18 results on '"Gongfa Wu"'
Search Results
2. Assessment of sepsis-associated encephalopathy by quantitative magnetic resonance spectroscopy in a rat model of cecal ligation and puncture
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Siqi Liu, Zhifeng Liu, Gongfa Wu, Haoyi Ye, Zhihua Wu, Zhengfei Yang, and Shanping Jiang
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Sepsis ,Cecal ligation and puncture ,Brain injury ,1H-MRS ,Neurological deficit ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive technique to quantify neurometabolic compounds in the living brain. We used 1H-MRS to evaluate the brain metabolites in a rat model of Sepsis-associated encephalopathy (SAE) established by cecal ligation and puncture (CLP). 36 male Sprague-Dawley rats were randomly divided into sham and CLP groups. Each group was further divided into three subgroups: subgroup O, subgroup M, and subgroup N. Neurological function assessments were performed on the animals in the subgroup O and subgroup N at 24 h, 48 h, and 72 h. The animals in the subgroup M were examined by magnetic resonance imaging (MRI) at 12 h after CLP. Compared with the sham group, the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the hippocampus was significantly lower in the CLP group. The respective ratios of lactate (Lac), myo-inositol (mIns), glutamate and glutamine (Glx), lipid (Lip), and choline (Cho) to Cr in the CLP group were clearly higher than those in the sham group. Cytochrome c, intimately related to oxidative stress, was elevated in the CLP group. Neurofilament light (NfL) chain and glial fibrillary acidic protein (GFAP) scores in the CLP group were significantly higher than those in the sham group, while zonula occludens-1 (ZO-1) was downregulated. Compared with the sham group, the CLP group displayed higher values of oxygen extraction fraction (OEF), central venous–arterial partial pressure of carbon dioxide (P (cv-a) CO2), and central venous lactate (VLac). In contrast, jugular venous oxygen saturation (SjvO2) declined. In the present study, 1H-MRS could be used to quantitatively assess brain injury in terms of microcirculation disorder, oxidative stress, blood–brain barrier disruption, and glial cell activation through changes in metabolites within brain tissue.
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- 2024
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3. Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis
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Jianguo Wang, Qiang Jiang, Oluwasijibomi Damola Faleti, Chi-Man Tsang, Min Zhao, Gongfa Wu, Sai-Wah Tsao, Minyi Fu, Yuxiang Chen, Tengteng Ding, Tuotuo Chong, Yufei Long, Xu Yang, Yuanbin Zhang, Yunxi Cai, Hanzhao Li, Manli Peng, Xiaoming Lyu, and Xin Li
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antiangiogenesis ,exosome ,nasopharyngeal carcinoma ,miRNA ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors.
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- 2020
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4. N-acetylcysteine alleviates post-resuscitation myocardial dysfunction and improves survival outcomes via partly inhibiting NLRP3 inflammasome induced-pyroptosis
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Fenglian He, Guanghui Zheng, Jingying Hou, Qiaohua Hu, Qin Ling, Gongfa Wu, Hui Zhao, Jin Yang, Yue Wang, Longyuan Jiang, Wanchun Tang, and Zhengfei Yang
