检索结果-内蒙古大学图书馆

PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through txnip-mediated oxidative stress

引用

CELLULAR & MOLECULAR BIOLOGY LETTERS 2024年第1期29卷 110页

作者： Wang, Shimin Wang, Xiaolin Qin, Changhong Liang, Ce Li, Wei Ran, Ai Ma, Qiang Pan, Xiaojuan Yang, Feifei Ren, Junwu Huang, Bo Liu, Yuying Zhang, Yuying Li, Haiping Ning, Hao Jiang, Yan Xiao, Bin Chongqing Med Univ Coll Pharm Chongqing 400016 Peoples R China Chongqing Univ Canc Hosp Dept Pharm Chongqing 400030 Peoples R China Zunyi Med Univ Key Lab Basic Pharmacol Minist Educ Zunyi 563006 Guizhou Peoples R China Zunyi Med Univ Joint Int Res Lab Ethnomed Minist Educ Zunyi 563006 Guizhou Peoples R China

BackgroundGastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly *** assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT-qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1's regulation of autophagy in *** findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (txnip) mRNA, leading to increased txnip-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in ***1 knockdown impairs GC progression by directly binding to txnip mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promisi

关键词： GC Autophagy PTBP1 txnip Chloroquine

来源：评论

学校读者我要写书评

暂无评论

Chronic intermittent hypoxia-induced mitochondrial dysfunction mediates endothelial injury via the txnip/NLRP3/IL-1? signaling pathway

引用

FREE RADICAL BIOLOGY AND MEDICINE 2021年 165卷 401-410页

作者： Yan, Ya Ru Zhang, Liu Lin, Ying Ni Sun, Xian Wen Ding, Yong Jie Li, Ning Li, Hong Peng Li, Shi Qi Zhou, Jian Ping Li, Qing Yun Shanghai Jiao Tong Univ Ruijin Hosp Dept Resp & Crit Care Med Sch Med Shanghai 200025 Peoples R China Shanghai Jiao Tong Univ Inst Resp Dis Sch Med Shanghai 200025 Peoples R China

Oxidative stress and inflammation induced by chronic intermittent hypoxia (CIH) are trigger factors of cardiovascular diseases in patients with obstructive sleep apnea (OSA). This study aimed to investigate the role of CIHinduced mitochondrial dysfunction in vascular endothelial injury both in vivo and in vitro. Human umbilical vein endothelial cells and Sprague Dawley rats were exposed to CIH. CIH promoted the production of intracellular reactive oxygen species, caused mitochondrial dysfunction, and induced cell apoptosis in human umbilical vein endothelial cells. RNA-Seq analysis revealed that the NOD-like receptor signaling pathway was involved in endothelial injury induced by CIH. txnip/NLRP3/IL-1? pathway was found to be upregulated by CIH. Knockdown of TNXIP rescued the endothelial cells from CIH-induced apoptosis, indicating that activation of the txnip/NLRP3/IL-1? pathway mediated the CIH-induced endothelial apoptosis. Administration of the mitochondria-targeted antioxidant mito-TEMPO improved mitochondrial function and suppressed upregulation of the txnip/NLRP3/IL-1? pathway, thereby alleviating CIH-induced endothelial apoptosis. In vivo experiments confirmed the results, where mito-TEMPO was found to ameliorate endothelial injury in rat aortas exposed to CIH. The results imply that CIH-induced mitochondrial dysfunction mediates endothelial injury implication of txnip/NLRP3/IL-1? signaling pathway.

关键词： Obstructive sleep apnea Chronic intermittent hypoxia Mitochondrial dysfunction txnip NLRP3 inflammasome Endothelial injury

来源：评论

学校读者我要写书评

暂无评论

Effect of Sleeve Gastrectomy on Plasma Thioredoxin-Interacting Protein (txnip)

引用

OBESITY SURGERY 2021年第11期31卷 4829-4835页

作者： Chu, Yuxiao Widjaja, Jason Hong, Jian Dolo, Ponnie Robertlee Zhu, Xiaocheng Yao, Libin Xuzhou Med Univ Affiliated Hosp Dept Gastrointestinal Surg Xuzhou 221002 Jiangsu Peoples R China

