检索结果-内蒙古大学图书馆

circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing txnip expression

MOLECULAR THERAPY-NUCLEIC ACIDS 2021年 23卷 355-368页

作者： Liang, Yingkuan Wang, Hui Chen, Bing Mao, Qixing Xia, Wenjie Zhang, Te Song, Xuming Zhang, Zeyu Xu, Lin Dong, Gaochao Jiang, Feng Nanjing Med Univ Affiliated Canc Hosp Baiziting 42 Nanjing 210009 Peoples R China Jiangsu Canc Hosp Jiangsu Inst Canc Res Dept Thorac Surg Nanjing 210029 Peoples R China Canc Inst Jiangsu Prov Jiangsu Key Lab Mol & Translat Canc Res Nanjing Peoples R China Suchow Univ Dept Thorac Surg Affiliated Hosp 1 Suzhou Peoples R China

Aberrant expression of circular RNAs (circRNAs) is involved in cancer progression through interaction with RNA-binding proteins (RBPs). Herein, we screened circRNA expression of A549 cells in circBase and the crosslinking immunoprecipitation (CLIP) data of human antigen R (HuR), an extensively studied RBP, and identified a circRNA, circ-defective in cullin neddylation 1 domain containing 4 (circDCUN1D4), originating from the DCUN1D4 gene transcript. circDCUN1D4 is downregulated in tumor samples under the mediation of DExH-box helicase 9 (DHX9), which inhibits the formation of circRNA by binding inverted repeat Alus (IRAlus) in flanking sequences. circDCUN1D4 depletion promoted invasion in vitro and metastasis in vivo. Importantly, the interaction between circDCUN1D4 and HuR increased the transportation of HuR to the cytoplasm. circDCUN1D4 acts as a scaffold to facilitate the interaction between the HuR protein and thioredoxin-interacting protein (txnip) mRNA, which enhances the stability of the txnip mRNA. Additionally, circDCUN1D4 directly interacts with txnip mRNA through base complementation, indicating the formation of the circDCUN1D4/HuR/txnip RNA-protein ternary complex. Furthermore, circDCUN1D4 suppressed metastasis and glycolysis of lung cancer cells in a txnip-dependent manner. Clinically, the downregulated expression of circDCUN1D4 was more prevalent in lymph node metastatic tissues and served as an independent risk factor for the overall survival of lung adenocarcinoma (LUAD) patients. These findings demonstrated that a novel circRNA, circDCUN1D4, is involved in the metastasis and glycolysis of LUAD.

关键词： circDCUN1D4 txnip glycolysis LUAD HuR circular RNA circRNA metastasis DCUN1D4 RNA binding protein

来源：评论

学校读者我要写书评

暂无评论

Potential of Forsythoside I as a therapeutic approach for acute lung injury: Involvement of txnip/NLRP3 inflammasome

引用

MOLECULAR IMMUNOLOGY 2021年 134卷 192-201页

作者： Liang, Hongwen Liu, Kai Zhuang, Zhe Sun, Hong Sun, Bo Jiao, Minna Cai, Yeqian Cai, Guofeng Heilongjiang Univ Chinese Med Affiliated Hosp 2 Dept Crit Care Med Harbin 150000 Heilongjiang Peoples R China Heilongjiang Univ Chinese Med Affiliated Hosp 2 Dept Internal Med 411 Guogeli St Harbin 150000 Heilongjiang Peoples R China Heilongjiang Univ Chinese Med Affiliated Hosp 2 Dept Ophthalmol Harbin 150000 Heilongjiang Peoples R China Heilongjiang Univ Chinese Med Affiliated Hosp 2 Dept Tuina Massage Harbin 150000 Heilongjiang Peoples R China