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N-acetylcysteine ,Cardiopulmonary resuscitation ,Myocardial function ,Pyroptosis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background NOD-like receptor 3 (NLRP3) inflammasome is necessary to initiate acute sterile inflammation. Increasing evidence indicates the activation of NLRP3 inflammasome induced pyroptosis is closely related to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. N-acetylcysteine (NAC) is an antioxidant and plays a protective role in local myocardial I/R injury, while its effect on post-resuscitation myocardial dysfunction, as well as its mechanisms, remain elusive. In this study, we aimed to investigate the effect of NAC on post-resuscitation myocardial dysfunction in a cardiac arrest rat model, and whether its underlying mechanism may be linked to ROS and NLRP3 inflammasome-induced pyroptosis. Methods The rats were randomized into three groups: (1) sham group, (2) cardiopulmonary resuscitation (CPR) group, and (3) CPR + NAC group. CPR group and CPR + NAC group went through the induction of ventricular fibrillation (VF) and resuscitation. After return of spontaneous circulation (ROSC), rats in the CPR and CPR + NAC groups were again randomly divided into two subgroups, ROSC 6 h and ROSC 72 h, for further analysis. Hemodynamic measurements and myocardial function were measured by echocardiography, and western blot was used to detect the expression of proteins. Results Results showed that after treatment with NAC, there was significantly better myocardial function and survival duration; protein expression levels of NLRP3, adaptor apoptosis-associated speck-like protein (ASC), Cleaved-Caspase-1 and gasdermin D (GSDMD) in myocardial tissues were significantly decreased; and inflammatory cytokines levels were reduced. The marker of oxidative stress malondialdehyde (MDA) decreased and superoxide dismutase (SOD) increased with NAC treatment. Conclusions NAC improved myocardial dysfunction and prolonged animal survival duration in a rat model of cardiac arrest. Moreover, possibly by partly inhibiting ROS-mediated NLRP3 inflammasome-induced pryoptosis.
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- 2020
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5. Correction: EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.
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Xiaoming Lyu, Jianguo Wang, Xia Guo, Gongfa Wu, Yang Jiao, Oluwasijibomi Damola Faleti, Pengfei Liu, Tielian Liu, Yufei Long, Tuotuo Chong, Xu Yang, Jing Huang, Mingliang He, Chi Man Tsang, Sai Wah Tsao, Qian Wang, Qiang Jiang, and Xin Li
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
[This corrects the article DOI: 10.1371/journal.ppat.1007484.].
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- 2020
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6. EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.
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Xiaoming Lyu, Jianguo Wang, Xia Guo, Gongfa Wu, Yang Jiao, Oluwasijibomi Damola Faleti, Pengfei Liu, Tielian Liu, Yufei Long, Tuotuo Chong, Xu Yang, Jing Huang, Mingliang He, Chi Man Tsang, Sai Wah Tsao, Qian Wang, Qiang Jiang, and Xin Li
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. The occurrence of both events involves many key molecular changes including miRNA. However, EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis. Here, we reported that one of the key miRNAs encoded by EBV, EBV-miR-Bart1-5P, can significantly promote nasopharyngeal carcinoma (NPC) cell glycolysis and induces angiogenesis in vitro and in vivo. Mechanistically, EBV-miR-Bart1-5P directly targets the α1 catalytic subunit of AMP-activated protein kinase (AMPKα1) and consequently regulates the AMPK/mTOR/HIF1 pathway which impelled NPC cell anomalous aerobic glycolysis and angiogenesis, ultimately leads to uncontrolled growth of NPC. Our findings provide new insights into metabolism and angiogenesis of NPC and new opportunities for the development of targeted NPC therapy in the future.
