共查询到20条相似文献，搜索用时 0 毫秒
1.
Qi Zhang Tianfu Li Zhecun Wang Xiaying Kuang Nan Shao Ying Lin 《Journal of cellular and molecular medicine》2020,24(14):8236-8247
Long non‐coding RNAs (lncRNAs) take various effects in cancer mostly through sponging with microRNAs (miRNAs). lncRNA NR2F1‐AS1 is found to promote tumour progression in hepatocellular carcinoma, endometrial cancer and thyroid cancer. However, the role of lncRNA NR2F1‐AS1 in breast cancer angiogenesis remains unknown. In this study, we found lncRNA NR2F1‐AS1 was positively related with CD31 and CD34 in breast cancer through Pearson's correlation analysis, while lncRNA NR2F1‐AS1 transfection promoted human umbilical vascular endothelial cell (HUVEC) tube formation. In breast cancer cells, lncRNA NR2F1‐AS1 enhanced the HUVEC proliferation, tube formation and migration ability through tumour‐conditioned medium (TCM). In zebrafish model, lncRNA NR2F1‐AS1 increased the breast cancer cell‐related neo‐vasculature and subsequently promoted the breast cancer cell metastasis. In mouse model, lncRNA NR2F1‐AS1 promoted the tumour vessel formation, increased the micro vessel density (MVD) and then induced the growth of primary tumour. Mechanically, lncRNA NR2F1‐AS1 increased insulin‐like growth factor‐1 (IGF‐1) expression through sponging miRNA‐338‐3p in breast cancer cells and then activated the receptor of IGF‐1 (IGF‐1R) and extracellular signal‐regulated kinase (ERK) pathway in HUVECs. These results indicated that lncRNA NR2F1‐AS1 could promote breast cancer angiogenesis through IGF‐1/IGF‐1R/ERK pathway. 相似文献
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Cheng Lu Bing Jiang Jie Xu Xuan Zhang Nianxin Jiang 《Journal of biochemical and molecular toxicology》2023,37(8):e23398
Acute myocardial infarction is regarded as myocardial necrosis resulting from myocardial ischemia/reperfusion (I/R) damage and retains a major cause of mortality. Neferine, which was extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., has been reported to possess a broad range of biological activities. However, its underlying mechanism on the protective effect of I/R has not been fully clarified. A hypoxia/reoxygenation (H/R) model with H9c2 cells closely simulating myocardial I/R injury was used as a cellular model. This study intended to research the effects and mechanism underlying neferine on H9c2 cells in response to H/R stimulation. Cell Counting Kit-8 and lactate dehydrogenase (LDH) release assays were employed to measure cell viability and LDH, respectively. Apoptosis and reactive oxygen species (ROS) were determined by flow cytometry analysis. Oxidative stress was evaluated by detecting malondialdehyde, superoxide dismutase, and catalase. Mitochondrial function was assessed by mitochondrial membrane potential, ATP content, and mitochondrial ROS. Western blot analysis was performed to examine the expression of related proteins. The results showed that hypoxia/reoxygenation (H/R)-induced cell damage, all of which were distinctly reversed by neferine. Moreover, we observed that neferine inhibited oxidative stress and mitochondrial dysfunction induced by H/R in H9c2 that were concomitant with increased sirtuin-1 (SITR1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 expression. On the contrary, silencing the SIRT1 gene with its small interferingRNA eliminated the beneficial effects of neferine. It is concluded that neferine preconditioning attenuated H/R-induced cardiac damage via suppressing apoptosis, oxidative stress, and mitochondrial dysfunction, which may be partially ascribed to the activation of SIRT1/Nrf2 signaling pathway. 相似文献
3.