Objective: To explore the role of Forsythoside I (FI) in acute lung injury (ALI) mouse and its underling mechanism. Methods: The cell models of ALI are constructed by LPS induction. After pretreatment with different concentrations of FI, the lung injury is assessed by pathological changes of lung tissues and cell apoptosis. The cell viability, levels of pro-inflammatory cytokines, and the activation of txnip/NLRP3 pathway are inspected to investigate whether the effect of FI on inflammatory response is exerted by regulating the txnip/NLRP3 pathway. Results: LPS induces inflammatory cell infiltration, tissue necrosis and pulmonary interstitial edema of mouse tissues, and LPS increases the protein concentration and levels of pro-inflammatory factors in mouse BALF. Additionally, enhanced cell apoptotic level, increased W/D ratio and MPO activity, as well as suppressed SOD activity are observed in LPS-induced mouse models. Those inflammation response, oxidative stress and lung injury can be attenuated by FI (12.5 mg/kg, 25 mg/kg, 50 mg/kg) in a dose-dependent manner. Meanwhile, both in vitro and in vivo studies reveal that FI can lead to suppressed txnip expression and inactivated NLRP3 inflammasomes. txnip is an upstream target of NLRP3, and FI mitigates ALI by decreasing txnip to block NLRP3 inflammasomes. Conclusion: FI protects against ALI through the mediation of txnip/NLRP3 inflammasome axis and therefore has a certain potential for ALI treatment.

关键词： Forsythoside I Acute lung injury txnip NLRP3 inflammasome

来源：评论

学校读者我要写书评

暂无评论

Integrated multiomic data analysis reveals the clinical significance of txnip and contributing to immune microenvironment in triple negative breast cancer

引用

TRANSLATIONAL ONCOLOGY 2024年 39卷 101808-101808页

作者： Gong, Han Zhang, Peihe Hu, Xingming Zhang, Bin Hunan Canc Hosp Dept Thorac Radiat Oncol 1 Changsha 4100013 Peoples R China Cent South Univ Affiliated Canc Hosp Xiangya Sch Med Changsha 4100013 Peoples R China Cent South Univ Mol Biol Res Ctr Changsha Hunan Peoples R China Cent South Univ Sch Life Sci Ctr Med Genet Changsha Hunan Peoples R China Cent South Univ Xiangya Sch Med Dept Histol & Embryol Changsha Peoples R China

Triple negative breast cancer (TNBC) is a type of breast cancer with the worst clinical outcome. TNBC is not sensitive to typical endocrine therapy and targeted therapy. Thioredoxin interacting protein (txnip), known as a tumor suppressor, is related to oxidative stress and energy metabolism. However, the clinical significance of txnip in TNBC and mechanism in immunity have not been fully reported. In this study, we found that the expression of txnip was downregulated obviously in TNBC tissues and negatively correlated with tumor grade by comprehensive bioinformatics analysis and immunohistochemistry staining of 108 TNBC tissues. Through in vivo and in vitro experiments, we identified txnip as a tumor suppressor in TNBC. By bulk mRNA and scRNA analysis, we found that txnip could enhance immune response in TNBC and was a potential biomarker for cancer immunity and immunotherapy. We also performed the drug susceptibility analysis to reveal the thera-peutic value of txnip. In conclusion, our findings demonstrated that txnip was a tumor suppressor in TNBC and was involved in tumor malignancy progression. txnip was a potential biomarker for immunotherapy and promising molecular therapeutic target.

关键词： txnip Triple negative breast cancer Prognosis Tumor microenvironment Immunotherapy Therapeutic target

来源：评论

学校读者我要写书评

暂无评论

Diagnostic and predictive significance of the ferroptosis-related gene txnip in lung adenocarcinoma stem cells based on multi-omics

引用

TRANSLATIONAL ONCOLOGY 2024年 45卷 101926-101926页

作者： Zheng, Yuanyuan Yang, Wei Wu, Weixuan Jin, Feng Lu, Dehua Gao, Jing Wang, Shubin Peking Univ Shenzhen Hosp Shenzhen Peking Univ Hong Kong Univ Sci & Technol Canc InstDept OncolShenzhen Key Lab Gastrointes Shenzhen 518036 Peoples R China GeneMind Biosci Co Ltd Shenzhen 518000 Peoples R China Jinan Univ Shenzhen Peoples Hosp Clin Med Coll 2 Dept Gen Practice Shenzhen 518020 Peoples R China Peking Univ Shenzhen Hosp Shenzhen Peking Univ Hong Kong Univ Sci & Technol Canc InstDept Radiat OncolShenzhen Key Lab Gast Shenzhen 518036 Peoples R China