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- 2018
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7. TRIM72 inhibits cell migration and epithelial-mesenchymal transition by attenuating FAK/Akt signalling in colorectal cancer
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Oluwasijibomi Damola Faleti, Haiqi Tan, Yibing Gong, Jing Huang, Simin Deng, Lizhen Qiu, Jinke Yao, Gongfa Wu, and Xiaoming Lyu
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TRIM72 (MG53) is a membrane repair protein with E3-ligase activity. In this study, we investigated its clinical significance and biological function in colorectal cancer (CRC). Reverse transcription-PCR was used to identify TRIM72 expression in primary CRC tumour tissue and the paired liver metastasis tumor samples. Results indicated that TRIM72 expression in paired liver metastases tissue was lower compared to the primary colon cancer tumour (p
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- 2023
8. Quantitative magnetic resonance imaging assessment of brain injury after successful cardiopulmonary resuscitation in a rat model of asphyxia cardiac arrest
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Gongfa Wu, Tangchun Liu, Jinhui Cai, Zhengfei Yang, Wanchun Tang, Zhifeng Liu, Guangyi Wang, Qingyu Liu, and Yue Wang
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Asphyxia ,medicine.medical_specialty ,Resuscitation ,medicine.diagnostic_test ,business.industry ,Cognitive Neuroscience ,medicine.medical_treatment ,Magnetic resonance imaging ,Return of spontaneous circulation ,medicine.disease ,Cerebral edema ,Behavioral Neuroscience ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Neurology ,Internal medicine ,Cardiology ,Medicine ,Effective diffusion coefficient ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Cardiopulmonary resuscitation ,medicine.symptom ,business ,Neuroradiology - Abstract
The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted magnetic resonance imaging (DWI) to measure changes in blood–brain barrier (BBB) permeability and cerebral edema over time in a rat model of asphyxial cardiac arrest (ACA). ACA was established by endotracheal tube clamping. Male rats were randomized into a sham group (n = 5) and three ACA groups (n = 18). After return of spontaneous circulation (ROSC), the rats were randomized to perform DWI and DCE-MRI exam in the 6 h, 24 h and 72 h timepoint (ROSC + 6 h, ROSC + 24 h, and ROSC + 72 h). Results shows that fifteen of 18 animals achieved successful resuscitation in the ACA groups. The average apparent diffusion coefficient(ADC) value of the whole brain in ROSC + 6 h was markedly lower than those of the sham, ROSC + 24 h, and ROSC + 72 h. The aquaporin-4(AQP4) score in ROSC + 6 h was significantly higher than those in the other groups, which were negatively correlated with the ADC values. The ratio of whole brain to masseter muscle of volume transfer constant (rKtrans), tissue interstitium-to-plasma rate constant(rKep), and fractional extra-cellular space volume(rVe) in ROSC + 6 h were all significantly higher than those in the sham, ROSC + 24 h, and ROSC + 72 h. The transforming growth factor β1(TGF-β1) and vascular endothelial growth factor A(VEGF-a) scores in ROSC + 6 h were significantly higher than those in the other groups, which were all positively correlated with rKtrans and rKep. In conclusions, brain injury is a frequent complication after CA and resuscitation. DWI and DCE-MRI can quantitatively evaluate brain injury in term of cerebral edema and BBB permeability after successful CPR.
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- 2021
9. Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis
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Sai Wah Tsao, Hanzhao Li, Tuotuo Chong, Oluwasijibomi Damola Faleti, Min Zhao, Qiang Jiang, Xin Li, Yufei Long, Yuxiang Chen, Jianguo Wang, Tengteng Ding, Manli Peng, Yun-xi Cai, Yuanbin Zhang, Minyi Fu, Gongfa Wu, Chi Man Tsang, Xiaoming Lyu, and Xu Yang
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0301 basic medicine ,Angiogenesis ,Biology ,Exosome ,law.invention ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,law ,Drug Discovery ,microRNA ,medicine ,exosome ,miRNA ,nasopharyngeal carcinoma ,lcsh:RM1-950 ,Cancer ,medicine.disease ,Microvesicles ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Suppressor ,Original Article ,antiangiogenesis - Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors., Graphical Abstract, Wang et al. generated a novel oncogenic pathway underlying angiogenesis regulation that involves EBV-miR-BART10-5p and hsa-miR-18a inhibiting tumor suppressor Spry3 and its downstream targets. They established a synergistic role between virus and host microRNAs in the regulation of angiogenesis of virus-associated cancer.
