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152. The OsEIL1‐OsERF115‐target gene regulatory module controls grain size and weight in rice

Author

Liu, Chang, primary, Ma, Tian, additional, Yuan, Dingyang, additional, Zhou, Yang, additional, Long, Yan, additional, Li, Ziwen, additional, Dong, Zhenying, additional, Duan, Meijuan, additional, Yu, Dong, additional, Jing, Yizhi, additional, Bai, Xiaoyue, additional, Wang, Yanbo, additional, Hou, Quancan, additional, Liu, Shuangshuang, additional, Zhang, Jin‐Song, additional, Chen, Shou‐Yi, additional, Li, Dayong, additional, Liu, Xue, additional, Li, Zhikang, additional, Wang, Wensheng, additional, Li, Jinping, additional, Wei, Xun, additional, Ma, Biao, additional, and Wan, Xiangyuan, additional

Published
2022
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155. Thoracic aortic computed tomography angiography in swine: establishment of a baseline for endovascular evaluation of the ascending aorta

Author

Li Yiming, Xu Ding, Xu Ziyi, Zhao Yuxi, Zeng Zhaoxiang, Feng Jiaxuan, Li Ziwen, Zhou Jian, Feng Rui, Wu Mingwei, Jing Zai-ping, Bao Xianhao, and Li Tao

Subjects
Male, Pulmonary and Respiratory Medicine, Computed Tomography Angiography, Swine, Aorta, Thoracic, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Left coronary artery, medicine.artery, Ascending aorta, Medical imaging, Animals, Medicine, Thoracic aorta, Aorta, Computed tomography angiography, medicine.diagnostic_test, business.industry, Endovascular Procedures, Disease Models, Animal, Ostium, 030220 oncology & carcinogenesis, Angiography, Female, Stents, Surgery, Cardiology and Cardiovascular Medicine, business, Nuclear medicine
Abstract

OBJECTIVESOur goal was to establish a baseline of computed tomography (CT) angiographic data for the porcine ascending thoracic aorta for endovascular evaluation of animal experiments and device development.METHODSThoracic aortic CT angiography was conducted on 49 pigs with an average body weight of 60–65 kg. The CT angiographic scans were done on an imaging reconstruction workstation to obtain the specific aortic geometric data, including the diameters of the planes, the heights among the planes and the clock positions of target arteries.RESULTSFourteen important planes were defined in the study for endograft customizing reference. The diameters of the planes were measured, and the heights among the planes were recorded. For endograft fenestrations, the right coronary artery ostium clock position was 100.11 ± 7.29°, and the brachiocephalic trunk ostium clock position was 74.72 ± 6.45°. The best projection angle of the tangent position of the left coronary artery was the right anterior oblique 17 ± 7° position. A pig with a rare congenital giant dilated aorta was found among the candidate experimental animals.CONCLUSIONSFor experimental porcine models, CT angiography has proved to be a suitable imaging technique. The established baseline angiography of the swine can provide reference values for future animal experiments and device development.

Published
2020

158. Prognostic Value of Coronary CT Angiography-Derived Fractional Flow Reserve in Non-obstructive Coronary Artery Disease: A Prospective Multicenter Observational Study

Author

Zhou, Fan, primary, Chen, Qian, additional, Luo, Xiao, additional, Cao, Wei, additional, Li, Ziwen, additional, Zhang, Bo, additional, Schoepf, U. Joseph, additional, Gill, Callum E., additional, Guo, Lili, additional, Gao, Hong, additional, Li, Qingyao, additional, Shi, Yibing, additional, Tang, Tingting, additional, Liu, Xiaochen, additional, Wu, Honglin, additional, Wang, Dongqing, additional, Xu, Feng, additional, Jin, Dongsheng, additional, Huang, Sheng, additional, Li, Haige, additional, Pan, Changjie, additional, Gu, Hongmei, additional, Xie, Lixiang, additional, Wang, Ximing, additional, Ye, Jing, additional, Jiang, Jianwei, additional, Zhao, Hanqing, additional, Fang, Xiangming, additional, Xu, Yi, additional, Xing, Wei, additional, Li, Xiaohu, additional, Yin, Xindao, additional, Lu, Guang Ming, additional, and Zhang, Long Jiang, additional

Published
2022
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165. Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma

