

    Medicine

    2024  Volume 103, Issue 6, Page(s) e37053

    Abstract: Chai Shao Liu Jun Zi decoction (CSLJZD) is an effective Chinese medicine for the treatment ...

    Abstract Chai Shao Liu Jun Zi decoction (CSLJZD) is an effective Chinese medicine for the treatment of chronic atrophic gastritis (CAG). However, the effect of CSLJZD on the intestinal flora of patients with CAG remains unclear. We used 16S rRNA gene sequencing to investigate the regulatory effects of CSLJZD on intestinal microflora in patients with CAG. Eight patients with CAG were randomly selected as the model group and 8 healthy medical examiners as the control group; the treatment group comprised patients with CAG after CSLJZD treatment. High-throughput sequencing and bioinformatics analysis of the V3V4 region of the 16S rRNA gene of intestinal bacteria obtained from the intestinal isolates of fecal specimens from all participants were performed separately. A rarefaction curve, species accumulation curve, Chao1 index, and ACE index were calculated to assess the alpha diversity. Principal component analysis (PCA), non-metric multi-dimensional scaling, and the unweighted pair group method with arithmetic mean were used to examine beta diversity. The LEfSe method was used to identify the differentially expressed bacteria. Differential function analysis was performed using PCA based on KEGG function prediction. Rarefaction and species accumulation curves showed that the sequencing data were reasonable. The Chao1 and ACE indices were significantly increased in patients with CAG compared with those in the healthy group. Following CSLJZD and vitacoenzyme treatment, Chao1 and ACE indices decreased. The PCA, non-metric multi-dimensional scaling, and unweighted pair group method with arithmetic mean results showed that the CAG group was distinct from the healthy and treatment groups. The LEfSe results showed that the abundances of the genus Bilophila, family Desulfovibrionaceae, order Desulfovibrionales and genus Faecalibacterium were significantly higher in the healthy group. The abundance of genus Klebsiella, order Deltaproteobacteria, genus Gemmiger, and other genera was significantly higher in the treatment group. Treatment with CSLJZD had a therapeutic effect on the intestinal flora of patients with CAG.
    MeSH term(s) Humans ; Gastritis, Atrophic/drug therapy ; RNA, Ribosomal, 16S/genetics ; Gastrointestinal Microbiome/genetics ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Autoimmune Diseases/drug therapy
    Chemical Substances RNA, Ribosomal, 16S ; Drugs, Chinese Herbal
    Language English
    Publishing date 2024-02-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80184-7
    ISSN 1536-5964 ; 0025-7974
    ISSN (online) 1536-5964
    ISSN 0025-7974
    DOI 10.1097/MD.0000000000037053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SENP3-mediated deSUMOylation of c-Jun facilitates microglia-induced neuroinflammation after cerebral ischemia and reperfusion injury.

    Xia, Qian / Mao, Meng / Zhan, Gaofeng / Luo, Zhenzhao / Zhao, Yin / Li, Xing

    iScience

    2023  Volume 26, Issue 6, Page(s) 106953

    Abstract: ... in microglial cells. Mechanistically, SENP3 can bind and then mediated the deSUMOylation of c-Jun ... by activating the MAPK/AP-1 signaling pathway via mediating the deSUMOylation of c-Jun. Interventions of SENP3 ... expression or its interaction with c-Jun would be a new and promising therapeutic strategy for ischemic ...

    Abstract Recent evidences have implicated that SENP3 is a deSUMOylase which possesses neuronal damage effects in cerebral ischemia. However, its role in microglia remains poorly understood. Here, we found that SENP3 was upregulated in the peri-infarct areas of mice following ischemic stroke. Furthermore, knockdown of SENP3 significantly inhibits the expression of proinflammatory cytokines and chemokines in microglial cells. Mechanistically, SENP3 can bind and then mediated the deSUMOylation of c-Jun, which activated its transcriptional activity, ultimately followed by the activation of MAPK/AP-1 signaling pathway. In addition, microglia-specific SENP3 knockdown alleviated ischemia-induced neuronal damage, and markedly diminished infract volume, ameliorated sensorimotor and cognitive function in animals subjected to ischemic stroke. These results indicated SENP3 functions as a novel regulator of microglia-induced neuroinflammation by activating the MAPK/AP-1 signaling pathway via mediating the deSUMOylation of c-Jun. Interventions of SENP3 expression or its interaction with c-Jun would be a new and promising therapeutic strategy for ischemic stroke.
    Language English
    Publishing date 2023-05-25
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106953
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer.