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- 2020
10. Influence and mechanism of miR-99a suppressing development of colorectal cancer (CRC) with diabetes mellitus (DM)
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Gongfa Wu, Jiahao Liu, Peixuan Zhu, Xutao Lin, Meijuan Lu, Longmei Cai, and Xiaona Zhang
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0301 basic medicine ,Colorectal cancer ,business.industry ,Cell growth ,medicine.disease ,digestive system diseases ,Metastasis ,Blot ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Downregulation and upregulation ,030220 oncology & carcinogenesis ,microRNA ,Cancer research ,medicine ,Immunohistochemistry ,Pharmacology (medical) ,business ,PI3K/AKT/mTOR pathway - Abstract
Objective This study aimed to identify the changes of miRNAs in colorectal cancer (CRC) complicated with diabetes mellitus (DM) (CRC + DM) tissues and their potential effects. Methods The changes of miRNAs in CRC + DM tissues were determined by miRNA microarray. The expression levels of miR-99a in 40 clinical specimens and 6 CRC cell lines were determined by qRT-PCR. The capacity for miR-99a to induce cell proliferation and invasion was examined with miR-99a-overexpressing HCT-116 cells. The relative mTOR mRNA and protein levels were determined by qRT-PCR and Western blotting, respectively, in HCT-116 cells transfected with miR-99a. The dual luciferase assay was performed to confirm the direct regulation of miR-99a on mTOR 3'-UTR. The HCT-116 cells were treated with 100 mg/L advanced glycation end products (AGEs); then, the mTOR expression levels were determined by qRT-PCR, Western blotting, and immunohistochemistry. Results Seventeen miRNAs were found to be differentially expressed among normal tissue, CRC tissue, and CRC with DM tissue, including 15 upregulated and 2 downregulated with fold changs of more than 2 times. qRT-PCR confirmed that miR-99a was downregulated in CRC and CRC + DM tissues. In addition, miR-99a overexpression remarkably impaired CRC cell proliferation and metastasis, and negatively regulated mTOR signaling through direct binding to the 3'-UTR of mTOR. AGEs could suppress miR-99a and stimulate mTOR signaling in CRC cells. Increased mTOR was also identified in CRC with DM tissues. Conclusion Our findings indicate that miR-99a is a potential marker and therapeutic target of CRC complicated with DM, and that AGEs impair miR-99a-overactivated mTOR signaling in CRC with DM patients, which promotes CRC development.
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- 2019
11. Dimethyl Fumarate Abrogates Growth and Metastasis of Hepatocellular Carcinoma by Regulating NRF2/Bcl-XL Axis and Synergizes with Sorafenib
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Oluwasijibomi Damola Faleti, Mingjiao Zhang, Haiqi Tan, Yibing Gong, Yuanbin Zhang, Simin Deng, Pengfei Liu, Jing Huang, Gongfa Wu, Xiong Wang, Ying Chen, Mingliang He, and Xiaoming Lyu
- Abstract
BackgroundEmerging evidence indicates that the mitochondria play an important role in poor treatment outcomes observed in liver malignancies. Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide, and there is still no effective chemotherapeutic treatment. Dimethyl fumarate (DMF), a derivative of fumaric acid, is used to treat psoriasis and multiple sclerosis. MethodsHCC mice model was used in this study. Eight-week-old mice bearing tumor were administered either DMF (30 mg/kg/day; n = 6) or DMSO (control group; n = 6) for 2 weeks. RNA-seq analysis was carried out on DMF-treated cells, and validation was done in two different HCC cell lines. Changes in subcellular structures were analyzed with electron microscopy. The expression of Bcl-xL, Nrf2, p-STAT3 and p-AKT were evaluated by immunoblotting.ResultsTumour growth of HCC was significantly lower in the DMF group compared to the control group (605.84 ± 65.06 mm3 and 232.1± 57.14 mm3, p < 0.01). Molecular and morphological studies revealed significant perturbation in the mitochondria accompanied by disruption of the NRF2/Bcl-xL axis. Enforced Bcl-xL expression in HCC cells markedly reversed DMF-induced apoptosis and induction of mesenchymal-to-epithelial transition. Notably, we also identified the activation of unfolded protein response as a potential marker for poor response. More strikingly, DMF synergistically enhanced sorafenib’s antitumor effect both in vitro, in zebrafish and mice xenograft models.ConclusionCollectively, our results demonstrate new mechanism insights into the antitumor effects of DMF and support the design of novel therapeutic options for HCC treatment.