Author

Cun, Yixian, primary, An, Sanqi, additional, Zheng, Haiqing, additional, Lan, Jing, additional, Chen, Wenfang, additional, Luo, Wanjun, additional, Yao, Chengguo, additional, Li, Xincheng, additional, Huang, Xiang, additional, Sun, Xiang, additional, Wu, Zehong, additional, Hu, Yameng, additional, Li, Ziwen, additional, Zhang, Shuxia, additional, Wu, Geyan, additional, Yang, Meisongzhu, additional, Tang, Miaoling, additional, Yu, Ruyuan, additional, Liao, Xinyi, additional, Gao, Guicheng, additional, Zhao, Wei, additional, Wang, Jinkai, additional, and Li, Jun, additional

Published
2021
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170. Multi-species meta-analysis identifies transcriptional signatures associated with cardiac endothelial responses in the ischaemic heart.

Author

Li, Ziwen, Solomonidis, Emmanouil G, Berkeley, Bronwyn, Tang, Michelle Nga Huen, Stewart, Katherine Ross, Perez-Vicencio, Daniel, McCracken, Ian R, Spiroski, Ana-Mishel, Gray, Gillian A, Barton, Anna K, Sellers, Stephanie L, Riley, Paul R, Baker, Andrew H, and Brittan, Mairi

Subjects
*VASCULAR endothelial cells, *ENDOTHELIAL cells, *HEART, *REGULATOR genes, *MYOCARDIAL infarction
Abstract

Aim Myocardial infarction remains the leading cause of heart failure. The adult human heart lacks the capacity to undergo endogenous regeneration. New blood vessel growth is integral to regenerative medicine necessitating a comprehensive understanding of the pathways that regulate vascular regeneration. We sought to define the transcriptomic dynamics of coronary endothelial cells following ischaemic injuries in the developing and adult mouse and human heart and to identify new mechanistic insights and targets for cardiovascular regeneration. Methods and results We carried out a comprehensive meta-analysis of integrated single-cell RNA-sequencing data of coronary vascular endothelial cells from the developing and adult mouse and human heart spanning healthy and acute and chronic ischaemic cardiac disease. We identified species-conserved gene regulatory pathways aligned to endogenous neovascularization. We annotated injury-associated temporal shifts of the endothelial transcriptome and validated four genes: VEGF-C, KLF4, EGR1, and ZFP36. Moreover, we showed that ZFP36 regulates human coronary endothelial cell proliferation and defined that VEGF-C administration in vivo enhances clonal expansion of the cardiac vasculature post-myocardial infarction. Finally, we constructed a coronary endothelial cell meta-atlas, CrescENDO, to empower future in-depth research to target pathways associated with coronary neovascularization. Conclusion We present a high-resolution single-cell meta-atlas of healthy and injured coronary endothelial cells in the mouse and human heart, revealing a suite of novel targets with great potential to promote vascular regeneration, and providing a rich resource for therapeutic development. [ABSTRACT FROM AUTHOR]

Published
2023
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172. Single-cell RNA sequencing profiling of mouse endothelial cells in response to pulmonary arterial hypertension

Author

Rodor, Julie, primary, Chen, Shiau Haln, additional, Scanlon, Jessica P, additional, Monteiro, João P, additional, Caudrillier, Axelle, additional, Sweta, Sweta, additional, Stewart, Katherine Ross, additional, Shmakova, Alena, additional, Dobie, Ross, additional, Henderson, Beth E P, additional, Stewart, Kevin, additional, Hadoke, Patrick W F, additional, Southwood, Mark, additional, Moore, Stephen D, additional, Upton, Paul D, additional, Morrell, Nick W, additional, Li, Ziwen, additional, Chan, Stephen Y, additional, Handen, Adam, additional, Lafyatis, Robert, additional, de Rooij, Laura P M H, additional, Henderson, Neil C, additional, Carmeliet, Peter, additional, Spiroski, Ana Mishel, additional, Brittan, Mairi, additional, and Baker, Andrew H, additional

Published
2021
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175. Serine/arginine-rich splicing factor 7 plays oncogenic roles through specific regulation of m6A RNA modification