    Miao, Ran / Dai, Cong-Cong / Mei, Lin / Xu, Jun / Sun, Shan-Wen / Xing, Yun-Long / Wu, Li-Sheng / Wang, Ming-Hai / Wei, Ji-Fu

    Journal of cellular physiology

    2020  Volume 235, Issue 10, Page(s) 7420–7432

    Abstract: ... targeted gene, c-Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower ... regulating gene as c-Jun by mRNAs high-throughput sequencing and RIP assay. By luciferase assay, we verified ... that KIAA1429 regulated the expression of c-Jun in an m6A-independent manner. Finally, the overexpression of c ...

    Abstract N6-methyladenosine (m6A) modification regulatory proteins are involved in the development of many types of cancer. KIAA1429 serves as a scaffold in bridging the catalytic core components of the m6A methyltransferase complex. The role of KIAA1429 in gastric cancer and its related mechanism has not been reported upon. The expression of KIAA1429 was detected in human gastric cancer tissues and cell lines by quantitative real-time polymerase chain reaction and western blot. The effects of KIAA1429 on gastric cancer proliferation were evaluated by cell counting kit assays, colony formation assays, flow cytometry assay, and in vivo experiments with nude mice. And messenger RNA (mRNA) high-throughput sequencing, RNA immunoprecipitation assay (RIP), luciferase assay, and a rescue experiment were used to identify the relationship between KIAA1429 and its specific targeted gene, c-Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower in adjacent tissues. The upregulated KIAA1429 promoted proliferation and downregulated KIAA1429 was proved to inhibit proliferation of gastric cancer in vitro and in vivo. Then, we identified the potential KIAA1429 regulating gene as c-Jun by mRNAs high-throughput sequencing and RIP assay. By luciferase assay, we verified that KIAA1429 regulated the expression of c-Jun in an m6A-independent manner. Finally, the overexpression of c-Jun rescued the inhibition of proliferation caused by KIAA1429 knockdown in gastric cancer cells. KIAA1429 could act as an oncogene in gastric cancer by stabilizing c-Jun mRNA in an m6A-independent manner. This highlights the functional role for KIAA1429 as a potential prognostic biomarker and therapeutic target in gastric cancer.
    MeSH term(s) Animals ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Down-Regulation/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Prognosis ; Proto-Oncogene Proteins c-jun/genetics ; RNA, Messenger/genetics ; RNA-Binding Proteins/genetics ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Up-Regulation/genetics ; Xenograft Model Antitumor Assays/methods
    Chemical Substances Biomarkers, Tumor ; Proto-Oncogene Proteins c-jun ; RNA, Messenger ; RNA-Binding Proteins ; VIRMA protein, human
    Language English
    Publishing date 2020-02-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.29645
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Impinging Flow Induces Expression of Monocyte Chemoattractant Protein-1 in Endothelial Cells Through Activation of the c-Jun N-terminal Kinase/c-Jun/p38/c-Fos Pathway.

    Zhu, Huaxin / Hao, Zheng / Xing, Zelong / Tan, Jiacong / Zhao, Yeyu / Li, Meihua

    World neurosurgery

    2022  Volume 164, Page(s) e681–e693

    Abstract: ... of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, activator protein-1, and MCP-1 were detected ... the phosphorylation levels of ERK, JNK, and p38, as well as the protein levels of MCP-1, c-Jun, and c-Fos, increased ... factors are regulated through the JNK/c-Jun/p38/c-Fos pathway and participate in EC inflammation. ...