Background: Lung cancer stands as the foremost cause of cancer-related fatalities globally. The presence of cancer stem cells (CSCs) poses a challenge, rendering current targeted tumor therapies ineffective. This study endeavors to investigate a novel therapeutic approach focusing on ferroptosis and delves into the expression of ferroptosisrelated genes within lung CSCs. Methods: We systematically examined RNA-seq datasets derived from lung tumor cells (LTCs) and lung cancer stem cells (LSCs), as previously investigated in our research. Our focus was on analyzing differentially expressed genes (DEGs) related to ferroptosis. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), we conducted functional analysis of these ferroptosis-related DEGs. Additionally, we employed protein-protein interaction networks to identify hub genes. LC-MS/MS analysis of LTCs and LSCs was conducted to pinpoint the crucial ferroptosis-related gene-thioredoxin-interacting protein (txnip).Further, we delved into the immune cell infiltration landscape of LTCs and LSCs, examining the correlation between txnip and lung adenocarcinoma (LUAD) using data from The Cancer Genome Atlas (TCGA) database. To complement these findings, we measured the expression levels of txnip, glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4 (NCOA4) in LUAD tissues through immunohistochemistry (IHC) staining. Results: A total of 651 DEGs were identified, with 17 of them being ferroptosis-related DEGs. These seventeen genes were categorized into four groups: driver genes, suppressor genes, unclassified genes, and inducer genes. Enrichment analysis revealed significant associations with oxidative stress, cell differentiation, tissue development, and cell death processes. The RNA-seq analysis demonstrated consistent gene expression patterns with protein expression, as evidenced by mass spectrometry analysis. Among the identified genes, SFN and txnip were singled out as hub gene

关键词： Lung adenocarcinoma cancer Cancer stem cells Ferroptosis txnip Multi-omics analysis

来源：评论

学校读者我要写书评

暂无评论

Tanshinone IIA attenuates ox-LDL-induced endothelial cell injury by inhibiting NF-kapaB pathway via circ_0000231/miR-590-5p/txnip axis

引用

CHEMICAL BIOLOGY & DRUG DESIGN 2024年第1期103卷 e14394页

作者： Chen, Zhu Zhao, Jiaai Wang, Siwang Li, Qiang Jinzhou Med Univ Affiliated Hosp 1 Dept Neurol Jinzhou Peoples R China Jinzhou Med Univ Affiliated Hosp 1 Dept Cardiol Jinzhou Peoples R China Jinzhou Med Univ Affiliated Hosp 1 Dept Cardiol 2 Renmin Rd Jinzhou 121000 Peoples R China

Tanshinone IIA (TSIIA) exhibits inhibitory function in atherosclerosis (AS) progression, and circular RNAs (circRNAs) are pivotal regulators in AS. However, the relation between TSIIA and circ_0000231 in AS pathogenesis remains unknown. In this study, oxidized low-density lipoprotein (ox-LDL) was used to establish AS cell model. Treatment of ox-LDL inhibited cell growth but promoted apoptosis, inflammation, and oxidative stress. Then, TSIIA was shown to attenuate ox-LDL-induced endothelial injury. Furthermore, the protective effect of TSIIA against ox-LDL-induced endothelial cell injury was reversed by circ_0000231. Circ_0000231 was identified as a miR-590-5p sponge. Also, miR-590-5p downregulation restored the protection of TSIIA for endothelial cell function. Moreover, circ_0000231 was found to upregulate thioredoxin interacting protein (txnip) level via targeting miR-590-5p. txnip overexpression mitigated the regulatory function of circ_0000231 knockdown after co-treatment with ox-LDL and TSIIA. txnip upregulation recovered the inhibitory regulation of TSIIA in ox-LDL-induced cell damage. In addition, TSIIA inactivated NF-kapaB (NF-kappa B) signaling pathway via regulating miR-590-5p/txnip axis by downregulating circ_0000231. All these results suggested that TSIIA inhibited ox-LDL-induced AS progression in endothelial cells by affecting NF-kappa B pathway via circ_0000231/miR-590-5p/txnip.

