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Identification of miR-515-3p and its targets,vimentin and MMP3,as a key regulatory mechanism in esophageal cancer metastasis:functional and clinical significance

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Signal Transduction and Targeted Therapy 2020年第1期5卷 206-218页

作者： Hui-Fang Hu Wen Wen Xu Wei-Xia Zhang Xin Yan Yang-Jia Li Bin Li Qing-Yu He Key Laboratory of Functional Protein research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology Institute of Life and Health EngineeringJinan UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Bioengineering Medicine and MOE Key Laboratory of Tumor Molecular Biology National Engineering Research Center of Genetic MedicineInstitute of BiomedicineCollege of Life Science and TechnologyJinan UniversityGuangzhouChina

Metastasis is the main factor of treatment failure in cancer patients,but the underlying mechanism remains to be elucidated and effective new treatment strategies are urgently *** study aims to explore novel key metastasis-related microRNAs(miRNAs)in esophageal squamous cell carcinoma(ESCC).By comparing miRNA profiles of the highly metastatic ESCC cell sublines,we established through serial in vivo selection with the parental cells,we found that the expression level of miR-515-3p was lower in ESCC tumor tissues than adjacent normal tissues,further decreased in metastatic tumors,and moreover,markedly associated with advanced stage,metastasis and patient *** in vitro and in vivo assays suggested that miR-515-3p could increase the expression of the epithelial markers as well as decrease the expression of the mesenchymal markers,and more importantly,suppress invasion and metastasis of ESCC ***,we revealed that miR-515-3p directly regulated vimentin and matrix metalloproteinase-3(MMP3)expression by binding to the coding sequence and 3′untranslated region,*** addition,the data from whole-genome methylation sequencing and methylation-specific PCR indicated that the CpG island within miR-515-3p promoter was markedly hypermethylated in ESCC cell lines and ESCC tumor tissues,which may lead to deregulation of miR-515-3p expression in ***,our preclinical experiment provides solid evidence that systemic delivery of miR-515-3p oligonucleotide obviously suppressed the metastasis of ESCC cells in nude *** together,this study demonstrates that miR-515-3p suppresses tumor metastasis and thus represents a promising prognostic biomarker and therapeutic strategy in ESCC.

关键词： metastasis esophageal markedly

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Construction of Magnetic Resonance Imaging Visible Polymeric Vector for Efficient Tumor Targeted siRNA Delivery

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Chinese Journal of Polymer Science 2022年第9期40卷 1071-1079页

作者： Rong-Ze Wang Si Huang Qiao-Yun Zhang Xing-Su Yu Ke-Ze Hong Jian-Rong Cao Hong Xiao Yong Wang Xin-Tao Shuai College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China Nanomedicine research center The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of Reproductive Medical center Guangdong Women and Children HospitalGuangzhou 511400China

RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer ***,an effective approach for siRNA delivery is urgently needed to meet the needs for its clinical ***,we constructed a polymeric vector labeled with superparamagnetic iron oxide(SPIO)for magnetic resonance imaging(MRI)visible siRNA *** antibody was also modified to the surface of nanodrug to enhance the delivery *** results showed that the vector exhibited great siRNA complexation ability and mediated an increased endocytosis of siRNA without obvious ***,both in vitro and in vivo studies evidenced the vector could effectively deliver siRNA into tumor cells,exert highly interfering effect,and show potent MR imaging *** study provides a promising MRI-visible and EGFR targeting delivery system to improve RNAi efficacy for cancer therapy.