Esther Imperlini Sara Spaziani Annamaria Mancini Marianna Caterino Pasqualina Buono Stefania Orrù 《Proteomics》2015,15(11):1813-1818
The abuse of mixed or combined performance‐enhancing drugs is widespread among athletes and amateurs, adults and adolescents. Clinical studies demonstrated that misuse of these doping agents is associated with serious adverse effects to many organs in human. Previously, we demonstrated in human peripheral blood lymphocytes that high doses of anabolic androgenic steroids, such as dihydrotestosterone (DHT) and growth factors, such as insulin‐like growth factor‐1 (IGF‐1), have effects at gene and protein levels. Supraphysiological treatments of DHT and IGF‐1 affected the expression of genes involved in skeletal muscle disorders as well as in cell‐mediated immunological response. At protein level, DHT hyperdosage affects cell motility and apoptosis; IGF‐1 hyperstimulation triggers an active cytoskeletal reorganization and an overproduction of immune response‐ and inflammation‐related cytokines. In this study, we investigate the combined effects of DHT and IGF‐1 hyperdosage in peripheral blood lymphocytes using a differential proteomic approach. DHT and IGF‐1 combined treatment affects cell adhesion, migration, and survival through modulation of expression levels of cytokines and paxillin‐signaling‐related proteins, and activation of several pathways downstream focal adhesion kinase. Our results indicate a synergistic effect of DHT and IGF‐1 which has potential implications for health risk factors. 相似文献
4.
Chao Wan Qiang Zhao Lianfang Zhang Qi Zhou Lianfu Deng 《Cell biochemistry and function》2012,30(4):297-302
Insulin and insulin‐like growth factor 1 (IGF‐1) are evolutionarily conserved hormonal signalling molecules, which influence a wide array of physiological functions including metabolism, growth and development. Using genetic mouse studies, both insulin and IGF‐1 have been shown to be anabolic agents in osteoblasts and bone development primarily through the activation of Akt and ERK signalling pathways. In this study, we examined the temporal signalling actions of insulin and IGF‐1 on primary calvarial osteoblast growth and differentiation. First, we observed that the IGF‐1 receptor expression decreases whereas insulin receptor expression increases during osteoblast differentiation. Subsequently, we show that although both insulin and IGF‐1 promote osteoblast differentiation and mineralization in vitro, IGF‐1, but not insulin, can induce osteoblast proliferation. The IGF‐1‐induced osteoblast proliferation was mediated via both MAPK and Akt pathways because the IGF‐1‐mediated cell proliferation was blocked by U0126, an MEK/MAPK inhibitor, or LY294002, a PI3‐kinase inhibitor. Osteocalcin, an osteoblast‐specific protein whose expression corresponds with osteoblast differentiation, was increased in a dose‐ and time‐dependent manner after insulin treatment, whereas it was decreased with IGF‐1 treatment. Moreover, insulin treatment dramatically induced osteocalcin promoter activity, whereas IGF‐1 treatment significantly inhibited it, indicating direct effect of insulin on osteocalcin synthesis. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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Nicklin LT Robinson RS Marsters P Campbell BK Mann GE Hunter MG 《Molecular reproduction and development》2007,74(6):724-729
In cattle, leptin has been implicated in the control of ovarian function and has been shown to modulate steroid production by theca and granulosa cells in a number of species. However, a direct effect of leptin on bovine luteal function has not been demonstrated. This study was conducted to determine if the leptin receptor (OB-R) is expressed in the bovine corpus luteum (CL), and to examine the effects of leptin on progesterone production by dispersed luteal cells in vitro. RT-PCR was used to detect the presence of OB-R and, more specifically, the long, biologically active isoform (OB-Rb), in CL, collected on days 2-18 of the oestrous cycle (n=18). The effects of leptin on progesterone production were