14 results on '"Yang, Weiwei"'
Search Results
2. A circular RNA from NFIX facilitates oxidative stress-induced H9c2 cells apoptosis.
- Author
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Cui X, Dong Y, Li M, Wang X, Jiang M, Yang W, Liu G, Sun S, and Xu W
- Subjects
- Animals, Cell Line, Male, Mice, Inbred C57BL, RNA, Circular genetics, Apoptosis genetics, Oxidative Stress genetics, RNA, Circular metabolism
- Abstract
Myocardial infarction is the leading cause of death worldwide, and cardiomyocyte apoptosis during myocardial infarction and reperfusion is a significant factor of poor prognosis. As important regulatory molecules, biofunctions of circRNAs in the pathogenesis of myocardial infarction remain elusive. To confirm the expression level and biological function of circNFIX in cardiomyocytes upon oxidative stress. Divergent polymerase chain reaction and Sanger sequencing were performed to verify the circular structure. The stability of circNFIX was confirmed by RNase R treatment and actinomycin D assay. In order to simulate oxidative stress during myocardial infarction, H9c2 cells were subjected to hydrogen peroxide and hypoxia stimulation. In vivo, mouse models of myocardial ischemia were established. The biological function of circNFIX in cardiomyocytes was investigated through loss- and gain-of-function assays, and cardiomyocyte apoptosis level was detected by the terminal deoxyribonucleotidyl transferase-mediated TdT-mediated dUTP nick end labeling assay and Western blot. CircNFIX is abundant, conserved, and stable in H9c2 cells. The expression of circNFIX was significantly downregulated in cardiomyocytes subjected to oxidative stress. Enforced CircNFIX promotes H9c2 cells apoptosis induced by hydrogen peroxide, in sharp contrast to circNFIX knockdown. In this study, we found that circNFIX served as a pro-apoptosis factor in cardiomyocyte apoptosis. CircNFIX possesses potential to be the biomarker and therapeutic target in myocardial infarction.
- Published
- 2020
- Full Text
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3. N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo.
- Author
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Xie H, Li X, Yang W, Yu L, Jiang X, Chen Y, Shen Z, Li C, Gu M, and Shi L
- Subjects
- Adenosine chemistry, Adenosine pharmacology, Animals, Calcium metabolism, Cell Line, Tumor, Cell Proliferation drug effects, HEK293 Cells, Humans, Membrane Potential, Mitochondrial drug effects, Mice, Nude, Reactive Oxygen Species metabolism, Stomach Neoplasms ultrastructure, Adenosine analogs & derivatives, Apoptosis drug effects, Autophagy drug effects, Endoplasmic Reticulum Stress drug effects, Stomach Neoplasms pathology
- Abstract
Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca
2+ -related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.- Published
- 2020
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4. Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways.
- Author
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Zhang Y, Zhang L, Fan X, Yang W, Yu B, Kou J, and Li F
- Subjects
- Animals, Aorta drug effects, Aorta pathology, Blotting, Western, Enzyme-Linked Immunosorbent Assay, In Situ Nick-End Labeling, Janus Kinase 2 metabolism, Male, Mice, Mice, Inbred C57BL, Myocardium pathology, STAT3 Transcription Factor metabolism, Signal Transduction drug effects, Wnt3A Protein metabolism, beta Catenin metabolism, Angiotensin-Converting Enzyme Inhibitors pharmacology, Apoptosis drug effects, Captopril pharmacology, Heart Failure prevention & control
- Abstract
Captopril (Cap) as angiotensin-converting enzyme inhibitor (ACEi) is commonly used to treat hypertension and some types of congestive heart failure. However, few studies reported on whether Cap exerts a protective effect on myocardial apoptosis induced by transverse aortic constriction (TAC). This study aimed at investigating the possible mechanism of Cap on myocardial apoptosis induced by pressure overload. Results showed that Cap significantly decreased heart-to-body weight ratios (HBWR). Cap markedly improved cardiac function, and reduced inner diameter of ascending aorta (Asc Ao) in TAC mice as shown by echocardiography. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that Cap treatment also markedly decreased the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cardiac pathological changes and fibrosis have been improved after Cap treatment as shown by hematoxylin-eosin (H&E) staining and Masson's trichrome staining. Moreover, Terminal deoxynucleotidyl transferase-mediated dexoxyuridine triphosphate nick-end labeling (TUNEL) staining result indicated Cap treatment also significantly inhibited cardiac apoptosis. Western Blot results showed that Cap obviously decreased the expression of cleaved capase-3, Bax, phosphorylated Jak2 (p-Jak2), phosphorylated Stat3 (p-Stat3), Wnt3a and β-catenin proteins, as well as increased Bcl-2 expression. In conclusion, Cap showed a protective effect on TAC-induced cardiac apoptosis, which could be attributed to the inhibition of Wnt3a/β-catenin signaling pathway. Cap also attenuated myocardial hypertrophy induced by TAC via suppression of Jak2/Stat3 pathway., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2019
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5. [MALAT1 inhibits proliferation and promotes apoptosis of SH-SY5Y cells induced by Aβ 25-35 via blocking PI3K/mTOR/GSK3β pathway].