关键词： atherosclerosis circ_0000231 miR-590-5p NF-kapaB pathway Tanshinone IIA txnip

来源：评论

学校读者我要写书评

暂无评论

REDD1 knockdown ameliorates endothelial cell senescence through repressing txnip-mediated oxidative stress

引用

MECHANISMS OF AGEING AND DEVELOPMENT 2024年 221卷 111962页

作者： Chen, Qingqiu Hu, Rong Qiu, Hongmei Li, Shan Xiang, Peng Lu, Yining Wang, Xianmin Wang, Tongchuan Zhou, Lan Zhang, Wanping Wen, E. Ma, Limei Yu, Chao Chongqing Med Univ Coll Pharm Chongqing Key Lab Pharmaceut Metab Res Chongqing 400010 Peoples R China Chongqing Med Univ Affiliated Hosp 2 Precis Med Ctr Chongqing Peoples R China

Endothelial cell senescence characterized by reactive oxygen species (ROS) accumulation and chronic inflammation is widely recognized as a key contributor to atherosclerosis (AS). Regulated in development and DNA damage response 1 (REDD1), a conserved stress-response protein that regulates ROS production, is involved in the pathogenesis of various age-related diseases. However, the role of REDD1 in endothelial cell senescence is still unclear. Here, we screened REDD1 as a differentially expressed senescence-related gene in the AS progression using bioinformatics methods, and validated the upregulation of REDD1 expression in AS plaques, senescent endothelial cells, and aging aorta by constructing AS mice, D-galactose (DG)-induced senescent endothelial cells and DG-induced accelerated aging mice, respectively. siRNA against REDD1 could improve DGinduced premature senescence of endothelial cells and inhibit ROS accumulation, similar to antioxidant NAcetylcysteine (NAC) treatment. Meanwhile, NAC reduced the upregulation of REDD1 induced by DG, supporting the positive feedback loop between REDD1 and ROS contributes to endothelial cell senescence. Mechanistically, the regulatory effect of REDD1 on ROS might be related to the txnip-REDD1 interaction in DGinduced endothelial cell senescence. Collectively, experiments above provide evidence that REDD1 participates in endothelial cell senescence through repressing txnip-mediated oxidative stress, which may be involved in the progression of atherosclerosis.

关键词： REDD1 txnip Endothelial cell senescence Oxidative stress Atherosclerosis

来源：评论

学校读者我要写书评

暂无评论

Cilostazol protects against degenerative cervical myelopathy injury and cell pyroptosis via txnip-NLRP3 pathway

引用

CELL DIVISION 2024年第1期19卷 2页

作者： Xu, Fei Tian, Zhuo Wang, Zhengguang Yantai Hosp Tradit Chinese Med Dept Neck Shoulder & Lumbocrural Pain 39 Xingfu Rd Yantai 264000 Shandong Peoples R China Yantai Hosp Tradit Chinese Med Dept Gen Surg Yantai Shandong Peoples R China

