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| 1 | Exosome-mediated transfer of miR-1290 promotes cell proliferation and invasion in gastric cancer via NKD1显示文摘Currently, exosomes rich in RNAs and proteins are regarded as vital mediators of intercellular communication. Here, we aimed to explore the effects of exosomal miR-1290 in gastric cancer (GC) and understand its mechanism of action on GC progression. We first isolated exosomes from serum samples of GC patients and healthy people and characterized them by transmission electron microscopy. Then, we examined the expression level of miR-1290 contained in the exosomes by quantitative reverse-transcription polymerase chain reaction and found that exosomal miR-1290 was overexpressed in GC patients and cell lines. Promotion of proliferation, migration, and invasiveness of GC cells was noted after they were incubated with the isolated miR-1290-rich exosomes compared with incubation with a negative control. Furthermore, we predicted that naked cuticle homolog 1 (NKD1) mRNA is a direct target of miR-1290 and confirmed their interaction by a dual luciferase reporter assay. NKD1 overexpression attenuated the stimulatory effects of miR-1290 on GC cells. Collectively, our results suggest that exosomal miR-1290 enhances GC cell proliferation and invasion by targeting NKD1 mRNA and downregulating NKD1 expression. A better understanding of this process may facilitate the development of novel therapeutic agents for GC. | Jiying Huang Manru Shen Meizhu Yan Ying Cui Zhenjun Gao Xin Meng | 2019 | Acta Biochimica et Biophysica Sinica2019，51，9： | 19 |
| 2 | Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease显示文摘The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients. | Sara Heebll Karen Louise Thomsen Steen B Pedersen Hendrik Vilstrup Jacob George Henning Grnbk | 2014 | World Journal of Hepatology2014，6，4： | 11 |
| 3 | EZH2和microRNA-101在急性髓系白血病中的相关性分析及对预后的影响显示文摘EZH2基因(enhancer of zeste homolog 2,EZH2)是果蝇ZESTE基因增强子的人类同源物,是PcG(Polycomb Group)家族中PRC2复合物的重要成员之一。 | 吴圣豪 郑翠苹 徐杰 | 2012 | 中华血液学杂志2012，33，3： | 10 |
| 4 | HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway显示文摘AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was observed.Endogenous ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by FACS-calibur.Identification of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing electrophoresis.RESULTS:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in vitro.Increased ROS were detected by HBx.Tumor suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased ROS.Increased oxidized PTEN activated the mitogenic pathway through over-activated Akt.However,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced form.Endogenously produced ROS also stimulated HBx expression.CONCLUSION:HBx induced ROS promoted Akt pathways via oxidized inactive PTEN.HBx and ROS maintained a positive regulatory loop,which aggravated carcinogenesis. | Hye-Lin Ha Dae-Yeul Yu | 2010 | World Journal of Gastroenterology2010，16，39： | 8 |
| 5 | 果蝇EZH2与乳腺癌分子分型及临床病理特征的关系显示文摘目的探讨果蝇Zeste基因增强子人类同源物2(EZH2)与乳腺癌分子分型及临床病理参数的关系。方法根据新型乳腺癌分子分型标准,将乳腺癌进行分子分型;免疫组织化学方法检测乳腺癌组织石蜡切片中EZH2的表达;采用χ~2检验分析EZH2表达与乳腺癌新型分子分型,以及临床病理参数之间的关系;采用KaplanMeier法分析EZH2表达与乳腺癌患者无病生存率(DFS)的关系。结果 13例管腔上皮A型乳腺癌患者中,3例为EZH2高表达(23.08%);10例管腔上皮B型乳腺癌患者中,5例为EZH2高表达(50.00%);7例人表皮生长因子受体2过表达型乳腺癌患者中,3例为EZH2高表达(42.86%);12例三阴性型乳腺癌患者中,10例为EZH2高表达(83.33%)。乳腺癌各分子亚型间EZH2表达的比较,差异有统计学意义(P<0.05)。EZH2高表达与EZH2低表达患者DFS比较,差异有统计学意义(P<0.05)。结论 EZH2可能是预测乳腺癌预后的指标之一。 | 李杰宝 喻晓程 田野 | 2017 | 中国现代医学杂志2017，27，6： | 8 |