Purpose The mechanism in which bariatric surgery induces diabetes remission is still poorly understood. This study proposes Thioredoxin-interacting protein (txnip) as a possible factor for the anti-diabetic mechanism after sleeve gastrectomy (SG). Materials and Methods Plasma txnip level in obesity patients with diabetes (T2D, N = 20), obesity patients without diabetes (NDO, N = 20), and patients without obesity and diabetes (lean, N = 10) were assessed before surgery and at 1 and 12 months after SG. Results Preoperative txnip level was significantly higher in T2D (196.4 +/- 76.0 pg/ml) and NDO (149.7 +/- 94.1 pg/ml) patients when compared with lean patients (98.7 +/- 22.7 pg/ml) (p-value < 0.05). At 1 month and 12 months postoperatively, the txnip levels were reduced significantly from the preoperative levels in the T2D and NDO patients (p-value < 0.05). Before surgery, a correlation between txnip and fasting blood glucose (FBG) (r(2) = 0.1585, p-value = 0.0109), HbA1C (r(2) = 0.2120, p-value = 0.0028), and insulin (r(2) = 0.1217, p-value = 0.0274) was observed. At 12 months after surgery, the reduction of txnip was also correlated with the degree of FBG (r(2) = 0.1038, p-value = 0.0426), HbA1C (r(2) = 0.2459, p-value = 0.0011), and insulin (r(2) = 0.1365, p-value = 0.0190) reduction. Conclusion Plasma txnip level is elevated in obesity patients with/without diabetes. SG resulted in a significant reduction of plasma txnip level which is correlated with the degree of FBG, HbA1C, and insulin reduction. Regulation of txnip could be part of the mechanism of diabetes remission after bariatric surgery.

关键词： Sleeve gastrectomy txnip Type 2 diabetes Obesity Diabetes remission

来源：评论

学校读者我要写书评

暂无评论

CircRNA cRAPGEF5 inhibits the growth and metastasis of renal cell carcinoma via the miR-27a-3p/txnip pathway

引用

CANCER LETTERS 2020年 469卷 68-77页

作者： Chen, Qiong Liu, Tao Bao, Yi Zhao, Tangliang Wang, Jie Wang, Hui Wang, Anbang Gan, Xinxin Wu, Zhenjie Wang, Linhui Second Mil Med Univ Changzheng Hosp Dept Urol 415 Fengyang Rd Shanghai 200003 Peoples R China

Circular RNAs (circRNAs) are reported to act as important regulators in cancers. CircRNA RAPGEF5 (cRAPGEF5) is derived from exons 2-6 of the RAPGEF5 gene and may promote papillary thyroid cancer progression. However, the role of cRAPGEF5 in renal cell carcinoma (RCC) remains unclear. In this study, we found cRAPGEF5 to be significantly downregulated in RCC tissues. Among 245 RCC cases, cRAPGEF5 downregulation correlated positively with aggressive clinical characteristics and independently predicted poor overall survival and recurrence-free survival. Functional assays demonstrated that cRAPGEF5 suppresses RCC proliferation and migration in vitro and in vivo. Mechanistically, RNA Immunoprecipitation and circRNA in vivo precipitation assays showed that cRAPGEF5 functions as a sponge of oncogenic miR-27a-3p, which targets the suppressor gene txnip. Interactions between miR-27a-3p and cRAPGEF5 or txnip were confirmed by dual-luciferase reporter assays. In conclusion, cRAPGEF5 plays a role in suppressing RCC via the miR-27a-3p/txnip pathway and may serve as a promising prognostic biomarker and novel therapeutic target for RCC patients.

