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IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

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Genes & Diseases 2024年第1期11卷 495-508页

作者： Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang qingli bie Rou Zhao Li Wei Baogui Zhang Bin Zhang Department of Laboratory Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine JinanShandong 250355China Department of Reproductive Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal Surgery Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Institute of Forensic Medicine and Laboratory Medicine Jining Medical UniversityJiningShandong 272067China

Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease *** these rare cancer cells,however,remains challenging with respect to therapeutic ***,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid *** expression of IL-13RA2 was positively correlated with canonical stemness markers in *** further demonstrated that the level of IL-13 was up-regulated in the serum of CRC ***,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in *** phenotype could be reversed by knocking down ***,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of *** further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of *** conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.

关键词： Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53

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IL-17B/IL-17RB signaling regulates lysine 63-linked Beclin-1 ubiquitination to strengthen self-renewal and tumorigenesis in gastric cancer

IL-17B/IL-17RB signaling regulates lysine 63-linked Beclin-1...

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中国生物化学与分子生物学会2019年全国学术会议暨学会...

作者： qingli bie Haixin Dong Bin Zhang Department of Laboratory Medicine Affiliated Hospital of Jining Medical University Institute of Forensic Medicine and Laboratory Medicine Jining Medical University

Cancer stem cells(CSCs) display many malignant biological traits including tumorigenesis, metastasis, drug resistance and angiogenesis. Discovering new markers specific for CSCs and elucidating their regulatory mechanisms is a significant goal. Herein, we found that IL-17 B/IL-17 RB signaling promoted self-renewal and tumorigenesis of gastric cancer(GC) cells by activating autophagy. We identified this pathway by first determining that IL-17 RB expression is significantly upregulated in spheroid cells, which was closely associated with the degree of differentiation of patient-derived GC tissues. Exogenous recombinant IL-17 B(rIL-17 B) promoted the self-renewal capacity of GC cells in vitro and enhanced tumor growth and metastasis in vivo. Moreover, we found that rIL-17 B induced autophagosome formation and cleavage-mediated transformation of LC3 in GC and 293 T cells. Interestingly, inhibition of autophagy by ATG7 knockdown reversed rIL-17 B induced self-renewal of GC cells. Further study revealed that rIL-17 B promoted K63-linked ubiquitination of beclin-1 by mediating the binding of TRAF6 to beclin-1. Interfering with IL-17 RB expression abolished all the effects of rIL-17 B on ubiquitination of beclin-1 and autophagic activation of GC cells. Lastly, we discovered that IL-17 B expression in the serum of patients was positively correlated with IL-17 RB expression in GC tissues. In addition, rIL-17 B increased IL-17 RB expression in GC cells. Direct overexpression of IL-17 RB in 293 T cells mimics stimulated rIL-17 B, which promoted K63-linked ubiquitination of beclin-1 and binding of TRAF6 to beclin-1. Together, these results revealed the novel action of IL-17 B/IL-17 RB signaling on CSCs and might provide new therapeutic targets against gastric cancer.

关键词： IL-17B IL-17RB autophagy K63-linked ubiquitination of Beclin-1 gastric cancer cancer stem cell

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Paracrine mechanism of interleukin-17B receptor potentiates tumor growth and migration via AKT/β-catenin pathway in gastric cancer

Paracrine mechanism of interleukin-17B receptor potentiates ...

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第十届全国免疫学学术大会

作者： qingli bie Zhaoliang Su Shengjun Wang Huaxi Xu Jiangsu University

Inflammation is a critical component involved in tumor progression. IL-17 cytokine family, though still young since discovery, has recently emerged as important players in diseases. However, the role of IL-17B/IL-17RB(interleukin-17 receptor B) signal in tumor growth and migration remains unknown. In this study, we firstly confirmed that the expression levels of IL-17 B and IL-17 RB was significantly increased in gastric cancer tissues, and there were positive correlations between IL-17 RB and some stemness markers. Furtherly, we used the IL-17RB-sh RNA to interfere the expression of IL-17 RB in MGC-803 cell lines which expressed higher IL-17 RB, and found the ability of cell proliferation and migration or expression of E-cadherin, N-cadherin, Nanog, Sox 2 and Oct 4 protein were obviously influenced in the presence of exogenous r IL-17 B compared with GFP-sh RNA transfected MGC-803. Simultaneously, the expression of phosphorylated ERK1/2 and STAT3 have no obvious change, whereas the expression of phosphorylated AKT, GSK-3β and β-catenin as well as the nuclear translocation of β-catenin were significantly increased in MGC-803 cell lines expressed higher IL-17 RB in a dose-dependent manner. The AKT inhibitor, LY294002 could reverse IL-17B-induced upregulation of β-catenin and some stemness markers. Our data indicate that the IL-17B/IL-17 RB axis can promote the growth and migration of tumor cells through up-regulating the cells stemness and activating AKT/β-catenin pathway in gastric cancer, and suggest that IL-17 RB as a novel target may contribute to human gastric cancer therapy.