| 6 | Long noncoding RNAs in hepatitis B virus-related hepatocellular carcinoma显示文摘AIM: To study the expression of long noncoding RNAs(lncRNAs) in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).METHODS: The lncRNA profiles between HBV-related HCC tissues and corresponding normal liver tissues were generated using microarray analysis. Datasets were analyzed using multiple algorithms to depict alterations in gene expression on the basis of gene ontology(GO), pathway analysis, and lncRNA levels.RESULTS: The microarray revealed that 1772 lncRNAs and 2508 mRNAs were differently expressed. The pathway analysis demonstrated that the cell cycle, cytokinecytokine receptor interaction, chemokine signaling pathway, and phosphoinositide 3-kinase-protein kinase B signaling pathway may play important roles in HCC.Several GO terms, such as cell cycle, DNA replication,immune response, and signal transduction, were enriched in gene lists, suggesting a potential correlation with HBVrelated HCC. The upregulated large intergenic noncoding RNA ULK4P2 was physically combined with enhancer of zeste homolog 2. Therefore, the lncRNAs may participate in regulating HBV-related HCC.CONCLUSION: lncRNAs play important roles in HCC,future studies should verify whether large intergenic noncoding ULK4P2 functions by combining with enhancer of zeste homolog 2 in HCC. | Ting-Ting Yu Xi-Ming Xu Yi Hu Jun-Jian Deng Wei Ge Na-Na Han Mei-Xia Zhang | 2015 | World Journal of Gastroenterology2015，21，23： | 7 |
| 7 | Anti-miRNA-221 sensitizes human colorectal carcinoma cells to radiation by upregulating PTEN显示文摘AIM:To investigate the regulative effect of miRNA(miR)-221 on colorectal carcinoma(CRC)cell radiosensitivity and the underlying mechanisms.METHODS:A human CRC-derived cell line was cultured conventionally and exposed to different doses of X-rays(0,2,4,6 and 8 Gy).The total RNA and protein of the cells were extracted 24 h after irradiation,and the alteration of miR-221 and phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene mRNA expression was detected by real-time reverse transcriptase polymerase chain reaction(PCR).The protein alteration of PTEN in the cells was detected by Western blotting.Caco2 cells were pretreated with or without anti-PTEN-siRNA prior to the addition of premiR-221 or anti-miR-221 using Lipofectamine 2000.Colony formation assay and flow cytometry analysis were used to measure the surviving cell fraction and the sensitizing enhancement ratio after irradiation.Ad-ditionally,PTEN 3′-untranslated region fragment was PCR amplified and inserted into a luciferase reporter plasmid.The luciferase reporter plasmid construct was then transfected into CRC cells together with premiR-221 or anti-miR-221,and the luciferase activity in the transfected cells was detected.RESULTS:The X-ray radiation dose had a significant effect on the expression of miR-221 and PTEN protein in human Caco2 cells in a dose-dependent manner.The miR-221 expression level improved gradually with the increase in irradiation dose,while the PTEN protein expression level reduced gradually.miR-221 expression was significantly reduced in the anti-miR-221 group compared with the pre-miR-221 and negative control groups(P<0.01).Anti-miR-221 upregulated expression of PTEN protein and enhanced the radiosensitivity of Caco2 cells(P<0.01).Moreover,the inhibitory effect was dramatically abolished by pretreatment with anti-PTEN-siRNA,suggesting that the enhancement of radiosensitivity was indeed mediated by PTEN.A significant increase of luciferase activity was detected in CRC cells that were cotransfected with the luciferase reporter plasmid construct and anti-miR-221(P<0.01).CONCLUSION:Anti-miR-221 can enhance the radiosensitivity of CRC cells by upregulating PTEN. | Qi Xue Kai Sun Hai-Jun Deng Shang-Tong Lei Jing-Qing Dong Guo-Xin Li | 2013 | World Journal of Gastroenterology2013，19，48： | 6 |