关键词： Polymeric vector siRNA delivery Magnetic resonance imaging visible Tumor targeting

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Advances in targeted therapy for esophageal cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 585-595页

作者： Yan-Ming Yang Pan Hong Wen Wen Xu Qing-Yu He Bin Li MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein research of Guangdong Higher Education Institutes Institute of Life and Health EngineeringJinan UniversityGuangzhouChina MOE Key Laboratory of Tumor Molecular Biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic MedicineInstitute of BiomedicineCollege of Life Science and TechnologyJinan UniversityGuangzhouChina

Esophageal cancer(EC)is one of the most lethal cancers in the world,and its morbidity and mortality rates rank among the top ten in ***,surgical resection,radiotherapy and chemotherapy are the primary clinical treatments for esophageal ***,outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional *** a new type of approach,targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer;these include cetuximab and bevacizumab,which target epidermal growth factor receptor(EGFR)and vascular endothelial growth factor(VEGF),*** addition,other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously *** example,trastuzumab,a monoclonal antibody targeting human epidermal growth factor receptor 2(HER-2),has been approved by the Food and Drug Administration(FDA)as a first-line treatment of HER-2-positive ***,the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma(ESCC).These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer ***,adverse events,optimal dosages and effective combinations still need further *** this review,we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs,discuss their efficacy and safety,and provide a clinical rationale for precision medicine in esophageal cancer.

关键词： esophageal drugs targeted

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Cuproptosis: copper-induced regulated cell death

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Science China(Life Sciences) 2022年第8期65卷 1680-1682页

作者： Wen-Jun Duan Rong-Rong He Guangdong Engineering research center of Chinese Medicine&Disease Susceptibility Jinan UniversityGuangzhou 510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug development of Chinese Ministry of Education(MOE) Jinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs research Jinan UniversityGuangzhou 510632China School of Traditional Chinese Medicine Jinan UniversityGuangzhou 510632China

“Life is pleasant. Death is peaceful. It's the transition that's troublesome.”——Isaac Asimov Copper is an essential trace element central to cardiovascular, neuronal, and immune functions. While copper deficiency ... 详细信息

关键词： functions copper peace

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Light-activated nitric-oxide overproduction theranostic nanoplatform based on long-circulating biomimetic nanoerythrocyte for enhanced cancer gas therapy

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Science China Chemistry 2021年第10期64卷 1796-1810页

作者： Cheng-Guang Wu Jing-Lan Liang Xiang Wang Xiaoyan Zhou Xiang Cai Jun Xu Meng Wang Wen-Bo Wang Dong Ma Wei Xue Guangdong Provincial Engineering and Technological research center for Drug Carrier development Department of Biomedical EngineeringJinan UniversityGuangzhou 510632China Institute of Medicine and Health Guangdong Academy of SciencesNational Engineering Research Center for Healthcare DevicesGuangdong Key Lab of Medical Electronic Instruments and Polymer Material ProductsGuangdong Institute of Medical InstrumentsGuangzhou 510500China Department of Lighl Chemical Engineering Guangdong PolytechnicFoshan 528041China Department of Critical Care Medicine First Affiliated HospitalJinan UniversityGuangzhou 510632China MOE Key Laboratory of Tumor Molecular Biology Jinan UniversityGuangzhou 510632China

The limited intratumoral perfusion of nitric oxide(NO)-carrying nanoparticles into solid tumors caused by the inherent biological barriers in vivo greatly attenuates their generated efficacy. Herein, through entrapping heat-sensitive NO donors(BNN6)on mesoporous polydopamine nanoparticles(M-PDA) and subsequently enveloping with red blood cells membranes, a heatresponsive biomimetic theranostic nanoerythrocyte(M/B@R) is developed to boost NO-based cancer therapy. The reserved intact structure of red blood cells membranes(RBCm) endows M/B@R with superior biosafety and stealth properties for prolonged circulation time and subsequent enhanced tumor accumulation. Once internalized in tumors and excited by nearinfrared light(NIR, 808 nm) irradiation, M/B@R can not only yield plenty of heat for photothermal therapy(PTT) but also achieve the overproduction of NO for highly-efficient NO gas therapy due to its high loading capacity and NIR-absorbing property of M-PDA. The generated NO further ensures the formation of ONOO^(-) which possesses remarkable toxicity to tumor as well as alleviating tumor hypoxia. It is found that M/B@R with NIR as the excitation source can significantly induce synthetic lethality to tumors via the hyperthermia, DNA damage and the ease of tumor hypoxia. Simultaneously, M/B@R also exhibits the potential for bimodal fluorescence and photothermal imaging. The RBCm-camouflaged NO delivery nanoplatform with bimodal imaging capability in this work may provide a new combinatorial paradigm to induce PTT/NO for cancer theranostic applications.