    Abstract Objective: Monocyte chemoattractant protein-1 (MCP-1) is an important regulator of the formation and development of intracranial aneurysms. This study explored the molecular mechanisms underlying the induction of MCP-1 and related inflammatory factors in human umbilical vein endothelial cells (HUVECs) under hemodynamic conditions.
    Methods: A modified T chamber was used to simulate fluid flow at the bifurcation of the artery and wall shear stress on HUVECs in vitro. Changes in HUVECs were analyzed in response to impinging flow. And HUVECs without impinging flow were used as the control group. Protein expression levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, activator protein-1, and MCP-1 were detected by Western blot, and the messenger RNA expression levels of MCP-1, interleukin (IL)-1β, and IL-6 were determined by quantitative reverse transcription polymerase chain reaction.
    Results: Under impinging flow, the phosphorylation levels of ERK, JNK, and p38, as well as the protein levels of MCP-1, c-Jun, and c-Fos, increased. The messenger RNA expression of MCP-1, IL-1β, and IL-6 also increased in HUVECs. Pretreatment of the HUVECs with inhibitors of JNK and p38 significantly attenuated the increased expression of MCP-1, IL-1β, and IL-6, while ERK inhibitors had no obvious effect.
    Conclusions: Under impinging flow, MCP-1 and inflammatory factors are regulated through the JNK/c-Jun/p38/c-Fos pathway and participate in EC inflammation.
    MeSH term(s) Cells, Cultured ; Chemokine CCL2/genetics ; Chemokine CCL2/metabolism ; Extracellular Signal-Regulated MAP Kinases ; Human Umbilical Vein Endothelial Cells ; Humans ; Interleukin-6/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; RNA, Messenger/metabolism
    Chemical Substances Chemokine CCL2 ; Interleukin-6 ; RNA, Messenger ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2022-05-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2534351-8
    ISSN 1878-8769 ; 1878-8750
    ISSN (online) 1878-8769
    ISSN 1878-8750
    DOI 10.1016/j.wneu.2022.05.032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: MicroRNA-139-5p upregulation is associated with diabetic endothelial cell dysfunction by targeting c-jun.

    Luo, Yu-Fang / Wan, Xin-Xing / Zhao, Li-Ling / Guo, Zi / Shen, Rui-Ting / Zeng, Ping-Yu / Wang, Ling-Hao / Yuan, Jing-Jing / Yang, Wen-Jun / Yue, Chun / Mo, Zhao-Hui

    Aging

    2020  Volume 13, Issue 1, Page(s) 1186–1211

    Abstract: ... proliferation, and down-regulated expression of c-jun, vascular endothelial growth factor (VEGF), and ... of ECFCs by targeting c-jun-VEGF/PDGF-B pathway. ...

    Abstract Dysfunction of endothelial cells (ECs) and their progenitor cells is an important feature of diabetic vascular disease. MicroRNA (miR)-139-5p is involved in inhibiting the metastasis and progression of diverse malignancies. However, the role of miR-139-5p in ECs still remains unclarified. Here we demonstrated that miR-139-5p expression was elevated in endothelial colony-forming cells (ECFCs) isolated from patients with diabetes, ECs derived from the aorta of diabetic rodents, and human umbilical vein endothelial cells (HUVECs) cultured in high glucose media. MiR-139-5p mimics inhibited tube formation, migration, proliferation, and down-regulated expression of c-jun, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF)-B, in ECFCs and HUVECs, respectively; moreover, miR-139-5p inhibitors reversed the tendency. Further, gain- and-loss function experiments and ChIP assay indicated that miR-139-5p regulate functions of ECFCs by targeting c-jun-VEGF/PDGF-B pathway.
    MeSH term(s) Adult ; Animals ; Aorta/cytology ; Case-Control Studies ; Diabetes Mellitus, Type 2/metabolism ; Diabetic Angiopathies/metabolism ; Endothelial Cells/metabolism ; Female ; Human Umbilical Vein Endothelial Cells ; Humans ; Male ; Mice ; MicroRNAs/metabolism ; Middle Aged ; Neovascularization, Physiologic/physiology ; Proto-Oncogene Proteins c-jun/metabolism ; Proto-Oncogene Proteins c-sis/metabolism ; Rats ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances MIRN139 microRNA, human ; MIRN139 microRNA, mouse ; MIRN139 microRNA, rat ; MicroRNAs ; Proto-Oncogene Proteins c-jun ; Proto-Oncogene Proteins c-sis ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2020-12-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.202257
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: FK866 attenuates sepsis-induced acute lung injury through c-jun-N-terminal kinase (JNK)-dependent autophagy.