| 8 | Diffuse intestinal ganglioneuromatosis an uncommon manifestation of Cowden syndrome显示文摘Diffuse intestinal ganglioneuromatosis is a hamartomatous polyposis characterized by a disseminated, intramural or transmural proliferation of neural elements involving the enteric plexuses. It has been associated with MEN Ⅱ, neurofibromatosis type 1 and hamartomatous polyposis associated with phosphatase and tensin homolog mutation. We report the case of a female patient with a history of a breast and endometrial tumor who presented in a colonoscopy performed for rectal bleeding diffuse ganglioneuromatosis, which oriented the search for other characteristic findings of Cowden syndrome given the personal history of the patient. The presence of an esophagogastric polyposis was also noted. Cowden syndrome is characterized by skin lesions, but it is rarely diagnosed by these lesions, because they are usually overlooked. Intestinal polyposis is not a major diagnostic criterion but it is very useful for early diagnosis. The combination of colonic polyposis and glucogenic acanthosis should orient the diagnosis to Cowden syndrome. | Maria Teresa Herranz Bachiller Jesus Barrio Andrés Fernando Pons Noelia Alcaide Suárez Rafael Ruiz-Zorrilla Lorena Sancho del Val Sara Lorenzo Pelayo Carlos De La Serna Higuera Ramon Atienza Sánchez Manuel Perez Miranda | 2013 | World Journal of Gastrointestinal Oncology2013，5，2： | 5 |
| 9 | Alternative splicing of VEGFA,APP and NUMB genes in colorectal cancer显示文摘AIM:To investigate alternative splicing in vascular endothelial growth factor A(VEGFA),amyloid beta precursor protein(APP),and Numb homolog(NUMB) in colorectal cancer(CRC).METHODS:Real-time quantitative reverse transcriptase polymerase chain reaction(q RT-PCR) and PCRrestriction fragment length polymorphism analyses were performed to detect the expression of VEGFA,APP,and NUMB mR NA in 20 CRC tissues and matched adjacent normal tissues,as well as their alternative splicing variants.RESULTS:q RT-PCR analysis revealed that the expression of APP,NUMB,and VEGFA 165 b m RNA were significantly downregulated,while VEGFA m RNA was upregulated,in CRC tissues(all P < 0.05).PCRrestriction fragment length polymorphism analysis revealed that the expression of VEGFA 165a/b in CRC tissues was significantly higher than in adjacent normal tissues(P < 0.05).Compared with adjacent normal tissues,the expression of NUMB-PRRS in CRC tissues was significantly decreased(P < 0.05),and the expression of NUMB-PRRL was increased(P < 0.05).CONCLUSION:Alternative splicing of VEGFA,APP,and NUMB may regulate the development of CRC,and represent new targets for its diagnosis,prognosis,and treatment. | Yi-Jun Zhao Hua-Zhong Han Yong Liang Chen-Zhang Shi Qing-Chao Zhu Jun Yang | 2015 | World Journal of Gastroenterology2015，21，21： | 4 |
| 10 | Clinical correlation of B7-H3 and B3GALT4 with the prognosis of colorectal cancer显示文摘AIM To investigate the expression and clinical significance of B7 homolog 3(B7-H3) and β-1,3-galactosyltransferase-4(B3 GALT4) in colorectal cancer(CRC) patients.METHODS Using tissue microarray, we identified the expression of B7-H3 and B3 GALT4 in 223 CRC patient samples by immunohistochemistry and evaluated the possible correlation between B7-H3 and B3 GALT4 and clinicaloutcomes. Further, the m RNA and protein expression were identified to establish the regulatory relationship of B7-H3 with B3 GALT4 in vitro.RESULTS A significant positive correlation between B7-H3 and B3 GALT4 was observed in CRC specimens(r = 0.219, P = 0.001). High expression of B7-H3 was identified as a significant independent predictor of poor overall survival(OS) [hazard