- Author
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Yang W, Zhang S, Li B, and Zhang Y
- Subjects
- Amyloid beta-Peptides, Cell Line, Tumor, Gene Knockdown Techniques, Glycogen Synthase Kinase 3 beta, Humans, Peptide Fragments, Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases, Apoptosis, Cell Proliferation, RNA, Long Noncoding genetics, Signal Transduction
- Abstract
Objective To investigate the effects of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on cell cycle, proliferation and apoptosis in SH-SY5Y model cells of Alzheimer's disease (AD). Methods The AD model cells (SH-SY5Y human neuroblastoma cells) were constructed using Aβ
25-35 . The AD cells were randomly divided into five groups: control group, over-expressed empty victor (pCDH-EV) group, MALAT1 over-expression (pCDH-MALAT1) group, MALAT1 expression inhibition of empty victor (pSICOR-EV) group, and MALAT1 expression inhibition (pSICOR-shMALAT1) group. The cell proliferation activity of all the groups was detected by MTT assay. The cell cycle and apoptosis rate were detected by flow cytometry after 48 hours of transfection. Western blot analysis was used to test the expressions of BAX, Bcl-2, caspase-3 and PI3K/mTOR/GSK3β proteins in the five groups. Results The AD model cells, over-expression and inhibition expression of MALAT1 vectors were successfully constructed. Inhibited expression of MALAT1 significantly inhibited the proliferation of AD SH-SY5Y cells, promoted apoptosis and arrested cell cycle in G1 phase. Western blotting showed that the inhibited expression of MALAT1 up-regulated the expressions of BAX, caspase-3 and down-regulated the expression of Bcl-2. At the same time, the inhibited expression of MALAT1 significantly inhibited the expression of p-PI3K/p-mTOR/p-GSK3β. In addition, over-expression of MALAT1 reversed the above effects. Conclusion Konck-down of MALAT1 can inhibit the proliferation and promote the apoptosis of AD model cells via down-regulating the activity of PI3K/mTOR/GSK3β.- Published
- 2018
6. Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2.