    Zheng, Qiang / Wang, Yu-Chang / Liu, Qin-Xin / Dong, Xi-Jie / Xie, Zhen-Xing / Liu, Xing-Hua / Gao, Wei / Bai, Xiang-Jun / Li, Zhan-Fei

    Life sciences

    2020  Volume 250, Page(s) 117551

    Abstract: Aims: Increasing evidence indicates that FK866, a specific noncompetitive nicotinamide phosphoribosyl transferase inhibitor, exhibits a protective effect on acute lung injury (ALI). Autophagy plays a pivotal role in sepsis-induced ALI. However, the ... ...

    Abstract Aims: Increasing evidence indicates that FK866, a specific noncompetitive nicotinamide phosphoribosyl transferase inhibitor, exhibits a protective effect on acute lung injury (ALI). Autophagy plays a pivotal role in sepsis-induced ALI. However, the contribution of autophagy and the underlying mechanism by which FK866-confered lung protection remains elusive. Herein, we aimed to study whether FK866 could alleviate sepsis-induced ALI via the JNK-dependent autophagy.
    Main methods: Male C57BL/6 mice were subjected to cecal ligation and puncture (CLP) to establish the polymicrobial sepsis mice model, and treated with FK866 (10 mg/kg) at 24, 12 and 0.5 h before the CLP procedure. The lung protective effects were measured by lung histopathology, tissue edema, vascular leakage, inflammation infiltration, autophagy-related protein expression and JNK activity. A549 cells were stimulated with LPS (1000 ng/ml) to generate the ALI cell model, and pretreated with FK866 or SP600125 for 30 min to measure the autophagy-related protein expression and JNK activity.
    Key findings: Our results demonstrated that FK866 reduced lung injury score, tissue edema, vascular leakage, and inflammatory infiltration, and upregulated autophagy. The protective effect of autophagy conferred by FK866 on ALI was further clarified by using 3-methyladenine (3MA) and rapamycin. Additionally, the activity of JNK was suppressed by FK866, and inhibition of JNK promoted autophagy and showed a benefit effect.
    Significance: Our study indicates that FK866 protects against sepsis-induced ALI by induction of JNK-dependent autophagy. This may provide new insights into the functional mechanism of NAMPT inhibition in sepsis-induced ALI.
    MeSH term(s) A549 Cells ; Acrylamides/therapeutic use ; Acute Lung Injury/complications ; Acute Lung Injury/drug therapy ; Animals ; Autophagy ; Bronchoalveolar Lavage Fluid ; Capillary Permeability ; Disease Models, Animal ; Humans ; Lung/drug effects ; MAP Kinase Kinase 4/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Piperidines/therapeutic use ; Sepsis/complications ; Sepsis/drug therapy ; Signal Transduction ; Up-Regulation
    Chemical Substances Acrylamides ; N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide ; Piperidines ; MAP Kinase Kinase 4 (EC 2.7.12.2)
    Language English
    Publishing date 2020-03-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2020.117551
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Astragaloside IV ameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway.

    Xiaomei, Y E / Xiaowei, Xing / Kangrui, Yuan / Dongming, Wang / Dudu, W U / Zhi, Chen / Zhiqiang, Y U

    Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan

    2023  Volume 43, Issue 1, Page(s) 60–67

    Abstract: ... that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal ...

