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| 1 | In vivo self-assembled small RNAs as a new generation of RNAi therapeutics显示文摘RNAi therapy has undergone two stages of development,direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands;both have not solved the problem of efficient in vivo siRNA delivery.Here,we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes.By combination of different genetic circuit modules,in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues(e.g.,brain),inducing potent target gene silencing in these tissues.The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases,including EGFR/KRAS in lung cancer,EGFR/TNC in glioblastoma and PTP1B in obesity.Overall,our strategy represents a next generation RNAi therapeutics,which makes RNAi therapy feasible. | Zheng Fu Xiang Zhang Xinyan Zhou Uzair Ur-Rehman Mengchao Yu Hongwei Liang Hongyuan Guo Xu Guo Yan Kong Yuanyuan Su Yangyang Ye Xiuting Hu Wei Cheng Jinrong Wu Yanbo Wang Yayun Gu Sheng-feng Lu Dianqing Wu Ke Zen Jing Li Chao Yan Chen-Yu Zhang Xi Chen | 2021 | Cell Research2021，31，6： | 10 |
| 2 | U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population显示文摘在由维持 chromosomal 正直并且阻止染色体的生物变老的一个关键角色结束的 Telomeres 玩熔化。流行病学的研究建议了 telomere 长度的内部个人的差别能影响倾向到多重癌症,但是关于食道的有鳞的房间癌(ESCC ) 的证据仍然是不明确的。几 telomere 在白种人的长度相关的单个核苷酸多型性(TLSNP ) 在染色体宽的协会研究被报导了。然而,在 ESCC 开发的 telomere 长度和 TL-SNPs 的效果是不清楚的。因此,我们进行了盒子控制研究(1045 个 ESCC 案例和 1433 控制) 在中国人口评估在 telomere 长度, TL-SNPs,和 ESCC 风险之间的协会。作为结果, ESCC 案例显示出全面更短的相对 telomere 长度(RTL )( 中部:1.34 ) 比控制(中部:1.50, P < 0.001 ) 。更有趣地,一个明显的非线性的U字形的协会在 RTL 和 ESCC 风险之间被观察( P < 0.001 )与比率(95%信心间隔)等于到 2.40 的机会( 1.843.14 ), 1.36 ( 1.031.79 ), 1.01 ( 0.761.35 ),并且 1.37 ( 1.031.82 )为个人在第一(最短),第二,第三,并且 第5 (最长) quintile 分别地,在是的 第4 quintile 与那些相比引用组。没有重要协会在八报导 TL-SNPs 和 ESCC 危险性之间被观察。这些调查结果建议短或极其长的 telomeres 可以是为在中国人口的 ESCC 的风险因素。 | Jiangbo Du Wenjie Xue Yong Ji Xun Zhu Yayun Gu Meng Zhu Cheng Wang Yong Gao Juncheng Dai Hongxia Ma Yue Jiang Jiaping Chen Zhibin Hu Guangfu Jin Hongbing Shen | 2015 | Frontiers of Medicine2015，9，4： | 4 |
| 3 | Stable Lithium-Carbon Composite Enabled by Dual-Salt Additives显示文摘Lithium metal is regarded as the ultimate negative electrode material for secondary batteries due to its high energy density.However,it suffers from poor cycling stability because of its high reactivity with liquid electrolytes.Therefore,continuous efforts have been put into improving the cycling Coulombic efficiency(CE)to extend the lifespan of the lithium metal negative electrode.Herein,we report that using dual-salt additives of LiPF_(6) and LiNO_(3) in an ether solvent-based electrolyte can significantly improve the cycling stability and rate capability of a Li-carbon(Li-CNT)composite.As a result,an average cycling CE as high as 99.30% was obtained for the Li-CNT at a current density of 2.5 mA cm^(-2) and an negative electrode to positive electrode capacity(N/P)ratio of 2.The cycling stability and rate capability enhancement of the Li-CNT negative electrode could be attributed to the formation of a better solid electrolyte interphase layer that contains both inorganic components and organic polyether.The former