关键词： Circular RNA RAPGEFS miRNA sponge miR-27a-3p txnip

来源：评论

学校读者我要写书评

暂无评论

A novel txnip-based mechanism for Cx43-mediated regulation of oxidative drug injury

引用

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 2015年第10期19卷 2469-2480页

作者： Gao, Kun Chi, Yuan Zhang, Xiling Zhang, Hui Li, Gang Sun, Wei Takeda, Masayuki Yao, Jian Univ Yamanashi Interdisciplinary Grad Sch Med & Engn Dept Mol Signaling Chuo Ku Yamanashi Japan Nanjing Univ Chinese Med Affiliated Hosp Dept Nephrol Nanjing Jiangsu Peoples R China Univ Yamanashi Interdisciplinary Grad Sch Med & Engn Dept Urol Chuo Ku Yamanashi Japan Liaoning Canc Hosp & Inst Dept Urol Shenyang Liaoning Peoples R China

Gap junctions (GJs) play an important role in the regulation of cell response to many drugs. However, little is known about their mechanisms. Using an invitro model of cytotoxicity induced by geneticin (G418), we explored the potential signalling mechanisms involved. Incubation of cells with G418 resulted in cell death, as indicated by the change in cell morphology, loss of cell viability and activation of caspase-3. Before the onset of cell injury, G418 induced reactive oxygen species (ROS) generation, activated oxidative sensitive kinase P38 and caused a shift of connexin 43 (Cx43) from non-phosphorylated form to hyperphosphorylated form. These changes were largely prevented by antioxidants, suggesting an implication of oxidative stress. Downregulation of Cx43 with inhibitors or siRNA suppressed the expression of thioredoxin-interacting protein (txnip), activated Akt and protected cells against the toxicity of G418. Further analysis revealed that inhibition of txnip with siRNA activated Akt and reproduced the protective effect of Cx43-inhibiting agents, whereas suppression of Akt sensitized cells to the toxicity of G418. Furthermore, interference of txnip/Akt also affected puromycin- and adriamycin-induced cell injury. Our study thus characterized txnip as a presently unrecognized molecule implicated in the regulatory actions of Cx43 on oxidative drug injury. Targeting Cx43/txnip/Akt signalling cascade might be a promising approach to modulate cell response to drugs.

关键词： connexin 43 gap junction oxidative stress cytotoxicity txnip Akt

来源：评论

学校读者我要写书评

暂无评论

W2476 represses txnip transcription via dephosphorylation of FOXO1 at Ser319

引用

CHEMICAL BIOLOGY & DRUG DESIGN 2021年第5期97卷 1089-1099页

作者： Zhong, Li Liu, Qing Liu, Qiaofeng Zhang, Shikai Cao, Yongbing Yang, Dehua Wang, Ming-Wei Chinese Acad Sci Natl Ctr Drug Screening CAS Key Lab Receptor Res Shanghai Inst Mat Med Shanghai 201203 Peoples R China Univ Chinese Acad Sci Beijing Peoples R China Fudan Univ Sch Pharm Shanghai Peoples R China Shanghai Univ Tradit Chinese Med Shanghai TCM Integrated Hosp Shanghai Peoples R China

Thioredoxin-interacting protein (txnip) overexpression is implicated in the pathogenesis of type 2 diabetes. Previous studies have shown that a small molecule compound (W2476) was able to improve beta-cell dysfunction and exert therapeutic effects in diabetic mice via repression of txnip signaling pathway. The impact of W2476 on txnip transcription was thus investigated using the chromatin immunoprecipitation method. It was found that W2476 promotes competitive binding of forkhead box O1 transcription factor (FOXO1) to the carbohydrate response element (ChoRE) sequence associated with ChoRE-binding protein (ChREBP)/Mlx interacting protein-like(Mlx) complexes. This interaction hinders the attachment of histone acetyltransferase p300 and reduces histone H4 acetylation on the txnip promoter, leading to decreasing txnip transcription.

关键词： chromatin immunoprecipitation diabetes transcription txnip W2476

来源：评论

学校读者我要写书评

暂无评论

miR-125b enhances metastasis and progression of cancer via the txnip and HIF1α pathway in pancreatic cancer

引用

CANCER BIOMARKERS 2021年第1期31卷 27-38页

作者： Wang, Pengli Zheng, Dan Qi, Hongyang Gao, Qi Xinxiang Cent Hosp Dept Gastroenterol 56 Jinsui Ave Xinxiang 453000 Henan Peoples R China Xinxiang Cent Hosp Dept Endocrinol Xinxiang Henan Peoples R China