ratio(HR) = 1.781; 95%CI: 1.027-3.089; P = 0.040]. Moreover, high expression of B3 GALT4 was also recognized as an independent predictor of inferior OS(HR = 1.597; 95%CI: 1.007-2.533; P = 0.047). Additionally, CRC patients expressing both high B7-H3 and high B3 GALT4 contributed to a significant decrease in OS(HR = 2.283; 95%CI: 1.289-4.042; P = 0.005). In CRC cell lines with stable expression of high B7-H3, the m RNA and protein expressions of B3 GALT4 were significantly upregulated. Similarly, the expression of B3 GALT4 was significantly reduced when expression of B7-H3 was knocked down.CONCLUSION The expression of B3 GALT4 in CRC is positively correlated with B7-H3 expression in vitro. B7-H3/B3 GLAT4 may be used as dual prognostic biomarkers for CRC. | Ting Zhang Fang Wang Jing-Yi Wu Zhi-Chao Qiu Yan Wang Fen Liu Xiao-Song Ge Xiao-Wei Qi Yong Mao Dong Hua | 2018 | World Journal of Gastroenterology2018，24，31： | 4 |
| 11 | B7家族新成员显示文摘 | 曹旭东 孔令洪 王一理 | 2003 | 细胞与分子免疫学杂志2003，19，4： | 4 |
| 12 | Hugl-1 induces apoptosis in esophageal carcinoma cells both in vitro and in vivo显示文摘AIM: To determine whether the human giant larvae homolog 1 gene (Hugl-1/Llg1/Lgl1) exerts tumor suppressor effects in esophageal cancer. METHODS: We constructed a Hugl-1 expression plasmid, pEZ-M29-Hugl1, for gene transfection. We transfected the pEZ-M29-Hugl1 plasmid into Eca109 esophageal cancer cell lines with Lipofectamine 2000 to overexpress Hugl-1. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the effects of the plasmid on Hugl-1 expression. In vitro cell proliferation and apoptosis were examined separately by cell counting Kit-8 (CCK-8) assay, flow cytometry, and Western blotting before and after the transfection of the plasmid into Eca109 cells. Cell cycle distribution was assessed with flow cytometry. The effect of Hugl-1 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice. Expression of Hugl-1 in xenograft tumor was analyzed by immunohistochemistry.The transferase-mediated dUTP nick end-labeling (TUNEL) technique was performed to detect and quantitate apoptotic cell. RESULTS: The transfection efficiency was confirmed with real-time RT-PCR and Western blotting. Our results show that compared with control groups the mRNA levels and protein levels of Hugl-1 in pEZ-M29-Hugl1-treated group were remarkably increased (P < 0.05). The CCK-8 assay demonstrated that the growth of cells overexpressing Hugl-1 was significantly lower than control cells. Cell cycle distribution showed there was a G 0 /G 1 cell cycle arrest in cells overexpressing Hugl-1 (64.09% ± 3.14% vs 50.32% ± 4.60%, 64.09% ± 3.14% vs 49.13% ± 2.24%). Annexin V-fluorescein isothiocyanate revealed that apoptosis was significantly increased in cells overexpressing Hugl-1 compared with control group (17.33% ± 4.76% vs 6.90% ± 1.61%, 17.33% ± 4.76% vs 6.27% ± 0.38%). Moreover, we found that Hugl-1 changes the level of the anti-apoptotic protein Bcl-2 and the proapoptotic protein Bax and the activation of both caspase-3 and caspase-9. With a TUNEL assay, we found that Hugl-1 markedly increased the apoptosis rate of Eca109 cells in vivo (60.50% ± 9.11% vs 25.00% ± 12.25%). It was shown that Hugl-1 represents a significantly more effective tumor suppressor gene alone in a xenograft tumor mouse model. This data suggest that Hugl-1 inhibited tumor growth and induced cell apoptosis in vivo . CONCLUSION: These results suggest that Hugl-1 induces growth suppression and apoptosis in a human esophageal squamous cell carcinoma cell line both in vitro and in vivo . | Jia Song Xiu-Lan Peng Meng-Yao Ji Ming-Hua Ai Ji-Xiang Zhang Wei-Guo Dong | 2013 | World Journal of Gastroenterology2013，19，26： | 4 |