component mainly originates from the decomposition of the LiNO_(3) additive,while the latter comes from the LiPF_(6)-induced ring-opening polymerization of the ether solvent.This novel surface chemistry significantly improves the CE of Li negative electrode,revealing its importance for the practical application of lithium metal batteries. | Lei Zheng Feng Guo Tuo Kang Yingzhu Fan Wei Gu Yayun Mao Ya Liu Rong Huang Zhiyun Li Yanbin Shen Wei Lu Liwei Chen | 2021 | Nano-Micro Letters2021，13，7： | 3 |
| 4 | The cancer-testis gene,MEIOB,sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency显示文摘Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC. | Yayun Gu Cheng Wang Rongxuan Zhu Jianshui Yang Wenwen Yuan Yanhui Zhu Yan Zhou Na Qin Hongbing Shen Hongxia Ma Hongxia Wang Xiaoan Liu Zhibin Hu | 2021 | Cancer Biology & Medicine2021，18，1： | 2 |
| 5 | Trimethoxyboroxine as an electrolyte additive to enhance the 4.5V cycling performance of a Ni-rich layered oxide cathode显示文摘Ni-rich layered oxides are attractive cathode materials for advanced lithium-ion batteries(LIBs)due to their high energy density.However,their large-scale application is seriously hindered by their interfacial instability,especially at a high cut-off potential.Here,we demonstrate that trimethoxyboroxine(TMOBX)is an effective film-forming additive to address the interfacial instability of LiNi0.8Co0.1Mn0.1O_(2)(NCM811)material at a high cut-off voltage of 4.5V.We find that TMOBX decomposes before carbonate solvent and forms a thin cathode electrolyte interphase(CEI)layer on the surface of the NCM811 material.This TMOBX-formed CEI significantly suppresses electrolyte decomposition at a high potential and inhibits the dissolution of transition metals from NCM811 during cycling.In addition,electron-deficient borate compounds coordinate with anions(PF6^(−),F^(-) etc.)and H2O in the battery,further improving the battery's stability.As a result,adding 1.0wt%of TMOBX boosts the capacity retention of a Li||NCM811cell from 68.72%to 86.60%after 200 cycles at 0.5C in the range of 2.8–4.5V. | Wei Gu Guoyong Xue Qingyu Dong Ruowei Yi Yayun Mao Lei Zheng Haikuo Zhang Xiulin Fan Yanbin Shen Liwei Chen | 2022 | eScience2022，2，5： | 1 |
| 6 | Gene amplification-driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A-YTHDF2-dependent in lung adenocarcinoma显示文摘Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reasons for activation of KIAA1429(also known as VIRMA,an RNA methyltransferase)and its underlying mechanism in lung adenocarcinoma(LUAD)remain largely unexplored.In this study,we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.Methods:Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase.The in vitro and in vivo functions of KIAA1429 were investigated.Transcriptome sequencing,methylated RNA immunoprecipitation sequencing(MeRIP-seq),m6A dot blot assays and RNA immunoprecipitation(RIP)were performed to confirm the modified gene mediated by KIAA1429.RNA stability assays were used to detect the half-life of the target gene.Results:Copy number amplification drove higher expression of KIAA1429 in LUAD,whichwas correlatedwith poor overall survival.Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD.Mechanistically,the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays.We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner.Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA,leading to enhanced YTH m6A RNA binding protein 2(YTHDF2,the m6A“reader”)-dependent BTG2 mRNA stability and promoted the expression of BTG2;thus,participating in the tumorigenesis of LUAD.Conclusions:Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis,which may provide a novel view on the targeted molecular therapy of LUAD. | Chang Zhang Qi Sun Xu Zhang Na Qin Zhening Pu Yayun Gu Caiwang Yan Meng Zhu Juncheng Dai ChengWang Ni Li Guangfu Jin Hongxia Ma Zhibin Hu Erbao Zhang Fengwei Tan Hongbing Shen | 2022 | Cancer Communications2022，42，7： | 1 |
| 7 | Feasibility and physics potential of detecting ^(8)B solar neutrinos at JUNO显示文摘The Jiangmen Underground Neutrino Observatory(JUNO)features a 20 kt multi-purpose underground liquid scintillator sphere as its main detector.Some of JUNO's features make it an excellent location for^8B solar neutrino measurements,such as its low-energy threshold,high energy resolution compared with water Cherenkov detectors,and much larger target mass compared with previous liquid scintillator detectors.In this paper,we present a comprehensive assessment of JUNO's potential for detecting^8B solar neutrinos via the neutrino-electron elastic scattering process.A reduced 2 MeV threshold for the recoil electron energy is found to be achievable,assuming that the intrinsic radioactive background^(238)U and^(232)Th in the liquid scintillator can be controlled to 10^(-17)g/g.With ten years of data acquisition,approximately 60,000 signal and 30,000 background events are expected.This large sample will enable an examination of the distortion of the recoil electron spectrum that is dominated by the neutrino flavor transformation in the dense solar matter,which will shed new light on the inconsistency between the measured electron spectra and the predictions of the standard three-flavor neutrino oscillation framework.IfDelta m^(2)_(21)=4.8times10^(-5);(7.5times10^(-5))eV^(2),JUNO can provide evidence of neutrino oscillation in the Earth at approximately the 3sigma(2sigma)level by measuring the non-zero signal rate variation with respect to the solar zenith angle.Moreover,JUNO can simultaneously measureDelta m^2_(21)using^8B solar neutrinos to a precision of 20% or better,depending on the central value,and to sub-percent precision using reactor antineutrinos.A comparison of these two measurements from the same detector will help understand the current mild inconsistency between the value of Delta m^2_(21)reported by solar neutrino experiments and the KamLAND experiment. | Angel Abusleme Thomas Adam Shakeel Ahmad Sebastiano Aiello Muhammad Akram Nawab Ali Fengpeng An Guangpeng An Qi An Giuseppe Andronico Nikolay Anfimov Vito Antonelli Tatiana Antoshkina Burin Asavapibhop João Pedro Athayde Marcondes de André Didier Auguste Andrej Babic Wander Baldini Andrea Barresi Eric Baussan Marco Bellato Antonio Bergnoli Enrico Bernieri David Biare Thilo Birkenfeld Sylvie Blin David Blum