    Abstract Objective: To investigate the effects and elucidate the mechanism of Astragaloside IV (AS-IV) for insulin resistance (IR) and type 2 diabet es mellitus (T2DM).
    Methods: CCK8 kit was used to detect cell viability, glucose detection kit was used to detect the concentration of glucose in cell supernatant, reactive oxygen species (ROS) detection kit and Western blot were used to explore the mechanism of Astragaloside IV (AS-IV) in improving IR. A diabetic rat model was also established by feeding high sugar and fat diet and streptozotocin (STZ) injection. After treatment with AS-IV, rosiglitazone (ROZ), or normal saline, the fasting blood glucose (FBG), C peptide (C-P), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and the glucose tolerance were assessed.
    Results: AS-IV could effectively reduce the content of ROS and increase the glucose uptake in high insulin-treated IR-type HepG2 cells. The results of molecular mechanisms indicated that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal kinase (JNK) downstream protein expression. Additionally, AS-IV could significantly reduce the levels of FBG, TNF-α, IL-6 and the glucose tolerance in diabetic rats ( < 0.05 or < 0.01). The high and medium dose groups of AS-IV could significantly increase the C-P levels in diabetic rats ( < 0.05 or < 0.01).
    Conclusions: Our results indicated that AS-IV improve liver IR through the JNK pathway and ROS, which meant a new molecular target for the treatment of diabetes. The AS-IV also helped to prevent and improved the insulin resistance of rats.
    MeSH term(s) Rats ; Animals ; Humans ; Insulin ; Insulin Resistance/physiology ; Reactive Oxygen Species/metabolism ; JNK Mitogen-Activated Protein Kinases ; Hep G2 Cells ; Diabetes Mellitus, Experimental/drug therapy ; Interleukin-6 ; Tumor Necrosis Factor-alpha/genetics ; Glucose/metabolism
    Chemical Substances Insulin ; Reactive Oxygen Species ; astragaloside A (3A592W8XKE) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-02-21
    Publishing country China
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603186-9
    ISSN 2589-451X ; 0254-6272 ; 0255-2922
    ISSN (online) 2589-451X ; 0254-6272
    ISSN 0255-2922
    DOI 10.19852/j.cnki.jtcm.2023.01.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Sporothrix schenckii regulates macrophage inflammatory responses via the c-JUN-induced Dab2 transcription.

    Zhao, Shengnan / Qi, Rui-Qun / Gao, Xing-Hua / Chen, Hong-Duo

    Experimental dermatology

    2022  Volume 31, Issue 9, Page(s) 1330–1340

    Abstract: ... JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c-JUN ... We also identified c-JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and ... with an upregulation of c-JUN and inhibition of JNK activity, which were in accord with findings from in vitro ...

    Abstract Macrophages, which serve as a bridge between innate and adaptive immunity, play an important role in sporotrichosis. Sporothrix schenckii infections can produce immune responses such as macrophage polarization and inflammatory factor secretion. In the early stages of inflammation, the expression of DAB2 in macrophages is increased, which controls the secretion of inflammatory factors and affects the polarization of macrophages. However, the expressions and mechanisms of DAB2 in sporotrichosis are not clear. In this study, we examined the expression of DAB2 and its regulation of inflammatory factors under conditions of Sporothrix schenckii infection. Our results indicated that the Sporothrix schenckii infection increased the expression of DAB2 and revealed a mixed M1/M2-like type of gene expression in BMDMs with the inhibited Il-6, Il1-β and Arg-1 and induced Tnf-α, Il-10 and Mgl-1. The deficiency of Dab2 gene suspended the changes of cytokines. In addition, JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c-JUN. We also identified c-JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and luciferase reporter assays. In an in vivo mouse model, sporotrichosis-induced skin lesions were accompanied with an upregulation of c-JUN and inhibition of JNK activity, which were in accord with findings from in vitro experiments. Taken together, these findings indicate that in the early stages of Sporothrix schenckii infection there is a promotion of DAB2 expression through the JNK/c-JUN pathway, effects that can then control the expression of inflammatory factors.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Apoptosis Regulatory Proteins/metabolism ; Apoptosis Regulatory Proteins/pharmacology ; Macrophages/metabolism ; Mice ; Sporothrix/metabolism ; Sporotrichosis/pathology ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; Dab2 protein, mouse ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2022-05-03
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1130936-2
    ISSN 1600-0625 ; 0906-6705
    ISSN (online) 1600-0625
    ISSN 0906-6705
    DOI 10.1111/exd.14580
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Fibronectin 1 derived from tumor-associated macrophages and fibroblasts promotes metastasis through the JUN pathway in hepatocellular carcinoma.