| 13 | PLZF^posc-KIT^pos-delineated A1-A4-differentiating spermatogonia by subset and stage detection upon Bouin fixation显示文摘While hallmarks of rodent spermatogonia stem cell biomarkers' heterogeneity have recently been identified, their stage and subset distributions remain unclear. Furthermore, it is currently difficult to accurately identify subset-specific SSC marker distributions due to the poor nuclear morphological characteristics associated with fixation in 4% paraformaldehyde. In the present study, testicular cross-sections and whole-mount samples were Bouin fixed to optimize nuclear resolution and visualized by immunohistochemistry (IHC) and immunofluorescence (IF). The results identified an expression pattern of PLZFhighc-KITpos in A1 spermatogonia, while A2–A4-differentiating spermatogonia were PLZFlowc-KITpos. Additionally, this procedure was used to examine asymmetrically expressing GFRA1 and PLZF clones, asymmetric Apr and false clones were distinguished based on the presence or absence of TEX14, a molecular maker of intercellular bridges, despite having identical nuclear morphology and intercellular distances that were <25 μm. In conclusion, this optimized Bouin fixation procedure facilitates the accurate identification of spermatogonium subsets based on their molecular profiles and is capable of distinguishing asymmetric and false clones. Therefore, the findings presented herein will facilitate further morphological and functional analysis studies and provide further insight into spermatogonium subtypes. | Rui-Ling Tang Li-Qing Fan | 2019 | Asian Journal of Andrology2019，21，3： | 3 |
| 14 | 中国人非小细胞肺癌B-RAF基因(V600E)突变的研究显示文摘鼠类肉瘤滤过性毒菌致癌性同源体B1(v-raf murine sarcoma viral oncogene homolog B1,B-RAF)基因编码的蛋白为M a PK通路中的丝氨酸苏氮酸蛋白激酶,该酶将信号从RAS转导至EKI/2,从而参与调控多种生物学事件,如细胞生长、分化和凋亡等。BRAF在多种肿瘤存在突变,其中以结直肠癌突变率最高,突变率约为15%左右, | 翟笃明 王松林 贾淞淋 郭成业 | 2012 | 中国实验诊断学2012，16，2： | 3 |
| 15 | A soluble FcγR homolog inhibits Ig M antibody production in ayu spleen cells显示文摘Classical Fc receptors (FcRs) mediate the binding to and recognition of the Fc portion of antibodies and play an important role during immune responses in mammals. Although proteins similar to soluble FcRs have been identified in fish, little is known about the role of such proteins in fish immunity. Here, we cloned a cDNA sequence encoding a soluble Fc receptor for an immunoglobulin G (FcγR) homolog from ayu (Plecoglossus altivelis)(PaFcγRl). The predicted protein was composed of two immunoglobulin C2-like domains but lacked a transmembrane segment and a cytoplasmic tail. The PaFcγRl transcripts were distributed at low levels in all tested tissues, but significantly increased after Vibrio anguillarum infection. The PaFcγRl protein was expressed in the head kidney, trunk kidney, and neutrophils. Recombinant PaFcγRl (rPaFcγRl) was secreted when transfected into mammalian cells and the native protein was also detected in serum upon infection. rPaFcγRl was also demonstrated to bind to ayu IgM, as assessed by cell transfection. Suppressive activity of the recombinant mature protein of PaFcγRl (rPaFcγRlm) on in vitro anti-sheep red blood cell (SRBC) responses was detected by a modified hemolytic plaque forming cell assay. In conclusion, our study revealed that PaFcγRl is closely involved in the negative regulation of IgM production in the ayu spleen. | Kai Chen Yu-Hong Shi Jiong Chen Ming-Yun Li | 2019 | Zoological Research2019，40，5： | 3 |