Simon Blyth Anastasia Bolshakova Mathieu Bongrand Clément Bordereau Dominique Breton Augusto Brigatti Riccardo Brugnera Riccardo Bruno Antonio Budano Max Buesken Mario Buscemi Jose Busto Ilya Butorov Anatael Cabrera Hao Cai Xiao Cai Yanke Cai Zhiyan Cai Antonio Cammi Agustin Campeny Chuanya Cao Guofu Cao Jun Cao Rossella Caruso Cédric Cerna Jinfan Chang Yun Chang Pingping Chen Po-An Chen Shaomin Chen Shenjian Chen Xurong Chen Yi-Wen Chen Yixue Chen Yu Chen Zhang Chen Jie Cheng Yaping Cheng Alexander Chepurnov Davide Chiesa Pietro Chimenti Artem Chukanov Anna Chuvashova Gérard Claverie Catia Clementi Barbara Clerbaux Selma Conforti Di Lorenzo Daniele Corti Salvatore Costa Flavio Dal Corso Christophe De La Taille Jiawei Deng Zhi Deng Ziyan Deng Wilfried Depnering Marco Diaz Xuefeng Ding Yayun Ding Bayu Dirgantara Sergey Dmitrievsky Tadeas Dohnal Georgy Donchenko Jianmeng Dong Damien Dornic Evgeny Doroshkevich Marcos Dracos Frédéric Druillole Shuxian Du Stefano Dusini Martin Dvorak Timo Enqvist Heike Enzmann Andrea Fabbri Lukas Fajt Donghua Fan Lei Fan Can Fang Jian Fang Marco Fargetta Anna Fatkina Dmitry Fedoseev Vladko Fekete Li-Cheng Feng Qichun Feng Richard Ford Andrey Formozov Amélie Fournier Haonan Gan Feng Gao Alberto Garfagnini Alexandre Göttel Christoph Genster Marco Giammarchi Agnese Giaz Nunzio Giudice Franco Giuliani Maxim Gonchar Guanghua Gong Hui Gong Oleg Gorchakov Yuri Gornushkin Marco Grassi Christian Grewing Maxim Gromov Vasily Gromov Minghao Gu Xiaofei Gu Yu Gu Mengyun Guan Nunzio Guardone Maria Gul Cong Guo Jingyuan Guo Wanlei Guo Xinheng Guo Yuhang Guo Paul Hackspacher Caren Hagner Ran Han Yang Han Miao He Wei He Tobias Heinz Patrick Hellmuth Yuekun Heng Rafael Herrera Daojin Hong YuenKeung Hor Shaojing Hou Yee Hsiung Bei-Zhen Hu Hang Hu Jianrun Hu Jun Hu Shouyang Hu Tao Hu Zhuojun Hu Chunhao Huang Guihong Huang Hanxiong Huang Qinhua Huang Wenhao Huang Xingtao Huang Yongbo Huang Jiaqi Hui Wenju Huo Cédric Huss Safeer Hussain Antonio Insolia Ara Ioannisian Daniel Ioannisyan Roberto Isocrate Kuo-Lun Jen Xiaolu Ji Xingzhao Ji Huihui Jia Junji Jia Siyu Jian Di Jiang Xiaoshan Jiang Ruyi Jin Xiaoping Jing Cécile Jollet Jari Joutsenvaara Sirichok Jungthawan Leonidas Kalousis Philipp Kampmann Li Kang Michael Karagounis Narine Kazarian Amir Khan Waseem Khan Khanchai Khosonthongkee Patrick Kinz Denis Korablev Konstantin Kouzakov Alexey Krasnoperov Svetlana Krokhaleva Zinovy Krumshteyn Andre Kruth Nikolay Kutovskiy Pasi Kuusiniemi Tobias Lachenmaier Cecilia Landini Sébastien Leblanc Frederic Lefevre Liping Lei Ruiting Lei Rupert Leitner Jason Leung Demin Li Fei Li Fule Li Haitao Li Huiling Li Jiaqi Li Jin Li Kaijie Li Mengzhao Li Nan Li Nan Li Qingjiang Li Ruhui Li Shanfeng Li Shuaijie Li Tao Li Weidong Li Weiguo Li Xiaomei Li Xiaonan Li Xinglong Li Yi Li Yufeng Li Zhibing Li Ziyuan Li Hao Liang Hao Liang Jingjing Liang Jiajun Liao Daniel Liebau Ayut Limphirat Sukit Limpijumnong Guey-Lin Lin Shengxin Lin Tao Lin Jiajie Ling Ivano Lippi Fang Liu Haidong Liu Hongbang Liu Hongjuan Liu Hongtao Liu Hu Liu Hui Liu Jianglai Liu Jinchang Liu Min Liu Qian Liu Qin Liu Runxuan Liu Shuangyu Liu Shubin Liu Shulin Liu Xiaowei