    Zhang, Liwei / Zhang, Cong / Xing, Zhengwei / Lou, Chunyang / Fang, Jianbang / Wang, Zhiwei / Li, Mingxing / He, Hao / Bai, Hualong

    International immunopharmacology

    2022  Volume 113, Issue Pt A, Page(s) 109420

    Abstract: ... investigated by post-Pan-cancer analysis.: Results: JUN and its regulatory network play a key role in HCC ... communication analysis showed that macrophage and fibroblast-derived FN1 could increase JUN by TNFRSF11B/SMAD3 ... Multiomics analysis showed that KIF13A was a key downstream gene of JUN, which was involved in the activation ...

    Abstract Objective: Intercellular communication in the tumor microenvironment is a potential regulator of metastasis. To explore the specific mechanism, we performed a multi-omics analysis of hepatocellular carcinoma.
    Materials and methods: Multiple omics data including scRNA-seq, ATAC-seq, RNA-seq, and methylation data were obtained from GEO and TCGA databases. SCENIC was used to identify key transcription factors and their Regulatory networks. ScMLnet was used to explore the mechanism of intercellular communication in the microenvironment. Multiple omics studies based on RNA-seq, ATAC-seq, and methylation data were used to explore downstream mechanisms of key transcription factors. Based on the analysis of cell differentiation trajectory and transcription subtypes, the regulation of cell communication on tumor subtypes was studied, and possible therapeutic compounds were explored. The universality of this mechanism was investigated by post-Pan-cancer analysis.
    Results: JUN and its regulatory network play a key role in HCC, which was mainly positively correlated with tumor-associated macrophages and fibroblasts. Intercellular communication analysis showed that macrophage and fibroblast-derived FN1 could increase JUN by TNFRSF11B/SMAD3. Multiomics analysis showed that KIF13A was a key downstream gene of JUN, which was involved in the activation of the hippo pathway. Analysis of cell differentiation trajectory, transcriptome subtypes, and neural network modeling showed that intercellular communication in the microenvironment can regulate the transcriptome characterization of HCC. Pan-cancer analysis indicates that this mechanism may be universal.
    Conclusion: FN1 derived from tumor-associated macrophages and fibroblasts promotes metastasis and alters transcriptome subtypes through the JUN-Hippo signaling pathway in HCC, which may be universal in cancers.
    MeSH term(s) Humans ; Tumor-Associated Macrophages ; Carcinoma, Hepatocellular/genetics ; Fibronectins ; Liver Neoplasms/genetics ; Fibroblasts ; Tumor Microenvironment ; Kinesins
    Chemical Substances Fibronectins ; KIF13A protein, human ; Kinesins (EC 3.6.4.4)
    Language English
    Publishing date 2022-11-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2022.109420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The transcription factor JUN is a major regulator of quiescent pancreatic stellate cell maintenance.

    Lin, Hao / Ye, Zheng / Xu, Rong / Li, Xing-Er / Sun, Bo

    Gene

    2022  Volume 851, Page(s) 147000

    Abstract: ... In this study, we identified JUN, a key transcription factor that maintains the quiescent state of PSCs ... and demonstrated that the expression and activity of JUN is a major regulator of the quiescent state ...

    Abstract Pancreatic stellate cell (PSC) activation is a major cause of chronic pancreatitis and pancreatic cancer, yet the mechanisms by which PSCs switch from quiescent to activated state are poorly studied. In this study, we identified JUN, a key transcription factor that maintains the quiescent state of PSCs, by integrating single-cell sequencing data from multiple pancreatic tissues and using WGCNA and SCENIC algorithms, and demonstrated that the expression and activity of JUN is a major regulator of the quiescent state of PSCs through cellular experiments and multiple pancreatic-related disease bulk RNAseq data. This study explores the main mechanism of PSC activation and provides a theoretical basis for the treatment of multiple pancreatic injury-related diseases caused by PSCs.
    MeSH term(s) Humans ; Pancreatic Stellate Cells/metabolism ; Transcription Factors/metabolism ; Pancreatic Neoplasms/genetics ; Pancreatitis, Chronic/metabolism ; Pancreas/metabolism ; Cells, Cultured
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2022-10-22
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2022.147000
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