Author

Cun, Yixian, primary, An, Sanqi, additional, Zheng, Haiqing, additional, Lan, Jing, additional, Chen, Wenfang, additional, Luo, Wanjun, additional, Yao, Chengguo, additional, Li, Xincheng, additional, Huang, Xiang, additional, Sun, Xiang, additional, Wu, Zehong, additional, Hu, Yameng, additional, Li, Ziwen, additional, Zhang, Shuxia, additional, Wu, Geyan, additional, Yang, Meisongzhu, additional, Tang, Miaoling, additional, Yu, Ruyuan, additional, Liao, Xinyi, additional, Gao, Guicheng, additional, Zhao, Wei, additional, Wang, Jinkai, additional, and Li, Jun, additional

Published
2021
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178. MP60-02 TRANSCRIPTOMICS CAN PREDICT HOMOLOGOUS RECOMBINATION DEFICIENCY IN PROSTATE CANCER

Author

Weiner, Adam, primary, Liu, Yang, additional, McFarlane, Matthew, additional, Bawa, Pushpinder, additional, Li, Eric, additional, Zhao, Xin, additional, Li, Ziwen, additional, Hammoud, Tanya, additional, Hazime, Munna, additional, Karnes, R. Jeffrey, additional, Davicioni, Elai, additional, Reichert, Zachery, additional, Chinnaiyan, Arul, additional, Lotan, Tamara, additional, and Schaeffer, Edward, additional

Published
2021
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180. ZmMs33promotes anther elongation via modulating cell elongation regulators, metabolic homeostasis, and cell wall remodeling in maize

Author

Li, Ziwen, Zhu, Taotao, Liu, Shuangshuang, Zhao, Lina, An, Xueli, Long, Yan, Wei, Xun, Zhang, Juan, Dong, Zhenying, and Wan, Xiangyuan

Abstract

Plant cell elongation depends on well-defined gene regulations, adequate nutrients, and timely cell wall modifications. Anther size is positively correlated with the number and viability of pollen grains, while little is known about molecular mechanisms underlying anther cell elongation. Here, we found that properly activated cell elongation regulators at transcriptional levels in loss-of-function ZmMs33mutant (ms33-6038) anthers failed to promote maize anther elongation. ZmMs33deficiency disrupted metabolic homeostasis mainly by inhibiting both photosynthesis in anther endothecium and lipid accumulation in anther tapetum. Importantly, ms33-6038anthers displayed ectopic, premature and excessive secondary cell wall thickening in anther middle layer, which constrained cell elongation structurally and blocked nutrient flows across different anther wall layers. The metabolic disorder was only found in ms33-6038mutant rather than several representative male-sterility lines at transcriptional and post-translational levels. Collectively, the disordered metabolisms and blocked nutrient flows defeated the activated cell elongation regulators, and finally inhibited anther elongation and growth with a unique “idling effect” in ms33-6038mutant.

Published
2023
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181. Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction

Author

Li, Ziwen, Solomonidis, Emmanouil G, Meloni, Marco, Taylor, Richard S, Duffin, Rodger, Dobie, Ross, Magalhaes, Marlene S, Henderson, Beth E P, Louwe, Pieter A, D’Amico, Gabriela, Hodivala-Dilke, Kairbaan M, Shah, Ajay M, Mills, Nicholas L, Simons, Benjamin D, Gray, Gillian A, Henderson, Neil C, Baker, Andrew H, Brittan, Mairi, Simons, Benjamin [0000-0002-3875-7071], and Apollo - University of Cambridge Repository

Subjects
Neovascularization, Pathologic, Myocardium, Endothelial cells, Gene Expression Profiling, Therapeutic angiogenesis, Myocardial Infarction, Biology and Life Sciences, Neovascularization, Physiologic, Mice, Transgenic, Lineage tracing, Single-cell RNA sequencing, Myocardial infarction, Mice, Editor's Choice, Basic Science, Vascular Biology, Medicine and Health Sciences, Animals, Humans, Single-Cell Analysis, Cardiology and Cardiovascular Medicine, Transcriptome, Cell proliferation, Cells, Cultured
Abstract