Degenerative cervical myelopathy (DCM) is one of the most common and serious neurological diseases. Cilostazol has protective effects of anterior horn motor neurons and prevented the cell apoptosis. However, there was no literatures of Cilostazol on DCM. In this study, we established the DCM rat model to detect the effects of Cilostazol. Meanwhile, the neurobehavioral assessments, histopathology changes, inflammatory cytokines, Thioredoxin-interacting protein (txnip), NOD-like receptor pyrin domain containing 3 (NLRP3) and pro-caspase-1 expressions were detected by Basso, Beattie, and Bresnahan score assessment, Hematoxylin and Eosin Staining, Enzyme-linked immunosorbent assay, immunofluorescence and Western blotting, respectively. After treated with Cilostazol, the Basso, Beattie, and Bresnahan (BBB) score, inclined plane test and forelimb grip strength in DCM rats were significantly increased meanwhile the histopathology injury and inflammatory cytokines were decreased. Additionally, txnip, NLRP3 and pro-caspase-1 expressions levels were decreased in Cilostazol treated DCM rats. Interestingly, the using of sitxnip significantly changed inflammatory cytokines, txnip, NLRP3 and pro-caspase-1 expressions, however there was no significance between sitxnip and Cilostazol + sitxnip group. These observations showed that Cilostazol rescues DCM injury and ameliorates neuronal destruction mediated by txnip/NLRP3/caspase-1 and pro-inflammatory cytokines. As a result of our study, these findings provide further evidence that Cilostazol may represent promising therapeutic candidates for DCM.

关键词： Degenerative cervical myelopathy Cilostazol Pyroptosis txnip NLRP3

来源：评论

学校读者我要写书评

暂无评论

Silibinin induces metabolic crisis in triple-negative breast cancer cells by modulating EGFR-MYC-txnip axis: potential therapeutic implications

引用

FEBS JOURNAL 2021年第2期288卷 471-485页

作者： Iqbal, Mohammad Askandar Chattopadhyay, Shilpi Siddiqui, Farid Ahmad Rehman, Asad Ur Siddiqui, Shumaila Prakasam, Gopinath Khan, Asifa Sultana, Sarwat Bamezai, Rameshwar N. K. Jamia Millia Islamia Fac Nat Sci Dept Biotechnol New Delhi 110025 India Jamia Hamdard Deemed Univ Sch Chem & Life Sci Dept Toxicol New Delhi India Univ Turku Turku Ctr Biotechnol Biocity Finland Abo Akad Univ Biocity Finland Univ Delhi Dr BR Ambedkar Ctr Biomed Res Delhi India Jawaharlal Nehru Univ Sch Life Sci New Delhi India Univ Texas Southwestern Med Ctr Dallas Dept Internal Med Dallas TX 75390 USA Jamia Millia Islamia Fac Nat Sci Dept Biosci New Delhi India

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment modalities and poor prognosis. Metabolic reprogramming in cancer is considered a hallmark of therapeutic relevance. Here, we report disruption of metabolic reprogramming in TNBC cells by silibinin via modulation of EGFR-MYC-txnip signaling. Metabolic assays combined with LC-MS-based metabolomics revealed inhibition of glycolysis and other key biosynthetic pathways by silibinin, to induce metabolic catastrophe in TNBC cells. Silibinin-induced metabolic suppression resulted in decreased cell biomass, proliferation, and stem cell properties. Mechanistically, we identify EGFR-MYC-txnip as an important regulator of TNBC metabolism and mediator of inhibitory effects of silibinin. Highlighting the clinical relevance of our observations, the analysis of METABRIC dataset revealed deregulation of EGFR-MYC-txnip axis in TNBC and association of EGFR(high)-MYChigh-txnip(low)signature with aggressive glycolytic metabolism and poor disease-specific and metastasis-free survival. Importantly, combination treatment of silibinin or 2-deoxyglucose (glycolysis inhibitor) with paclitaxel synergistically inhibited proliferation of TNBC cells. Together, our results highlight the importance of EGFR-MYC-txnip axis in regulating TNBC metabolism, demonstrate the anti-TNBC activity of silibinin, and argue in favor of targeting metabolic vulnerabilities of TNBC, at least in combination with mainstay chemotherapeutic drugs, to effectively treat TNBC patients.