关键词： nitric oxide biomimetic nanoerythrocyte PTT/NO synergistic therapy bimodal imaging

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Evolution of Influenza A H7N9 Virus with an Emphasis on Gene Constellation

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Journal of Genetics and Genomics 2014年第1期41卷 3-6页

作者： Zifeng Yang Runfeng Li Tianyu Zhang State Key Laboratory of Respiratory Disease The First Affiliated HospitalGuangzhou Medical University guangzhou Institute of Respiratory Disease National Clinical research center for Respiratory Disease center for Infection and Immunity Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences

The H7 subtype avian influenza viruses, including H7N2, HTN3 and HTN7, have posed a public health threat worldwide. Except one H7N7 fatal case in the Netherlands in 2003, the other H7 human cases have resulted in self... 详细信息

关键词： In gene Evolution of Influenza A H7N9 Virus with an Emphasis on Gene Constellation

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Insm1 regulates mTEC development and immune tolerance

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Cellular & Molecular Immunology 2023年第12期20卷 1472-1486页

作者： Weihua Tao Zhihuan Ye Yiqiu Wei Jianxue Wang Weixin Yang Guoxing Yu Jieyi Xiong Shiqi Jia The First Affiliated Hospital of jinan University GuangzhouChina The Guangdong-Hong Kong-Macao Joint University Laboratory of Metabolic and Molecular Medicine Jinan UniversityGuangzhouChina The Institute of Clinical Medicine Jinan UniversityGuangzhouChina Key Lab of guangzhou Basic and Translational research of Pan-Vascular Diseases GuangzhouChina Max Delbrück center for Molecular Medicine in the Helmholtz Association BerlinGermany VIB-KU Leuven center for Cancer Biology LeuvenBelgium

The expression of self-antigens in medullary thymic epithelial cells(mTECs)is essential for the establishment of immune tolerance,but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly ***,we show that Insm1,a zinc finger protein with known functions in neuroendocrine and neuronal cells,is broadly coexpressed with an autoimmune regulator(Aire)in ***1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic *** of Insm1 in mice downregulated Aire expression,dysregulated the gene expression program of mTECs,and altered mTEC subpopulations and the expression of tissue-restricted *** with these findings,loss of Insm1 resulted in autoimmune responses in multiple peripheral *** found that Insm1 regulates gene expression in mTECs by binding to ***,the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer ***,our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.

关键词： Medullary thymic epithelial cells(mTECs) Mimetic cells Tissue-restricted antigens(TRAs) Insulinoma-associated protein 1(lnsm1) Autoimmunity Autoimmune regulator(Aire)

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Pro-apoptotic effect of cecropin AD on nasopharyngeal carcinoma cells

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Chinese Medical Journal 2006年第12期119卷 1042-1046页

作者： XIAO Ye-chen HUANG Ya-dong XU Pei-lin ZHOU Zhen-qing LI Xiao-kun Biotechnology research center Key Laboratory of GeneEngineering Ministry of Education Sun Yat-sen UniversityGuangzhou 510275 China Biopharmaceutical research ＆ development center Jinan University Guangzhou 510632 China Department of Zoology Miami UniversityOxford 45056 USA School of Pharmaceutical Sciences Wenzhou Medical CollegeWenzhou 325035 China

Nasopharyngeal carcinoma （NPC） is one of the highly prevalent malignancies in Southeast Asia. Chemotherapy and radiotherapy are commonly administrated to treat nasopharyngeal carcinoma, but these therapies can not prevent the recurrence and metastasis of tumor cells. Furthermore, these therapies have severe side effects. Therefore, it is important to find a more effective therapy, e. g., a gene therapy for treatment of nasopharyngeal carcinoma. Cecropin AD （Cad） is a hybrid peptide that exhibits higher antibacterial activity than natural cecropin. It consists of 1-11 amino acid residues in the N-end of cecropin A and 12-37 amino acid residues in the c-end of cecropin D. The role of Cad in the malignant cells remains unclear. In this study, the Cad gene was cloned and transferred into NPC CNE2 cells and its pro-apoptotic effect were investigated.