investigated in dispersed luteal cells prepared from CL collected on days 5 and 8 (n=14) of the cycle. The dispersed luteal cells were cultured for 24 hr with recombinant human leptin and/or LR3-IGF-1 and/or LH. OB-Rs, in particular, OB-Rb, were expressed in the CL at all stages of development. Progesterone production by luteal cells was increased (P<0.001) by treatment with LH (10 ng/ml) but treatment with leptin alone had no effect. However, in the presence of IGF-1 (100 ng/ml), leptin (10 ng/ml) caused a significant (P<0.005) increase in progesterone production. In conclusion, we have shown that the leptin receptor is expressed in the bovine CL and have demonstrated a modulatory effect of leptin on luteal progesterone production in vitro. 相似文献
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Gabillard JC Duval H Cauty C Rescan PY Weil C Le Bail PY 《Molecular reproduction and development》2003,64(1):32-40
The Growth hormone (GH)/insulin-like growth factor (IGF) system promotes embryonic growth in higher vertebrates. Such a system exists in salmonids, but exhibits an additional level of complexity resulting from a recent whole genome tetraploidisation. Thus, two nonallelic GH genes are present in the trout genome. Although the two GH genes are similar, the possibility remains that the two genes have evolved separately, acquiring a distinct expression pattern. In this study, using whole mounted in situ hybridisation, we observed a one stage delay between the appearance of GH-2 (Stage 22) and GH-1 (Stage 23) soon after pituitary formation (Stage 21). In addition, by double in situ hybridisation, we clearly evidenced two types of somatotroph, one expressing only GH-2 and the other type both GH-1 and GH-2 at Stage 24. Consequently, at this stage more cells expressed GH-2 than GH-1 as confirmed by quantitative RT-PCR. However at hatching, as in adult, the difference between the expression of the two GH genes was no longer observed. In addition, our immunohistochemical studies did not show any delay between the expression of the mRNA and its translation as a protein at Stage 24. A comparison of the expression pattern of the IGF system components (IGF-1, IGF-2, and the receptor type I) determined by real time RT-PCR, have shown an IGF-1 mRNA increase concomitantly to the appearance of GH expression. On the whole, our results demonstrate a differential regulation of GH-1 and GH-2 genes in rainbow trout embryo. The relationship observed between the expression of different component of the GH/IGF system seems to indicate that this system could be functional early on during embryonic development. 相似文献
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Lynn H. H. Aung Ruibei Li Bellur S. Prabhakar Peifeng Li 《Journal of cellular and molecular medicine》2017,21(12):3394-3404
The long‐term usage of doxorubicin (DOX) is largely limited due to the development of severe cardiomyopathy. Many studies indicate that DOX‐induced cardiac injury is related to reactive oxygen species generation and ultimate activation of apoptosis. The role of novel mitochondrial fission protein 1 (Mtfp1) in DOX‐induced cardiotoxicity remains elusive. Here, we report the pro‐mitochondrial fission and pro‐apoptotic roles of Mtfp1 in DOX‐induced cardiotoxicity. DOX up‐regulates the Mtfp1 expression in HL‐1 cardiac myocytes. Knockdown of Mtfp1 prevents cardiac myocyte from undergoing mitochondrial fission, and subsequently reduces the DOX‐induced apoptosis by preventing dynamin 1‐like (Dnm1l) accumulation in mitochondria. In contrast, when Mtfp1 is overexpressed, a suboptimal dose of DOX can induce a significant percentage of cells to undergo mitochondrial fission and apoptosis. These data suggest that knocking down of Mtfp1 can minimize the cardiomyocytes loss in DOX‐induced cardiotoxicity. Thus, the regulation of Mtfp1 expression could be a novel therapeutic approach in chemotherapy‐induced cardiotoxicity. 相似文献
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Zavodovskaya M Campbell MJ Maddux BA Shiry L Allan G Hodges L Kushner P Kerner JA Youngren JF Goldfine ID 《Journal of cellular biochemistry》2008,103(2):624-635