关键词： cancer metabolism EGFR MYC silibinin triple-negative breast cancer txnip

来源：评论

学校读者我要写书评

暂无评论

Histone deacetylase 10 exerts antitumor effects on cervical cancer via a novel microRNA-223/txnip/Wnt/β-catenin pathway

引用

IUBMB LIFE 2021年第4期73卷 690-704页

作者： Zhu, Jinming Han, Shichao Dalian Univ Affiliated Zhongshan Hosp Dept Oncol Dalian Peoples R China Dalian Med Univ Affiliated Hosp 2 Dept Gynecol 467 Zhong Shan Rd Dalian 116021 Liaoning Peoples R China

Dysfunction of histone deacetylase 10 (HDAC10) has been suggested in the carcinogenesis of cervical cancer (CC). However, its association with microRNAs (miRNAs) in CC remains exclusive. Hence, this study aims to probe the role of HDAC10 in regulating CC cell proliferation, migration, and invasion and its correlation with the screened-out miRNA target. Microarray analysis and RT-qPCR revealed that HDAC10 expressed poorly in CC cells relative to human immortalized endocervical cells (End1/E6E7). Moreover, HDAC10 downregulation predicted poor survival for patients with CC. Overexpression of HDAC10 reduced CC cell biological activities in vitro and tumor growth and lung metastases in vivo. miR-223, upregulated in CC, was regulated by HDAC10 through histone acetylation, while miR-223 inhibited the effects of HDAC10 overexpression in CC. miR-223 targeted the 3 '-UTR of thioredoxin interacting protein (txnip) and suppressed its expression, leading to increased CC development in vitro and in vivo. txnip overexpression impaired Wnt/beta-catenin pathway activity in CC cells.

关键词： cervical cancer HDAC10 microRNA-223 txnip Wnt/beta-catenin pathway

来源：评论

学校读者我要写书评

暂无评论

Tumor cells derived-extracellular vesicles transfer miR-3129 to promote hepatocellular carcinoma metastasis by targeting txnip

引用

DIGESTIVE AND LIVER DISEASE 2021年第4期53卷 474-485页

作者： Yang, Yang Mao, Feifei Guo, Lei Shi, Jie Wu, Mengchao Cheng, Shuqun Guo, Weixing Second Mil Med Univ Affiliated Hosp 3 Dept Hepat Surg 6 Shanghai 200438 Peoples R China Tongji Univ Sch Med Shanghai Peoples Hosp 10 Ctr Canc Shanghai 200072 Peoples R China

Background: Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer. Extracellular vesicles (EV)-mediated microRNA (miRNA) delivery is critical in cancer metastasis. We aimed to identify the mechanism of HCC cell-derived EVs-mediated miR-3129 in HCC. Methods: After EVs isolation and identification, miR-3129 expression in plasma EVs was evaluated and its diagnostic efficiency was analyzed. miR-3129 inhibitor was transfected into HepG2 and SMMC7721 cells, and cell malignant episodes were assessed. HCC cells were incubated with EVs from MHCC-97H cells and transfected with miR-3129 inhibitor and/or txnip. The nude mice were injected with MHCC-97H cells-EV or MHCC-97H cells-EV/miR-3129 inhibitor, and HCC growth and metastasis were assessed. Results: miR-3129 was highly expressed in plasma EVs from HCC patients, which was the essential diagnostic biomarker for HCC. miR-3129 downregulation inhibited the malignant episodes of HCC cells. MHCC-97H cell-EVs were absorbed by HCC cells and transferred miR-3129 to HCC cells. EVs-carried miR3129 promoted malignant episodes of HCC cells, which were weakened by miR-3129 inhibition in EVs. miR-3129 targeted txnip. txnip overexpression averted the effect of EVs-carried miR-3129 in HCC. In vivo, MHCC-97H cell-EVs transferred miR-3129 to facilitate HCC growth and metastasis. Conclusion: MHCC-97H cell-EVs transferred miR-3129 to promote HCC metastasis by targeting txnip. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： Hepatocellular carcinoma Extracellular vesicles Metastasis microRNA-3129 txnip Epithelial-mesenchymal-transition

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：