- Author
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Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, Li C, Yang F, Zeng R, Wei P, Li D, Li W, and Yang W
- Subjects
- Amino Acid Sequence, Carcinogenesis metabolism, Carcinogenesis pathology, Cell Line, Tumor, Cullin Proteins metabolism, Glioma metabolism, Glioma pathology, HSP90 Heat-Shock Proteins metabolism, Humans, Hydrogen Peroxide pharmacology, Mitochondria drug effects, Phosphorylation drug effects, Phosphothreonine metabolism, Prognosis, Protein Binding drug effects, Protein Stability drug effects, Protein Transport drug effects, Proteolysis drug effects, Pyruvate Kinase chemistry, Ubiquitin-Protein Ligases metabolism, Apoptosis drug effects, Mitochondria metabolism, Oxidative Stress drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Pyruvate Kinase metabolism
- Abstract
Pyruvate kinase M2 isoform (PKM2) catalyzes the last step of glycolysis and plays an important role in tumor cell proliferation. Recent studies have reported that PKM2 also regulates apoptosis. However, the mechanisms underlying such a role of PKM2 remain elusive. Here we show that PKM2 translocates to mitochondria under oxidative stress. In the mitochondria, PKM2 interacts with and phosphorylates Bcl2 at threonine (T) 69. This phosphorylation prevents the binding of Cul3-based E3 ligase to Bcl2 and subsequent degradation of Bcl2. A chaperone protein, HSP90α1, is required for this function of PKM2. HSP90α1's ATPase activity launches a conformational change of PKM2 and facilitates interaction between PKM2 and Bcl2. Replacement of wild-type Bcl2 with phosphorylation-deficient Bcl2 T69A mutant sensitizes glioma cells to oxidative stress-induced apoptosis and impairs brain tumor formation in an orthotopic xenograft model. Notably, a peptide that is composed of the amino acid residues from 389 to 405 of PKM2, through which PKM2 binds to Bcl2, disrupts PKM2-Bcl2 interaction, promotes Bcl2 degradation and impairs brain tumor growth. In addition, levels of Bcl2 T69 phosphorylation, conformation-altered PKM2 and Bcl2 protein correlate with one another in specimens of human glioblastoma patients. Moreover, levels of Bcl2 T69 phosphorylation and conformation-altered PKM2 correlate with both grades and prognosis of glioma malignancy. Our findings uncover a novel mechanism through which mitochondrial PKM2 phosphorylates Bcl2 and inhibits apoptosis directly, highlight the essential role of PKM2 in ROS adaptation of cancer cells, and implicate HSP90-PKM2-Bcl2 axis as a potential target for therapeutic intervention in glioblastoma.
- Published
- 2017
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7. Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner.
- Author
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Wang T, Han P, He Y, Zhao C, Wang G, Yang W, Shan M, Zhu Y, Yang C, Weng M, Wu D, Gao L, Jin X, Wei Y, Cui B, Shen G, and Li X
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma pathology, Adult, Aged, Apoptosis drug effects, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, DNA Repair drug effects, Drug Resistance, Neoplasm, Female, HCT116 Cells, Histones biosynthesis, Histones genetics, Humans, Male, MicroRNAs physiology, Middle Aged, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, RNA, Neoplasm physiology, RNA-Binding Proteins biosynthesis, RNA-Binding Proteins genetics, Recombinant Fusion Proteins biosynthesis, Recombinant Fusion Proteins genetics, Single-Blind Method, Adenocarcinoma drug therapy, Antimetabolites, Antineoplastic pharmacology, Apoptosis genetics, Colonic Neoplasms drug therapy, Fluorouracil pharmacology, Neoplasm Proteins physiology, RNA-Binding Proteins physiology
- Abstract
RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.
- Published
- 2016
- Full Text
- View/download PDF
8. Developmental and activity-dependent expression of LanCL1 confers antioxidant activity required for neuronal survival.
- Author
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Huang C, Chen M, Pang D, Bi D, Zou Y, Xia X, Yang W, Luo L, Deng R, Tan H, Zhou L, Yu S, Guo L, Du X, Cui Y, Hu J, Mao Q, Worley PF, and Xiao B
- Subjects
- Animals, Brain cytology, Brain embryology, Brain metabolism, Gene Deletion, Gene Expression Regulation, Developmental, Mice, Mice, Inbred C57BL, Mitochondria metabolism, Neurons physiology, Oxidative Stress, Receptors, G-Protein-Coupled genetics, Apoptosis, Neurons metabolism, Reactive Oxygen Species metabolism, Receptors, G-Protein-Coupled metabolism
- Abstract
Production of reactive oxygen species (ROS) increases with neuronal activity that accompanies synaptic development and function. Transcription-related factors and metabolic enzymes that are expressed in all tissues have been described to counteract neuronal ROS to prevent oxidative damage. Here, we describe the antioxidant gene LanCL1 that is prominently enriched in brain neurons. Its expression is developmentally regulated and induced by neuronal activity, neurotrophic factors implicated in neuronal plasticity and survival, and oxidative stress. Genetic deletion of LanCL1 causes enhanced accumulation of ROS in brain, as well as development-related lipid, protein, and DNA damage; mitochondrial dysfunction; and apoptotic neurodegeneration. LanCL1 transgene protects neurons from ROS. LanCL1 protein purified from eukaryotic cells catalyzes the formation of thioether products similar to glutathione S-transferase. These studies reveal a neuron-specific glutathione defense mechanism that is essential for neuronal function and survival., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
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9. Swimming prevents cell death of chondrocytes via PI3K/AKT pathway in an experimental model.