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- 2021
12. Quantitative magnetic resonance imaging assessment of brain injury after successful cardiopulmonary resuscitation in a rat model of asphyxia cardiac arrest
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Zhifeng, Liu, Tangchun, Liu, Jinhui, Cai, Gongfa, Wu, Guangyi, Wang, Yue, Wang, Wanchun, Tang, Zhengfei, Yang, and Qingyu, Liu
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Asphyxia ,Disease Models, Animal ,Brain Injuries ,Animals ,Magnetic Resonance Imaging ,Cardiopulmonary Resuscitation ,Heart Arrest ,Rats - Abstract
The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted magnetic resonance imaging (DWI) to measure changes in blood-brain barrier (BBB) permeability and cerebral edema over time in a rat model of asphyxial cardiac arrest (ACA). ACA was established by endotracheal tube clamping. Male rats were randomized into a sham group (n = 5) and three ACA groups (n = 18). After return of spontaneous circulation (ROSC), the rats were randomized to perform DWI and DCE-MRI exam in the 6 h, 24 h and 72 h timepoint (ROSC + 6 h, ROSC + 24 h, and ROSC + 72 h). Results shows that fifteen of 18 animals achieved successful resuscitation in the ACA groups. The average apparent diffusion coefficient(ADC) value of the whole brain in ROSC + 6 h was markedly lower than those of the sham, ROSC + 24 h, and ROSC + 72 h. The aquaporin-4(AQP4) score in ROSC + 6 h was significantly higher than those in the other groups, which were negatively correlated with the ADC values. The ratio of whole brain to masseter muscle of volume transfer constant (rK
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- 2021
13. N-acetylcysteine alleviates post-resuscitation myocardial dysfunction and improves survival outcomes via partly inhibiting NLRP3 inflammasome induced-pyroptosis
- Author
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Qin Ling, Guanghui Zheng, Qiaohua Hu, Fenglian He, Longyuan Jiang, Jingying Hou, Jin Yang, Zhengfei Yang, Wanchun Tang, Hui Zhao, Gongfa Wu, and Yue Wang
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Resuscitation ,medicine.medical_treatment ,Clinical Biochemistry ,Ischemia ,Pharmacology ,Return of spontaneous circulation ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Pyroptosis ,medicine ,Cardiopulmonary resuscitation ,business.industry ,Research ,lcsh:RM1-950 ,Inflammasome ,Cell Biology ,medicine.disease ,N-acetylcysteine ,lcsh:Therapeutics. Pharmacology ,Ventricular fibrillation ,Myocardial function ,business ,Oxidative stress ,030215 immunology ,medicine.drug - Abstract
Background NOD-like receptor 3 (NLRP3) inflammasome is necessary to initiate acute sterile inflammation. Increasing evidence indicates the activation of NLRP3 inflammasome induced pyroptosis is closely related to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. N-acetylcysteine (NAC) is an antioxidant and plays a protective role in local myocardial I/R injury, while its effect on post-resuscitation myocardial dysfunction, as well as its mechanisms, remain elusive. In this study, we aimed to investigate the effect of NAC on post-resuscitation myocardial dysfunction in a cardiac arrest rat model, and whether its underlying mechanism may be linked to ROS and NLRP3 inflammasome-induced pyroptosis. Methods The rats were randomized into three groups: (1) sham group, (2) cardiopulmonary resuscitation (CPR) group, and (3) CPR + NAC group. CPR group and CPR + NAC group went through the induction of ventricular fibrillation (VF) and resuscitation. After return of spontaneous circulation (ROSC), rats in the CPR and CPR + NAC groups were again randomly divided into two subgroups, ROSC 6 h and ROSC 72 h, for further analysis. Hemodynamic measurements and myocardial function were measured by echocardiography, and western blot was used to detect the expression of proteins. Results Results showed that after treatment with NAC, there was significantly better myocardial function and survival duration; protein expression levels of NLRP3, adaptor apoptosis-associated speck-like protein (ASC), Cleaved-Caspase-1 and gasdermin D (GSDMD) in myocardial tissues were significantly decreased; and inflammatory cytokines levels were reduced. The marker of oxidative stress malondialdehyde (MDA) decreased and superoxide dismutase (SOD) increased with NAC treatment. Conclusions NAC improved myocardial dysfunction and prolonged animal survival duration in a rat model of cardiac arrest. Moreover, possibly by partly inhibiting ROS-mediated NLRP3 inflammasome-induced pryoptosis.