Liu Yan Liu Alexey Lokhov Paolo Lombardi Claudio Lombardo Kai Loo Chuan Lu Haoqi Lu Jingbin Lu Junguang Lu Shuxiang Lu Xiaoxu Lu Bayarto Lubsandorzhiev Sultim Lubsandorzhiev Livia Ludhova Fengjiao Luo Guang Luo Pengwei Luo Shu Luo Wuming Luo Vladimir Lyashuk Qiumei Ma Si Ma Xiaoyan Ma Xubo Ma Jihane Maalmi Yury Malyshkin Fabio Mantovani Francesco Manzali Xin Mao Yajun Mao Stefano MMari Filippo Marini Sadia Marium Cristina Martellini Gisele Martin-Chassard Agnese Martini Davit Mayilyan Axel Müller Ints Mednieks Yue Meng Anselmo Meregaglia Emanuela Meroni David Meyhöfer Mauro Mezzetto Jonathan Miller Lino Miramonti Salvatore Monforte Paolo Montini Michele Montuschi Nikolay Morozov Pavithra Muralidharan Massimiliano Nastasi Dmitry VNaumov Elena Naumova Igor Nemchenok Alexey Nikolaev Feipeng Ning Zhe Ning Hiroshi Nunokawa Lothar Oberauer Juan Pedro Ochoa-Ricoux Alexander Olshevskiy Domizia Orestano Fausto Ortica Hsiao-Ru Pan Alessandro Paoloni Nina Parkalian Sergio Parmeggiano Teerapat Payupol Yatian Pei Nicomede Pelliccia Anguo Peng Haiping Peng Frédéric Perrot Pierre-Alexandre Petitjean Fabrizio Petrucci Luis Felipe Piñeres Rico Oliver Pilarczyk Artyom Popov Pascal Poussot Wathan Pratumwan Ezio Previtali Fazhi Qi Ming Qi Sen Qian Xiaohui Qian Hao Qiao Zhonghua Qin Shoukang Qiu Muhammad Rajput Gioacchino Ranucci Neill Raper Alessandra Re Henning Rebber Abdel Rebii Bin Ren Jie Ren Taras Rezinko Barbara Ricci Markus Robens Mathieu Roche Narongkiat Rodphai Aldo Romani Bedřich Roskovec Christian Roth Xiangdong Ruan Xichao Ruan Saroj Rujirawat Arseniy Rybnikov Andrey Sadovsky Paolo Saggese Giuseppe Salamanna Simone Sanfilippo Anut Sangka Nuanwan Sanguansak Utane Sawangwit Julia Sawatzki Fatma Sawy Michaela Schever Jacky Schuler Cédric Schwab Konstantin Schweizer Dmitry Selivanov Alexandr Selyunin Andrea Serafini Giulio Settanta Mariangela Settimo Muhammad Shahzad Vladislav Sharov Gang Shi Jingyan Shi Yongjiu Shi Vitaly Shutov Andrey Sidorenkov FedorŠimkovic Chiara Sirignano Jaruchit Siripak Monica Sisti Maciej Slupecki Mikhail Smirnov Oleg Smirnov Thiago Sogo-Bezerra Julanan Songwadhana Boonrucksar Soonthornthum Albert Sotnikov Ondrej Sramek Warintorn Sreethawong Achim Stahl Luca Stanco Konstantin Stankevich DušanŠtefánik Hans Steiger Jochen Steinmann Tobias Sterr Matthias Raphael Stock Virginia Strati Alexander Studenikin Gongxing Sun Shifeng Sun Xilei Sun Yongjie Sun Yongzhao Sun Narumon Suwonjandee Michal Szelezniak Jian Tang Qiang Tang Quan Tang Xiao Tang Alexander Tietzsch Igor Tkachev Tomas Tmej Konstantin Treskov Andrea Triossi Giancarlo Troni Wladyslaw Trzaska Cristina Tuve Stefan van Waasen Johannes van den Boom Guillaume Vanroyen Nikolaos Vassilopoulos Vadim Vedin Giuseppe Verde Maxim Vialkov Benoit Viaud Cristina Volpe Vit Vorobel Lucia Votano Pablo Walker Caishen Wang Chung-Hsiang Wang En Wang Guoli Wang Jian Wang Jun Wang Kunyu Wang Lu Wang Meifen Wang Meng Wang Ruiguang Wang Siguang Wang Wei Wang Wenshuai Wang Xi Wang Xiangyue Wang Yangfu Wang Yaoguang Wang Yi Wang Yifang Wang Yuanqing Wang Yuman Wang Zhe Wang Zheng Wang Zhimin Wang Zongyi Wang Apimook Watcharangkool Lianghong Wei Wei Wei Yadong Wei Liangjian Wen