BACKGROUND: MicroRNAs (miRNAs) play potential role in the development of various types of cancer conditions including pancreatic cancer (PC) targeting several cellular processes. Present study was aimed to evaluate function of miR-125b and the mechanism involved in PC. METHODS: Cell migration, MTT and BrdU study was done to establish the migration capability, cell viability and cell proliferation respectively. Binding sites for miR-125b were recognized by luciferase assay, expression of protein by western blot and immunofluorescence assay. In vivo study was done by BALB/c nude xenograft mice for evaluating the function of miR-125b. RESULTS: The study showed that expression of miR-125b was elevated in PC cells and tissues, and was correlated to proliferation and migration of cells. Also, over-expression of miR-125b encouraged migration, metastasis and proliferation of BxPC-3 cells, the suppression reversed it. We also noticed that thioredoxin-interacting protein (txnip) was the potential target of miR-125b. The outcomes also suggested that miR-125b governed the expression of txnip inversely via directly attaching to the 3'-UTR activating hypoxia-inducible factor 1 alpha (HIF1 alpha). Looking into the relation between HIFI cx and txnip, we discovered that txnip caused the degradation and export of HIF1 alpha by making a complex with it. CONCLUSION: The miR-125b-txnip-HIF1 alpha pathway may serve useful strategy for diagnosing and treating PC.

关键词： Pancreatic cancer miR-125b HIF1 alpha txnip

来源：评论

学校读者我要写书评

暂无评论

Resveratrol improves diabetes-induced cognitive dysfunction in part through the miR-146a-5p/txnip axis

引用

KAOHSIUNG JOURNAL OF MEDICAL SCIENCES 2023年第4期39卷 404-415页

作者： Hu, Ying Zhang, Qin Wang, Jian-Cheng Wang, Jiao Liu, Ying Zhu, Ling-Yan Xu, Ji-Xiong Nanchang Univ Affiliated Hosp 1 Dept Endocrinol & Metab 17 Yongwaizheng St Nanchang 330006 Jiangxi Peoples R China Jiangxi Clin Res Ctr Endocrine & Metab Dis 17 Yongwaizheng St Nanchang 330006 Jiangxi Peoples R China Natl Clin Res Ctr Metab Dis Jiangxi Branch 17 Yongwaizheng St Nanchang 330006 Jiangxi Peoples R China Med Ctr Anesthesiol & Pain Dept Anesthesiol & Operat Med Nanchang Peoples R China

Resveratrol (RSV) has been shown to have a neuroprotective effect in various central nervous system disorders, although the role of RSV in diabetes-induced cognitive dysfunction is still not fully elucidated. Here, we investigated whether RSV improved diabetes-related cognitive dysfunction in vivo and in vitro. We induced a rat diabetic model with a high-fat and high-sucrose diet followed by intraperitoneal injection of streptozotocin and a diabetic neuron cell model by stimulation with high levels of glucose. We observed that RSV improved impairment in spatial learning and memory in the Morris water maze test (MWM) and novel object recognition test (ORT) in diabetic rats. RSV reversed the reduced miR-146a-5p and upregulated thioredoxin-interacting protein (txnip) and inhibited the diabetes-induced increase in interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha levels in vivo and in vitro. RSV also inhibited diabetes-induced endoplasmic reticulum stress (ESR) by reducing ESR-related protein expression in vivo and in vitro. Moreover, inhibition of miR-146a-5p partially abolished the protective effects of RSV in HG-treated primary neurons. Additionally, we used starBase to predict that miR-146a-5p interacts with txnip, which we then verified using a luciferase reporter gene assay. We further observed that miR-146a-5p regulates the mRNA and protein expression of txnip in vitro, indicating that the miR-146a-5p/txnip axis is involved in the regulation of cognitive dysfunction in a rat diabetic model. Collectively, these results demonstrate that RSV plays a neuroprotective role in diabetes-associated cognitive dysfunction at least in part through regulation of the miR-146a-5p/txnip axis.