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- 2020
14. Influence and mechanism of miR-99a suppressing development of colorectal cancer (CRC) with diabetes mellitus (DM)
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Peixuan, Zhu, Jiahao, Liu, Meijuan, Lu, Gongfa, Wu, Xutao, Lin, Longmei, Cai, and Xiaona, Zhang
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diabetes mellitus ,mTOR ,colorectal cancer ,digestive system diseases ,miR-99a ,OncoTargets and Therapy ,Original Research - Abstract
Peixuan Zhu,1,* Jiahao Liu,2,* Meijuan Lu,1 Gongfa Wu,3 Xutao Lin,1 Longmei Cai,4 Xiaona Zhang1 1The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Pathology, Zengcheng District People’s Hospital of Guangzhou City, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Longmei CaiDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Avenue, Guangzhou 510515, People’s Republic of ChinaTel +86 206 278 7747Email cailongmeibestlove@163.comXiaona ZhangGraceland Medical Center The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Yuancun Er Heng Road, Guangzhou 510655, People’s Republic of ChinaTel +86 203 877 7688Email zhangxn33@mail.sysu.edu.cnObjective: This study aimed to identify the changes of miRNAs in colorectal cancer (CRC) complicated with diabetes mellitus (DM) (CRC+DM) tissues and their potential effects.Methods: The changes of miRNAs in CRC+DM tissues were determined by miRNA microarray. The expression levels of miR-99a in 40 clinical specimens and 6 CRC cell lines were determined by qRT-PCR. The capacity for miR-99a to induce cell proliferation and invasion was examined with miR-99a-overexpressing HCT-116 cells. The relative mTOR mRNA and protein levels were determined by qRT-PCR and Western blotting, respectively, in HCT-116 cells transfected with miR-99a. The dual luciferase assay was performed to confirm the direct regulation of miR-99a on mTOR 3′-UTR. The HCT-116 cells were treated with 100mg/L advanced glycation end products (AGEs); then, the mTOR expression levels were determined by qRT-PCR, Western blotting, and immunohistochemistry.Results: Seventeen miRNAs were found to be differentially expressed among normal tissue, CRC tissue, and CRC with DM tissue, including 15 upregulated and 2 downregulated with fold changs of more than 2 times. qRT-PCR confirmed that miR-99a was downregulated in CRC and CRC+DM tissues. In addition, miR-99a overexpression remarkably impaired CRC cell proliferation and metastasis, and negatively regulated mTOR signaling through direct binding to the 3′-UTR of mTOR. AGEs could suppress miR-99a and stimulate mTOR signaling in CRC cells. Increased mTOR was also identified in CRC with DM tissues.Conclusion: Our findings indicate that miR-99a is a potential marker and therapeutic target of CRC complicated with DM, and that AGEs impair miR-99a-overactivated mTOR signaling in CRC with DM patients, which promotes CRC development.Keywords: miR-99a, colorectal cancer, diabetes mellitus, mTOR
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- 2019
15. Quantitative CT assessment of lung injury after successful cardiopulmonary resuscitation in a porcine cardiac arrest model of different downtimes
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Wanchun Tang, Zhengfei Yang, Yue Wang, Rui Chen, Gongfa Wu, Zhifeng Liu, Qin Ling, Qingyu Liu, Cai Wen, and Hai-Gang Li
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Lung ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,030208 emergency & critical care medicine ,030204 cardiovascular system & hematology ,Lung injury ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Hounsfield scale ,Anesthesia ,Ventricular fibrillation ,medicine ,Breathing ,Arterial blood ,Original Article ,Radiology, Nuclear Medicine and imaging ,Cardiopulmonary resuscitation ,Quantitative computed tomography ,business - Abstract