- Author
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Qian, Jiajia, Zhao, Peiru, Xu, Qi, Yang, Weiwei, and Cai, Ren
- Subjects
KNEE osteoarthritis ,CARTILAGE cells ,EXPERIMENTAL design ,AUTOPHAGY ,ANTERIOR cruciate ligament ,IMMUNOHISTOCHEMISTRY ,WESTERN immunoblotting ,CELLULAR signal transduction ,DESCRIPTIVE statistics ,RESEARCH funding ,SWIMMING ,CELL death ,ANIMALS ,MICE ,OLD age - Abstract
Background: Knee Osteoarthritis (KOA) is one of the main causes of disability in the elderly and with limited treatment options. Swimming was considered as an ideal form of non-surgical management of KOA. Nevertheless, the mechanism of swimming intervene OA remains unclear. ACLT induced OA model was often used to study the pathogenesis and treatment of OA. Thus, we evaluated the protective effect of swimming on KOA mouse and tried to explore the underlying mechanism. Methods: Forty C57BL/6 mice were randomly divided into five groups: Blank group, ACLT group, ACLT + Swim group, Sham group and Sham + Swim group (n = 8). OA model was established by Anterior Cruciate Ligament Transection surgery (ACLT). After modeling, mice in ACLT + Swim and Sham + Swim groups were trained with a moderate swimming program, 5 d/week, for 6 weeks. HE and Safranin-O/fast staining, Immunohistochemistry, TUNEL assay and Western blot were used to detect the effect of swimming on pathological changes, cell death and the mechanism in KOA mouse. Results: Swimming significantly enhanced CoII expression and suppressed ADAMTS5 expression in cartilage of KOA mouse, thus ameliorated KOA development. Apoptotic and autophagic processes were enhanced in OA cartilage, which might be caused by down-regulation of PI3K/AKT pathway; swimming could activate PI3K/AKT pathway and thus regulate apoptosis and autophagy processes of chondrocytes. Conclusion: Swimming could prevent cell death of chondrocytes via PI3K/AKT pathways, thus delayed the progression of KOA in an experimental model. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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10. Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway.
- Author
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Meng, Xiangrui, Wang, Huijuan, Zhao, Jingzhu, Hu, Linfei, Zhi, Jingtai, Wei, Songfeng, Ruan, Xianhui, Hou, Xiukun, Li, Dapeng, Zhang, Jun, Yang, Weiwei, Qian, Biyun, Wu, Yu, Zhang, Yuan, Meng, Zhaowei, Guan, Lizhao, Zhang, Huilai, Zheng, Xiangqian, and Gao, Ming
- Subjects
IODINE isotopes ,PAPILLARY carcinoma ,THYROID cancer ,VASCULAR endothelial growth factors ,CELL proliferation ,SMALL interfering RNA - Abstract
Background: Patients with metastatic radioiodine-refractory papillary thyroid carcinoma (PTC) have limited treatment options and a poor prognosis. There is an urgent need to develop new drugs targeting PTC for clinical application. Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is highly selective for vascular endothelial growth factor receptor-2 (VEGFR2) and exhibits antitumor effects in a variety of solid tumors. Although apatinib has been shown to be safe and efficacious in radioiodine-refractory differentiated thyroid cancer, the mechanism underlying its antitumor effect is unclear. In this report, we explored the effects of apatinib on PTC in vitro and in vivo. Methods: VEGFR2 expression levels were evaluated by immunohistochemistry (IHC), qPCR, and western blotting (WB). The effects of apatinib on cell viability, colony formation, and migration in the Transwell assay were assessed in vitro , and its effect on tumor growth rate was assessed in vivo. In addition, the levels of proteins in signaling pathways were determined by WB. Finally, the autophagy level was assessed by WB, immunofluorescence (IF), and transmission electron microscopy. Results: We found that high VEGFR2 expression is associated with tumor size, T stage, and lymph node metastasis in patients with PTC and that apatinib inhibits PTC cell growth, promotes apoptosis, and induces cell cycle arrest through the PI3K/Akt/mTOR signaling pathway. Moreover, apatinib induces autophagy, and pharmacological inhibition of autophagy or small interfering RNA (siRNA)-mediated targeting of autophagy-associated gene 5 (ATG5) can further increase PTC cell apoptosis. Conclusion: Our data suggest that apatinib can induce apoptosis and autophagy via the PI3K/Akt/mTOR signaling pathway for the treatment of PTC and that autophagy is a potential novel target for future therapy in resistant PTC. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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11. Keratinocyte growth factor binding to fibroblast growth factor receptor 2-IIIb promotes epithelial ovarian cancer cell proliferation and invasion.