Christopher Wiebusch Steven Chan-Fai Wong Bjoern Wonsak Diru Wu Fangliang Wu Qun Wu Wenjie Wu Zhi Wu Michael Wurm Jacques Wurtz Christian Wysotzki Yufei Xi Dongmei Xia Yuguang Xie Zhangquan Xie Zhizhong Xing Benda Xu Donglian Xu Fanrong Xu Jilei Xu Jing Xu Meihang Xu Yin Xu Yu Xu Baojun Yan Xiongbo Yan Yupeng Yan Anbo Yang Changgen Yang Huan Yang Jie Yang Lei Yang Xiaoyu Yang Yifan Yang Haifeng Yao Zafar Yasin Jiaxuan Ye Mei Ye Ugur Yegin Frédéric Yermia Peihuai Yi Xiangwei Yin Zhengyun You Boxiang Yu Chiye Yu Chunxu Yu Hongzhao Yu Miao Yu Xianghui Yu Zeyuan Yu Chengzhuo Yuan Ying Yuan Zhenxiong Yuan Ziyi Yuan Baobiao Yue Noman Zafar Andre Zambanini Pan Zeng Shan Zeng Tingxuan Zeng Yuda Zeng Liang Zhan Feiyang Zhang Guoqing Zhang Haiqiong Zhang Honghao Zhang Jiawen Zhang Jie Zhang Jingbo Zhang Peng Zhang Qingmin Zhang Shiqi Zhang Tao Zhang Xiaomei Zhang Xuantong Zhang Yan Zhang Yinhong Zhang Yiyu Zhang Yongpeng Zhang Yuanyuan Zhang Yumei Zhang Zhenyu Zhang Zhijian Zhang Fengyi Zhao Jie Zhao Rong Zhao Shujun Zhao Tianchi Zhao Dongqin Zheng Hua Zheng Minshan Zheng Yangheng Zheng Weirong Zhong Jing Zhou Li Zhou Nan Zhou Shun Zhou Xiang Zhou Jiang Zhu Kejun Zhu Honglin Zhuang Liang Zong Jiaheng Zou | 2021 | Chinese Physics C2021，45，2： | 0 |
| 8 | A causal variant rs3769823 in 2q33.1 involved in apoptosis pathway leading to a decreased risk of non-small cell lung cancer显示文摘Objective:Although our previous genome-wide association study(GWAS)has identified chromosome 2q33.1 as a susceptibility locus for non-small cell lung cancer(NSCLC),the causal variants remain unclear.The aims of this study were to identify the causal variants in 2q33.1 and to explore their biological functions in NSCLC.Methods:CCK-8,colony formation,EdU incorporation,Transwell,and quantitative real-time polymerase chain reaction assays were applied to examine variant function.The tumor xenograft model was used to examine variant function in vivo.Caspase-8 activity assays,flow cytometry analysis,and co-immunoprecipitation assays were used to explore the molecular mechanism.Results:The missense variant rs3769823(A>G),which caused the substitution of lysine with arginine at amino acid 14 in caspase-8(caspase-8K14R),was identified as a potential causal candidate in 2q33.1.Compared with the wild type caspase-8(caspase8WT)group,the caspase-8K14R group had higher expression of caspase-8 and cleaved caspase-8.Caspase-8K14R inhibited the proliferation and metastasis of human lung cancer cell lines in vitro.Moreover,caspase-8K14R repressed lung cancer cell growth in vivo.Mechanistically,caspase-8K14R was more sensitive than caspase-8WT to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-mediated apoptosis and showed higher binding of caspase-8 and FADD.Conclusions:These results suggested that rs3769823 is the causal variant in chromosome 2q33.1 and is involved in an apoptosis pathway,leading to a decreased risk of NSCLC. | Xu Zhang Na Qin Jingyi Fan Chang Zhang Qi Sun Yayun Gu Meng Zhu Erbao Zhang Juncheng Dai Guangfu Jin Hongxia Ma Zhibin Hu Hongbing Shen | 2022 | Cancer Biology & Medicine2022，19，9： | 0 |
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