Background: Utilize quantitative computed tomography (QCT) to detect and evaluate the severity of lung injury after successful cardiopulmonary resuscitation (CPR) in a porcine cardiac arrest (CA) model with different downtimes. Methods: Twenty-one male domestic pigs weighing 38±3 kg were randomized into 3 groups: the sham group (n=5), the ventricular fibrillation (VF) 5 min (VF5) group (n=8), and the VF 10 min (VF10) group (n=8). VF was induced and untreated for 5 (VF5 group) or 10 (VF10 group) min before the commencement of manual CPR. Eight animals (8/8, 100%) in VF5 and 6 (6/8, 75%) in VF10 were successfully resuscitated. Chest QCT scans and arterial blood gas tests were performed at baseline and 6 h post-resuscitation. The QCT score, volume, and weight of ground-glass opacification (GGO), which was defined as poorly aerated regions with a CT value ranging from −500 Hounsfield units (HU) to −100 HU, and intense parenchymal opacification (IPO), which was defined as a non-aerated area with a CT value greater than −100 HU, were quantitatively measured. Results: Significantly shorter durations of CPR and fewer defibrillations were observed in the VF5 group compared with the VF10 group [duration of CPR: VF5 (6±0 minutes) versus VF10 (8.3±1.5 minutes), P
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- 2018
16. EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma
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Yufei Long, Jing Huang, Oluwasijibomi Damola Faleti, Tielian Liu, Xiaoming Lyu, Qiang Jiang, Tuotuo Chong, Xin Li, Xu Yang, Jianguo Wang, Xia Guo, Pengfei Liu, Chi Man Tsang, Gongfa Wu, Ming-Liang He, Wang Qian, Sai Wah Tsao, and Yang Jiao
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0301 basic medicine ,Metabolic Processes ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Angiogenesis ,Physiology ,Protein Expression ,Cardiovascular Physiology ,Biochemistry ,Neovascularization ,Glucose Metabolism ,Medicine and Health Sciences ,Biology (General) ,Nasopharyngeal Carcinoma ,biology ,Neovascularization, Pathologic ,TOR Serine-Threonine Kinases ,Animal Models ,Nucleic acids ,Oncology ,Experimental Organism Systems ,Carbohydrate Metabolism ,RNA, Viral ,Hypoxia-Inducible Factor 1 ,medicine.symptom ,Glycolysis ,Research Article ,Signal Transduction ,QH301-705.5 ,Immunology ,Mouse Models ,Transfection ,Research and Analysis Methods ,Microbiology ,Carcinomas ,03 medical and health sciences ,Model Organisms ,Virology ,Cell Line, Tumor ,medicine ,otorhinolaryngologic diseases ,Genetics ,Gene Expression and Vector Techniques ,PTEN ,Humans ,Protein kinase A ,Molecular Biology Techniques ,Non-coding RNA ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Natural antisense transcripts ,Molecular Biology Assays and Analysis Techniques ,Adenylate Kinase ,PTEN Phosphohydrolase ,AMPK ,Biology and Life Sciences ,Cancers and Neoplasms ,Correction ,RC581-607 ,medicine.disease ,Gene regulation ,MicroRNAs ,030104 developmental biology ,Metabolism ,Nasopharyngeal carcinoma ,Anaerobic glycolysis ,biology.protein ,Cancer research ,Animal Studies ,RNA ,Parasitology ,Gene expression ,Immunologic diseases. Allergy ,Developmental Biology - Abstract
Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. The occurrence of both events involves many key molecular changes including miRNA. However, EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis. Here, we reported that one of the key miRNAs encoded by EBV, EBV-miR-Bart1-5P, can significantly promote nasopharyngeal carcinoma (NPC) cell glycolysis and induces angiogenesis in vitro and in vivo. Mechanistically, EBV-miR-Bart1-5P directly targets the α1 catalytic subunit of AMP-activated protein kinase (AMPKα1) and consequently regulates the AMPK/mTOR/HIF1 pathway which impelled NPC cell anomalous aerobic glycolysis and angiogenesis, ultimately leads to uncontrolled growth of NPC. Our findings provide new insights into metabolism and angiogenesis of NPC and new opportunities for the development of targeted NPC therapy in the future., Author summary The Epstein-Barr virus (EBV), the first reported human tumor virus found to encode miRNAs, which closely related to malignant progression of tumors. In our study, we have observed that EBV-miR-BART1-5P, an EBV-BARTs encoded miRNA, promotes glycolysis and induces angiogenesis in NPC. Interestingly, we showed that overexpression of EBV-miR -BART1-5P and restored PTEN at the same time, did not completely reverse the phenotypes of glycolysis, angiogenesis and proliferation, suggesting that EBV-miR-BART1-5P can mediate glycolysis and induction angiogenesis by a PTEN-independent manner. Further mechanism exploration demonstrated that EBV-miR-BART1-5P has important roles in cancer cell glucose metabolism and angiogenesis by inhibiting AMPKα1 and PTEN, which provides a molecular basis for the regulation of AMPK/mTOR/HIF1 and PTEN/FAK, Shc, AKT pathways, respectively.
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- 2018
17. Correlation of epithelial-mesenchymal transition and MACC1 in squamous cell carcinoma of tongue
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Haigang Li, Jing-Jing Han, Chen Chun, Yeqing Liu, Zhiquan Huang, Qing Sun, Gongfa Wu, and Chaobin Pan
- Subjects
medicine.anatomical_structure ,Chemistry ,Tongue ,Cancer research ,medicine ,Basal cell ,Epithelial–mesenchymal transition - Published
- 2016
18. [Expression of miR-200a in colorectal carcinoma cell lines and its effect on LoVo cells]
- Author
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Gongfa, Wu, Haiyan, Zhao, Nan, He, and Huixia, Han
- Subjects
Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cell Line, Tumor ,Down-Regulation ,Humans ,Apoptosis ,Colorectal Neoplasms ,Transfection ,Cell Proliferation - Abstract
To detect miR-200a expression in human colorectal carcinnoma (CRC) cell lines and explore the role of miR-200a in regulating the biological behavior of CRC cells.Real-time quantitative RT-PCR (qRT-PCR) was used to detect miR-200a expression levels in 6 CRC cell lines (HCT116, HT29, LS174T, SW480, SW620 and LoVo). miR-200a mimics were transiently transfected into LoVo, and the changes in cell proliferation, apoptosis, migration, and cell-cell adhesion were assessed using CCK-8 assay, TUNEL assay, transwell migration assay, and homogenous adhesion experiment, respectively.The expression of miR-200a was down-regulated in the 6 CRC cell lines, among which the highly metastatic LoVo cell line showed the lowest expression and the tumorigenic but non-metastatic CRC cell line HCT116 had the highest expression. Overexpression of miR-200a depressed cell proliferation and migration but promoted cell apoptosis and cell-cell adhesion in LoVo cells.miR-200a plays a role in regulating the invasiveness and metastasis of CRC, and overexpression of miR-200a causes a significant reduction of cell proliferation and migration and promotes apoptosis and cell-cell adhesion in LoVo cells.
- Published
- 2015
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