- Author
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Wu, Jun, Han, Wei, Yang, Weiwei, Liu, Hongyu, Li, Chunhong, Guo, Ling, Jin, Yan, Zhang, Ruijie, and Chen, He
- Subjects
KERATINOCYTE growth factors ,FIBROBLAST growth factor 2 ,OVARIAN cancer ,CANCER cells ,IMMUNOHISTOCHEMISTRY ,MONOCLONAL antibodies ,APOPTOSIS ,CELL physiology ,CELL receptors ,CELL motility ,CELLULAR signal transduction ,GROWTH factors ,OVARIAN tumors ,PHOSPHORYLATION ,PROGNOSIS ,PROTEINS ,TUMORS ,ENDOMETRIAL tumors ,CASE-control method ,CANCER cell culture - Abstract
Aim Of Study: To analyze the function of keratinocyte growth factor (KGF) and it ligand fibroblast growth factor receptor 2-IIIb (FGFR2-IIIb) in the epithelial ovarian cancer (EOC) progression.Materials and Methods: In this study, the protein KGF and corresponding ligand FGFR2-IIIb expression were detected in both normal epithelial ovarian tissues and in EOC tissues. Seventy-one ovarian tumor tissues were examined for KGF and FGFR2-IIIb expression by immunohistochemistry; seven normal epithelial ovarian tissues as control were examined. By using a monoclonal antibody to inhibit KGF activation, we tested KGF-induced EOC cells invasion ability. By means of Western blot, we tested extracellular signal-regulated kinase (ERK), phosphorylation ERK, myosin light chain (MLC), and phosphorylation MLC with or without KGF protein.Results: We found that the expression FGFR2-IIIb increased in EOC cells and tissues comparing with its normal counterpart, and the expression of KGF protein decreased or undetectable in human EOC cells and tissues comparing with its normal part. The effect of KGF in promoting EOC cell invasion was blocked by an FGFR2-IIIb antibody. We further discovered that KGF upregulated ERK and MLC phosphorylation in the highly invasive ovarian cancer cell line HO8910PM. Therefore, regarding the highly invasive ovarian cancer cells, we speculated that KGF might promote proliferation and invasion through the ERK-MLC pathway.Conclusions: These results suggest that KGF might play an important role in the progression of ovarian cancer and could be an attractive target for ovarian cancer therapy. [ABSTRACT FROM AUTHOR]- Published
- 2018
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12. Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner.
- Author
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Wang, Tianzhen, Han, Peng, He, Yan, Zhao, Ci, Wang, Guangyu, Yang, Weiwei, Shan, Ming, Zhu, Yuanyuan, Yang, Chao, Weng, Mingjiao, Wu, Di, Gao, Lin, Jin, Xiaoming, Wei, Yunwei, Cui, BinBin, Shen, Guomin, and Li, Xiaobo
- Abstract
RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
13. Dihydroartemisinin suppresses STAT3 signaling and Mcl-1 and Survivin expression to potentiate ABT-263-induced apoptosis in Non-small Cell Lung Cancer cells harboring EGFR or RAS mutation.