We have reported that nordihydroguaiaretic acid (NDGA) inhibits the tyrosine kinase activities of the IGF-1 receptor (IGF-1R) and the HER2 receptor in breast cancer cells. Herein, we studied the effects of NDGA on the growth of estrogen receptor (ER) positive MCF-7 cells engineered to overexpress HER2 (MCF-7/HER2-18). These cells are an in vitro model of HER2-driven, ER positive, tamoxifen resistant breast cancer. NDGA was equally effective at inhibiting the growth of both parental MCF-7 and MCF-7/HER2-18 cells. Half maximal effects for both cell lines were in the 10-15 microM range. The growth inhibitory effects of NDGA were associated with an S phase arrest in the cell cycle and the induction of apoptosis. NDGA inhibited both IGF-1R and HER2 kinase activities in these breast cancer cells. In contrast, Gefitinib, an epidermal growth factor receptor inhibitor but not an IGF-1R inhibitor, was more effective in MCF-7/HER2-18 cells than in the parental MCF-7 cells and IGF binding protein-3 (IGFBP-3) was more effective against MCF-7 cells compared to MCF-7/HER2-18. MCF-7/HER2-18 cells are known to be resistant to the effects of the estrogen receptor inhibitor, tamoxifen. Interestingly, NDGA not only inhibited the growth of MCF-7/HER2-18 on its own, but it also demonstrated additive growth inhibitory effects when combined with tamoxifen. These studies suggest that NDGA may have therapeutic benefits in HER2-positive, tamoxifen resistant, breast cancers in humans. 相似文献
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地中海饮食,特别是橄榄油,赋予了地中海周边国家人民对于退行性疾病的强力抵抗,尤其是心血管疾病和肿瘤的发生率以及致死率相对更低。羟基酪醇是橄榄油中的多酚类化合物之一,在防治紫外辐射、糖尿病、老年性视网膜黄斑病变、心血管疾病以及肿瘤等方面都具有重要的生物学效应。将具体阐述羟基酪醇作为一种线粒体营养素（如通过调节线粒体的动态变化以及Nrf2介导的抗氧化酶的诱导等）如何促进其有益功能。 相似文献
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Jessica L. F. Teh Raj Shah Seung‐Shick Shin Yu Wen Janice M. Mehnert James Goydos Suzie Chen 《Pigment cell & melanoma research》2014,27(4):621-629
Our laboratory previously described the oncogenic properties of metabotropic glutamate receptor 1 (mGluR1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in mGluR1‐mediated melanocytic tumorigenesis in vivo. In particular, we identified AKT2 being the predominant isoform contributing to the activation of AKT. Suppression of Grm1 or AKT2 using an inducible Tet‐R siRNA system resulted in a 60 or 30% reduction, respectively, in in vivo tumorigenesis. We show that simultaneous downregulation of Grm1 plus AKT2 results in a reduction of approximately 80% in tumor volumes, suggesting that both mGluR1 and AKT2 contribute to the tumorigenic phenotype in vivo. The discrepancy between the mild in vitro transformation characteristics and the aggressive in vivo tumorigenic phenotypes of these stable mGluR1‐melanocytic clones led us to investigate the possible involvement of other growth factors. Here, we highlight a potential crosstalk network between mGluR1 and tyrosine kinase, insulin‐like growth factor 1 receptor (IGF‐1R). 相似文献
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《Journal of molecular biology》2022,434(9):167536
Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in regulating cellular metabolism and cell growth and has been identified as an anticancer drug target. Although previous studies have revealed some structures of IGF1R with different ligands, the continuous dynamic conformation change remains unclear. Here, we report 10 distinct structures (7.9–3.6 Å) of IGF1R bound to IGF1 or insulin to reveal the polymorphic conformations of ligand-bound IGF1R. These results showed that the α-CT2, disulfide bond (C670-C670′), and FnIII-2 domains had the most flexible orientations for the conformational change that occurs when ligands bind to the receptor. In addition, we found one special conformation (tentatively named the diverter-switch state) in both complexes, which may be one of the apo-IGF1R forms under ligand-treatment conditions. Hence, these results illustrated the mechanism of how different ligands could bind to human IGF1R and provided a rational template for drug design. 相似文献
15.