关键词： IL-17B/IL-17BR axis AKT/β-catenin pathway Stemness MGC-803 Gastric cancer

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Together,Elevated Alternatively Activated Macrophages,Myeloid-Derived Suppressor Cells and Th2 Cells Polarization Foster an Immunosuppressive Environment in Esophageal Cancer Patients

Together,Elevated Alternatively Activated Macrophages,Myeloi...

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中华医学会2014全国微生物学与免疫学学术年会

作者：高晶晶许化溪 Shengjun Wang Yumin Wu Zhaoliang Su Prince Amoah Bamie Zhijun Jiao qingli bie Liwei Lu 江苏大学医学院免疫研究室 Department of Laboratory Medicine Suzhou Hospital Affiliated to Nanjing Medical University Department of Laboratory Medicine Affiliated Hospital of Jiangsu University

Background During carcinogenesis,myeloid derived suppressor cells(MDSCs)and M2macrophages,as major host components contributing to the suppressive environment of tumor *** we showed that there was a predominant Th2 ph...

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<i>Cedecea lapagei</i>in a Patient with Multiple Injuries: Report of a Rare Case

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Journal of Biosciences and Medicines 2021年第11期9卷 1-5页

作者： Xiaofan Xu Kaiyue Chang Dongxue Song Guangtong Tian Xiaohang Hu Liqing Jiang Bin Zhang qingli bie Shuhua Lu Xiaozhe Li Haixin Dong Chengqiang Jin School of Clinical Medicine Jining Medical University Jining China Department of Clinical Laboratory Jining Hospital of traditional Chinese Medicine Jining China Department of Clinical Laboratory The Affiliated Hospital of Jining Medical University Jining China

Cedecea lapagei (C. lapagei) is an opportunistic pathogen in old patients with many comorbid diseases and the immunosuppressed. It is a gram-negative, facultative anaerobe bacterium of the Enterobacteriaceae family. We present a rare case of a patient with multiple injuries, C. lapagei was found from the exudate of the wound, what’s more, the Proteus vulgaris was also found in blood culture medium at the same time. According to the available literature, this is the first case of simultaneous infection of two bacteria including C. lapagei and Proteus vulgaris from the exudate of the traumatic wound.

关键词： C. lapagei Cedecea Proteus vulgaris Exudate

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不同砂率下再生透水混凝土基本性能分析

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人民黄河 2020年第8期42卷 131-135页

作者：王庆利陈守开蒋海峰陈家林别亚静郭磊河南水利投资集团有限公司河南郑州450002 华北水利水电大学水利学院河南郑州450045 河南省水环境模拟与治理重点实验室河南郑州450045 水资源高效利用与保障工程河南省协同创新中心河南郑州450045

通过再生骨料透水混凝土在不同砂率掺量条件下的试验,研究其强度与渗透性能的变化趋势与表现特征。在此基础上,将试块经切割机进行切面处理并基于Image方法提取其截面孔隙,观察其内部孔隙结构分布在不同砂率掺量下的变化情况,将其量化... 详细信息

通过再生骨料透水混凝土在不同砂率掺量条件下的试验,研究其强度与渗透性能的变化趋势与表现特征。在此基础上,将试块经切割机进行切面处理并基于Image方法提取其截面孔隙,观察其内部孔隙结构分布在不同砂率掺量下的变化情况,将其量化后与宏观的强度与渗透性能的测试结果相融合。结果显示:随着砂率的增大,再生骨料透水混凝土的强度与渗透性能分别表现为升高和降低,而量化的孔隙结构也出现了相应增减趋势;Image方法能够用于再生骨料透水混凝土的孔隙结构的提取,且孔隙面积与孔隙个数是影响再生骨料透水混凝土强度与渗透性能的主要因素。

关键词：再生骨料透水混凝土砂率掺量 Image法孔隙结构

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