- Author
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Yan, Xiaohui, Li, Pengfei, Zhan, Yihong, Qi, Miao, Liu, Jin, An, Zhifeng, Yang, Weiwei, Xiao, Hui, Wu, Hongmei, Qi, Yitao, and Shao, Huanjie
- Subjects
- *
SURVIVIN (Protein) , *PROTEIN expression , *APOPTOSIS , *NON-small-cell lung carcinoma , *EPIDERMAL growth factor receptors - Abstract
Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide. A significant fraction of NSCLC carries activating mutations in epidermal growth factor receptor (EGFR) or RAS oncogene. Dihydroartemisinin (DHA) is a semisynthetic derivative of the herbal antimalarial drug artemisinin that has been recently reported to exhibit anti-cancer activity. To develop new therapeutic strategies for NSCLC, we investigated the interactions between DHA and ABT-263 in NSCLC cells harboring EGFR or RAS mutation. Our data indicated that DHA synergized with ABT-263 to trigger Bax-dependent apoptosis in NSCLC cells in culture. DHA treatment antagonized ABT-263-induced Mcl-1 upregulation and sensitized NSCLC cells to ABT-263-triggered apoptosis. Additionally, DHA treatment caused downregulation of Survivin and upregulation of Bim, which also contribute to cotreatment-induced cytotoxicity. Moreover, DHA effectively suppressed STAT3 phosphorylation, and STAT3 inactivation resulted in the downregulation of Mcl-1 and Survivin, functioning to enhance ABT-263-induced cytotoxicity. Finally, cotreatment of DHA and ABT-263 significantly inhibited xenograft growth in nude mice. Together, DHA effectively inhibits STAT3 activity and modulates expression of Mcl-1, Survivin and Bim, thereby synergizing with ABT-263 to trigger apoptosis in NSCLC cells harboring EGFR or RAS mutation. Our data provide a novel therapeutic strategy for EGFR or RAS mutant NSCLC treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
14. Hypoxic preconditioning induced neuroprotection against cerebral ischemic injuries and its cPKCγ-mediated molecular mechanism
- Author
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Zhang, Nan, Yin, Yanling, Han, Song, Jiang, Jun, Yang, Weiwei, Bu, Xiangning, and Li, Junfa
- Subjects
- *
CEREBRAL ischemia , *PROTEIN kinase C , *PROTEOMICS , *NERVE tissue proteins , *CELLULAR signal transduction , *WESTERN immunoblotting , *APOPTOSIS - Abstract
Abstract: As of yet, pharmacological treatments of stroke are only met with mediocre results, which are either ineffective or confounded by adverse effects, thus calling for a better understanding of endogenous neuroprotective mechanism. Previously, we have demonstrated that the translocated activation of conventional protein kinase Cγ (cPKCγ) is involved in the development of cerebral hypoxic preconditioning (HPC), one of the most profound neuroprotective strategies. This study was designed to substantiate the role of cPKCγ and its signaling molecules in HPC-induced neuroprotection against subsequent middle cerebral artery occlusion (MCAO)-induced permanent cerebral ischemic injuries. The effects of HPC and cPKCγ on cerebral ischemic injuries were studied by observing the changes in neurological deficits, infarct volume and neural cell apoptosis. cPKCγ membrane translocation (activation) and its interacting protein synapsin in the ischemic brain were examined by Western blot analysis. Proteomic approaches were employed to identify the cPKCγ-interacting proteins. We found that HPC could markedly attenuate MCAO-induced brain injuries and the decrease of cPKCγ membrane translocation, but cPKCγ inhibitor Go6983 could block HPC-induced neuroprotection. Among the 41 identified cPKCγ-interacting proteins, 17 up- and 6 down-regulated proteins were observed in cytosol or particulate fraction during HPC. In addition, the up-regulated synapsin could reciprocally co-precipitate with cPKCγ both in cytosol and particulate fractions, and Go6983 abolished HPC-induced inhibition on synapsin dephosphorylation in ischemic core and peri-infarct region (penumbra). This study is the first to report multiple cPKCγ-interacting proteins in HPC mouse brain and suggested that cPKCγ signaling molecules, especially the cPKCγ-synapsin pathway, might be responsible for HPC-induced neuroprotection against cerebral ischemic injuries of mice. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
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