Hengli Ni Xiaoxiao Dai Xueqin Leng Min Deng Yan Qin Qinghua Ji Chunfang Xu Jianming Li Yao Liu 《Journal of cellular biochemistry》2018,119(8):6806-6813
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Yingbo Lin Hongyu Liu Ahmed Waraky Felix Haglund Prasoon Agarwal Helena Jernberg‐Wiklund Dudi Warsito Olle Larsson 《Journal of cellular physiology》2017,232(10):2722-2730
Increasing number of studies have shown nuclear localization of the insulin‐like growth factor 1 receptor (nIGF‐1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF‐1R have, however, still not been disclosed. Previously, we reported that IGF‐1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple‐SUMO‐site‐mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R‐). Cell clones (R‐WT and R‐TSM) expressing equal amounts of IGF‐1R were selected for experiments. Phosphorylation of IGF‐1R, Akt, and Erk upon IGF‐1 stimulation was equal in R‐WT and R‐TSM. WT was confirmed to enter nuclei. TSM did also undergo nuclear translocation, although to a lesser extent. This may be explained by that TSM heterodimerizes with insulin receptor, which is known to translocate to cell nuclei. R‐WT proliferated substantially faster than R‐TSM, which did not differ significantly from the empty vector control. Upon IGF‐1 stimulation G1‐S‐phase progression of R‐WT increased from 12 to 38%, compared to 13 to 20% of R‐TSM. The G1‐S progression of R‐WT correlated with increased expression of cyclin D1, A, and CDK2, as well as downregulation of p27. This suggests that SUMO‐IGF‐1R affects upstream mechanisms that control and coordinate expression of cell cycle regulators. Further studies to identify such SUMO‐IGF‐1R dependent mechanisms seem important. 相似文献
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Insulin-like growth factor II (IGF-II) plays a key role in mitogenesis during development and tumorigenesis and is believed to exert its mitogenic functions mainly through the IGF-I receptor. Recently, we identified the insulin receptor isoform A (IR(A)) as an additional high affinity receptor for IGF-II in both fetal and cancer cells. Here we investigated the mitogenic signaling of IGF-II via the Akt/Glycogen synthase kinase 3 (Gsk3) axis employing R-IR(A) cells that are IGF-I receptor null mouse embryonic fibroblasts expressing the human IR(A). IGF-II induced activation of the proto-oncogenic serine kinase Akt, reaching maximal at 5-10 min. IGF-II also caused the rapid and sustained deactivation of glycogen synthase kinase 3-beta (Gsk3beta), reaching maximal at 1-3 min, shortly preceding, therefore, maximal activation of Akt. Under our conditions, IGF-II and insulin induced 70-80% inhibition of Gsk3betaactivity. In these cells IGF-II also deactivated Gsk3alpha although less effectively than Gsk3beta. In parallel experiments, we found that IGF-II induced transient activation of extracellular-signal-regulated kinases (Erk) reaching maximal at 5-10 min and decreasing thereafter. Time courses and potencies of regulation of both mitogenic pathways (Akt/Gsk3beta and Erk) by IGF-II via IR(A) were similar to those of insulin. Furthermore, IGF-II like insulin effectively stimulated cell cycle progression from the G0/G1 to the S and G2/M phases. Interestingly, AP-1-mediated gene expression, that was reported to be negatively regulated by Gsk3beta was only weakly increased after IGF-II stimulation. Our present data suggest that the coordinated activation or deactivation of Akt, Gsk3beta, and Erk may account for IGF-II mitogenic effects and support an active role for IR(A) in IGF-II action. 相似文献
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Insulin‐like growth factor‐1 (IGF‐1) mediates some of growth hormone anabolic functions through its receptor, IGF‐1R. Following ligand binding, intracellular signaling pathways are activated favouring proliferation, cell survival, tissue growth, development, and differentiation. IGF‐1 is included in the World Anti‐Doping Agency Prohibited List. While the evidence for IGF‐1 as performance‐enhancing substrate in healthy humans is still weak, clinical studies demonstrated that the endogenous growth hormone/IGF‐1 excess is associated with cardiovascular implications. Previously, we demonstrated that human peripheral blood lymphocytes represent a suitable system to identify a gene signature, related to dihydrotestosterone or IGF‐1 abuse, independent from the type of sport. In addition, in a proteomic study, we demonstrated that dihydrotestosterone hyperdosage affects cell motility and apoptosis. Here, we investigate the doping action of IGF‐1 by means of a differential proteomic approach and specific protein arrays, revealing an active cytoskeletal reorganization mediated by Stat‐1; moreover, IGF‐1 stimulation produces a sustained activation of different signaling pathways as well as an overproduction of cytokines positively related to immune response and inflammation. In conclusion, these data indicate that, following IGF‐1 hyperdosage, circulating peripheral blood lymphocytes could be more prone to transendothelial migration. 相似文献
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以胰岛素样生长因子受体－1基因为靶筛选抗肿瘤药物.根据IGF1RmRNA的二级结构设计了9条反义寡核苷酸药物,以脂质体介导进行转染,MTT染色计算细胞生长抑制率,从中筛选出一条序列并对之进行优化,最后以最佳序列进行体外作用持续时间及体内细胞生长抑制率分析.结果表明该序列在体内外具有良好的抗肿瘤活性,具有剂量依赖性关系,且对荷瘤裸鼠无明显的毒性.IGF1R可作为肿瘤治疗的新靶点. 相似文献