关键词： cecropin AD nasopharyngeal carcinoma CNE2 cells apoptosis

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High-performance fiber-integrated multifunctional graphene-optoelectronic device with photoelectric detection and optic-phase modulation

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Photonics research 2020年第12期8卷 1949-1957页

作者： LINQING ZHUO PENGPENG FAN SHUANG ZHANG YUANSONG ZHAN YANMEI LINYU ZHANG DONGQUAN LI ZHEN CHE WENGUO ZHU HUADAN ZHENG JIEYUAN TANG JUN ZHANG YONGCHUN ZHONG WENXIAO FANG GUOGUANG LU JIANHUI YU ZHE CHEN Key Laboratory of Optoelectronic Information and Sensing Technologies of Guangdong Higher Education Institutes Department of Optoelectronic EngineeringJinan UniversityGuangzhou 510632China Engineering research center on Visible Light Communication of Guangdong Province Department of Optoelectronic EngineeringJinan UniversityGuangzhou 510632China Key Laboratory of Visible Light Communications of guangzhou Jinan UniversityGuangzhou 510632China Science and Technology on Reliability Physics and Application of Electronic Component Laboratory China Electronic Product Reliability and Environmental Testing Research InstituteGuangzhou 510610China

In graphene-based optoelectronic devices,the ultraweak interaction between a light and monolayer graphene leads to low optical absorption and low responsivity for the photodetectors and relative high half-wave voltage for the phase ***,an integration of the monolayer graphene onto the side-polished optical fiber is demonstrated,which is capable of providing a cost-effective strategy to enhance the light–graphene interaction,allowing us to obtain a highly efficient optical absorption in graphene and achieve multifunctions:photodetection and optical phase *** a photodetector,the device has ultrahigh responsivity(1.5×10^(7) A/W)and high external quantum efficiency(>1.2×10^(9)%).Additionally,the polybutadiene/polymethyl methacrylate(PMMA)film on the graphene can render the device an optical phase modulator through the large thermo-optic effect of the *** a phase modulator,the device has a relatively low half-wave voltage of 3 V with a 16 dB extinction ratio in Mach–Zehnder interferometer configuration.

关键词： optoelectronic fiber modulator

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Novel insights into stress-induced susceptibility to influenza:corticosterone impacts interferon-βresponses by Mfn2-mediated ubiquitin degradation of MAVS

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Signal Transduction and Targeted Therapy 2020年第1期5卷 782-793页

作者： Zhuo Luo Li-Fang Liu Ying-Nan Jiang Lu-Ping Tang Wen Li Shu-Hua Ouyang Long-Fang Tu Yan-Ping Wu Hai-Biao Gong Chang-Yu Yan Shan Jiang Yu-Hui Lu Tongzheng Liu Zhenyou Jiang Hiroshi Kurihara Yang Yu Xin-Sheng Yao Yi-Fang Li Rong-Rong He Guangdong Engineering research center of Chinese Medicine&Disease Susceptibility Jinan UniversityGuangzhou 510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs research College of PharmacyJinan UniversityGuangzhou 510632China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China Institute of Tumor Pharmacology College of PharmacyJinan UniversityGuangzhou 510632China Department of Microbiology and Immunology Basic Medicine CollegeJinan UniversityGuangZhou 510632China

Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains *** this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung ***(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed *** further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in ***,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in ***,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this ***-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of ***-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.

关键词： influenza ubiquitin MAVS

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