| 16 | Mechanisms mediating the effects of alcohol and HIV anti-retroviral agents on mTORC1,mTORC2 and protein synthesis in myocytes显示文摘Alcoholism and acquired immune deficiency syndrome are associated with severe muscle wasting.This impairment in nitrogen balance arises from increased protein degradation and a decreased rate of protein synthesis.The regulation of protein synthesis is a complex process involving alterations in the phosphorylation state and protein-protein interaction of various components of the translation machinery and mammalian target of rapamycin(mTOR) complexes.This review describes mechanisms that regulate protein synthesis in cultured C2C12 myocytes following exposure to either alcohol or human immunodeficiency virus antiretroviral drugs.Particular attention is given to the upstream regulators of mTOR complexes and the downstream targets which play an important role in translation.Gaining a better understanding of these molecular mechanisms could have important implications for preventing changes in lean body mass in patients with catabolic conditions or illnesses. | Ly Q Hong-Brown Abid A Kazi Charles H Lang | 2012 | World Journal of Biological Chemistry2012，3，6： | 2 |
| 17 | EYA4通过抑制NF-κB依赖的RAP1反式激活抑制肝细胞癌的生长和侵袭显示文摘背景与目的我们之前研究表明,眼缺失蛋白同源物4(eyes absent homolog 4,EYA4)是果蝇眼部发育相关的眼缺乏蛋白家族成员之一,在肝细胞癌(hepatocellular carcinoma,HCC)标本中常发生甲基化和沉默,并与患者生存期短密切相关。本研究旨在探讨EYA4在HCC中作为肿瘤抑制因子的作用机制。方法转染EYA4表达质粒(pEYA4)构建稳定表达EYA4的人HCC细胞系Huh-7和PLC/PRF/5(PLC)。通过BALB/c裸鼠皮下注射稳定转染细胞建立异种移植肿瘤。组织标本来自75例病理诊断为HCC的患者。采用实时定量聚合酶链式反应(real-time polymerase chain reaction,real-time PCR)、蛋白质免疫印迹和免疫组织化学的方法检测EYA4在细胞系、异种移植物和临床标本中的表达;研究了稳定转染细胞系的细胞增殖、克隆形成、侵袭性和肿瘤形成。利用基因表达芯片筛选EYA4调节的基因。通过共转染EYA4和带Flag标签的RAS相关蛋白1A(RAS-related protein 1A,RAP1A)基因的表达质粒(pEYA4和Flag-RAP1A)、功能研究、染色质免疫共沉淀、免疫荧光染色和细胞泛素化分析等方法,研究了EYA4对核因子-κB(nuclear factor-κB,NF-κB)/RAS相关蛋白1(RAS-related protein 1,RAP1)信号通路的影响。结果恢复HCC细胞系中EYA4的表达可抑制细胞的增殖、抑制克隆形成、降低细胞的侵袭性和抑制异种移植肿瘤生长,在体外实验中Flag-RAP1A可逆转pEYA4的抑制作用。用肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)激活NF-κB通路可增加p65与RAP1A基因启动子的结合并上调RAP1蛋白的表达。用BAY 11-7085和p65 siRNA抑制NF-κB通路,成功阻断了TNF-α诱导的RAP1上调。EYA4拮抗了TNF-α诱导的NF-κB抑制因子α(inhibitor of NF-κBα,IκBα)的磷酸化和泛素化以及p65的核易位和反式激活,进而抑制了NF-κB的活性和RAP1的表达。用calyculin A阻断EYA4的丝氨酸/苏氨酸磷酸酶活性可显著消除其对NF-κB活性的抑制作用。此外,EYA4的表达与HCC临床标本中IκBα/RAP1活性呈负相关。结论我们的研究结果为明确EYA4是真正的肿瘤抑制因子提供了功能和机制的理论基础,该肿瘤抑制因子可抑制NF-κB/RAP1信号通路的异常激活,从而抑制HCC生长和侵袭。 | Shi-Jing Mo Xun Hou Xiao-Yi Hao Jian-Peng Cai Xin Liu Wei Chen Dong Chen Xiao-Yu Yin胆胰外科 | 2019 | 癌症2019，38，2： | 2 |
| 18 | phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease显示文摘AIM: To investigate the protein expression of phosphatase and tensin homolog(PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffinembedded liver sections of patients with non-alcoholic fatty liver disease(NAFLD)(n = 44) or alcoholic liver disease(ALD)(n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients' clinical history.RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis(r = 0.3061, P = 0.0459) and the BMI(r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor(P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients(P < 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD. | Andrea Sanchez-Pareja Sophie Clément Marion Peyrou Laurent Spahr Francesco Negro Laura Rubbia-Brandt Michelangelo Foti | 2016 | World Journal of Gastroenterology2016，22，14： | 2 |
| 19 | 第10号染色体缺失的磷酸酶张力蛋白同源物基因在IGFBPrP1诱导的大鼠肝纤维化中的作用显示文摘第10号染色体缺失的磷酸酶张力蛋白同源物基因(phosphatase and tensin homolog deleted onc hromosome ten,PTEN)是目前发现的第1个具有蛋白磷酸酶活性和脂质磷酸酶活性的抑癌基因,其中脂质磷酸酶活性是其最主要特征[1]。 | 樊晓 张海燕 刘立新 郭晓红 | 2014 | 中国药物与临床2014，14，8： | 2 |
| 20 | PTEN参与神经干细胞调控及脊髓损伤修复的研究进展显示文摘1997年,第10号染色体缺失的磷酸酶与张力蛋白同源物基因(phosphatase and tensin homolog deleted on chromosome 10,PTEN)由国外3个独立的研究小组先后克隆命名,这是目前发现的第一个具有磷酸酶活性的抑癌基因,其编码的蛋白在细胞内具有脂质磷酸酶和蛋白磷酸酶的双重活性。PTEN具有广泛的生物学功能,通过细胞内多个信号通路来调控细胞的生长、分化、迁移、凋亡等过程。 | 宋志文 余常麟 丁亚 邹红军 刘锦波 | 2016 | 中国脊柱脊髓杂志2016，26，6： | 2 |
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