关键词： diabetes-induced cognitive dysfunction miR-146a-5p resveratrol txnip

来源：评论

学校读者我要写书评

暂无评论

RNase MCPIP1 regulates hepatic peroxisome proliferator-activated receptor gamma via txnip/PGC-1 alpha pathway

引用

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS 2019年第10期000卷 1458-1471页

作者： Pydyn, Natalia Kadluczka, Justyna Kus, Edyta Pospiech, Ewelina Losko, Magdalena Fu, Mingui Jura, Jolanta Kotlinowski, Jerzy Jagiellonian Univ Fac Biochem Biophys & Biotechnol Dept Gen Biochem Gronostajowa 7 PL-30387 Krakow Poland Jagiellonian Univ Jagiellonian Ctr Expt Therapeut Bobrzynskiego 14 PL-30348 Krakow Poland Jagiellonian Univ Malopolska Ctr Biotechnol Krakow Poland Univ Missouri Sch Med Trauma Res Ctr Dept Biomed Sci & Shock Kansas City MO 64108 USA

Monocyte chemoattractant protein-l-induced protein-1 (MCPIP1) acts as an endonuclease that degrades selected mRNAs, viral RNAs and pre-miRNAs. MCPIP1 inhibits adipogenesis by degradation of C/EBP beta mRNA and adipogenesis-related miRNA, however its role in the regulation of hepatic lipid homeostasis is unknown. In this study, we investigated the role of MCPIP1 in the regulation of lipid metabolism in hepatocytes. C57BL/6 mice were fed a high-fat diet (HFD) for 2-20 weeks and next primary hepatocytes and adipose tissue were isolated. For in vitro experiments we used murine primary hepatocytes, control HepG2 cells and HepG2 with over-expressed or silenced MCPIP1. We found that Mcpip1 levels were lower in primary hepatocytes isolated from HFD-fed mice than in control cells starting at 4 weeks of a HFD. Level of Mcpip1 was also depleted in visceral fat isolated from obese and glucose-intolerant mice characterized by fatty liver disease. We showed that MCPIP1 overexpression in HepG2 cells treated with oleate induces the level and activity of peroxisome proliferator-activated receptor gamma (PPAR gamma). This phenotype was reverted upon silencing of MCPIP1 in HepG2 cells and in primary hepatocytes lacking MCPIP1 protein. MCPIP1 activated the PPAR gamma transcription factor via the thioredoxin-interacting protein (txnip)/peroxisome proliferator-activated receptor gamma coactivator 1- alpha (PGC-1 alpha) pathway. MCPIP1 contributes to lipid metabolism in hepatocytes by regulating the txnip/PGC-1 alpha/PPAR gamma pathway.

关键词： MCPIP1 Peroxisome proliferator-activated receptor gamma txnip Obesity Fatty liver

来源：评论

学校读者我要写书评

暂无评论

txnip induces growth arrest and enhances ABT263-induced apoptosis in mixed-lineage leukemia-rearranged acute myeloid leukemia cells

引用

FEBS OPEN BIO 2020年第8期10卷 1532-1541页

作者： Noura, Mina Matsuo, Hidemasa Koyama, Asami Adachi, Souichi Masutani, Hiroshi Kyoto Univ Grad Sch Med Dept Human Hlth Sci Kyoto Japan Tenri Hlth Care Univ Dept Clin Lab Sci 80-1 Bessho Cho Tenri Nara 6320018 Japan Kyoto Univ Grad Sch Med Dept Pediat Kyoto Japan

Thioredoxin-interacting protein (txnip) has been widely recognized as a tumor suppressor in various cancers, including liver, breast, and thyroid cancers. Although txnip is epigenetically silenced in acute myeloid leukemia (AML) cells, as in many cancer cells, its role in leukemogenesis remains elusive. Mixed-lineage leukemia (MLL) gene rearrangements in AML are associated with poor prognosis, and the development of a new treatment method is eagerly anticipated. In this study, we first reveal that lower expression of txnip is correlated with shortened overall survival periods in AML patients. Moreover, we demonstrated that txnip overexpression significantly suppresses proliferation in AML cells harboring MLL fusion genes. txnip promotes autophagy by increasing expression of the autophagy protein, Beclin 1, and lipidation of LC3B. We also show that txnip overexpression combined with ABT263, a potent inhibitor of Bcl-2 and Bcl-xL, is highly effective at inducing cell death in MLL-rearranged (MLL-r) AML cells. In summary, this study provides insights into the molecular mechanism of txnip-mediated tumor suppression and furthermore underscores the potential of txnip as a promising therapeutic target for MLL-r AML.

关键词： AML autophagy MLL txnip

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：