Aims: A better understanding of the pathways that regulate regeneration of the coronary vasculature is of fundamental importance for the advancement of strategies to treat patients with heart disease. Here, we aimed to investigate the origin and clonal dynamics of endothelial cells (ECs) associated with neovascularization in the adult mouse heart following myocardial infarction (MI). Furthermore, we sought to define murine cardiac endothelial heterogeneity and to characterize the transcriptional profiles of pro-angiogenic resident ECs in the adult mouse heart, at single-cell resolution.Methods and results: An EC-specific multispectral lineage-tracing mouse (Pdgfb-iCreERT2-R26R-Brainbow2.1) was used to demonstrate that structural integrity of adult cardiac endothelium following MI was maintained through clonal proliferation by resident ECs in the infarct border region, without significant contributions from bone marrow cells or endothelial-to-mesenchymal transition. Ten transcriptionally discrete heterogeneous EC states, as well as the pathways through which each endothelial state is likely to enhance neovasculogenesis and tissue regeneration following ischaemic injury were defined. Plasmalemma vesicle-associated protein (Plvap) was selected for further study, which showed an endothelial-specific and increased expression in both the ischaemic mouse and human heart, and played a direct role in regulating human endothelial proliferation in vitro.Conclusion: We present a single-cell gene expression atlas of cardiac specific resident ECs, and the transcriptional hierarchy underpinning endogenous vascular repair following MI. These data provide a rich resource that could assist in the development of new therapeutic interventions to augment endogenous myocardial perfusion and enhance regeneration in the injured heart.

Published
2019

182. Numerical Simulation of CO 2 -ECBM Based on Multi-Physical Field Coupling Model.

Author

Li, Ziwen, Yu, Hongjin, and Bai, Yansong

Abstract

In this paper, heat injection and CO2 injection are combined, and the influence of coal seam parameters on CO2-ECBM is analyzed to improve the production of CH4 and CO2 reserves and the effective control of both greenhouse gases. A multi-physical field coupling model of CO2-ECBM was established based on Darcy's law, Fick's law of diffusion, the extended Langmuir model for adsorption, and the equation of state. Numerical simulation of CO2-ECBM under different coal seam parameters was carried out by COMSOL Multiphysics. The results show that increasing the injection pressure of the CO2 injection well and the initial pressure of the coal seam can effectively increase the gas pressure and concentration gradient, which has a positive effect on improving the extraction concentration of CH4 and the sequestration concentration of CO2 in the coal seam. The increase of the initial temperature of the coal seam will promote the desorption and diffusion of the binary elemental gas, resulting in a decrease in the concentration of coalbed methane and a decrease in the displacement effect. In the process of displacement, the greater the initial permeability, the greater the fracture opening of the coal seam, which is more conducive to the seepage transport of the gas. The closer to the position of the injection well, the better the displacement effect and the lower the permeability rate ratio. [ABSTRACT FROM AUTHOR]

Published
2022
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183. RNF219/ α ‐Catenin/LGALS3 Axis Promotes Hepatocellular Carcinoma Bone Metastasis and Associated Skeletal Complications

Author

Zhang, Shuxia, primary, Xu, Yingru, additional, Xie, Chan, additional, Ren, Liangliang, additional, Wu, Geyan, additional, Yang, Meisongzhu, additional, Wu, Xingui, additional, Tang, Miaoling, additional, Hu, Yameng, additional, Li, Ziwen, additional, Yu, Ruyuan, additional, Liao, Xinyi, additional, Mo, Shuang, additional, Wu, Jueheng, additional, Li, Mengfeng, additional, Song, Erwei, additional, Qi, Yanfei, additional, Song, Libing, additional, and Li, Jun, additional

Published
2021
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184. ZmFAR1 and ZmABCG26 Regulated by microRNA Are Essential for Lipid Metabolism in Maize Anther

Author

Jiang, Yilin, primary, Li, Ziwen, additional, Liu, Xinze, additional, Zhu, Taotao, additional, Xie, Ke, additional, Hou, Quancan, additional, Yan, Tingwei, additional, Niu, Canfang, additional, Zhang, Shaowei, additional, Yang, Mengbing, additional, Xie, Rongrong, additional, Wang, Jing, additional, Li, Jinping, additional, An, Xueli, additional, and Wan, Xiangyuan, additional

Published
2021
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185. A transcriptomic model for homologous recombination deficiency in prostate cancer

Author

Weiner, Adam B., primary, Liu, Yang, additional, McFarlane, Matthew, additional, Bawa, Pushpinder S., additional, Li, Eric V., additional, Zhao, Xin, additional, Li, Ziwen, additional, Hammoud, Tanya, additional, Hazime, Munna, additional, Karnes, R. Jeffrey, additional, Davicioni, Elai, additional, Reichert, Zachery R., additional, Chinnaiyan, Arul M., additional, Lotan, Tamara L., additional, Spratt, Daniel E., additional, and Schaeffer, Edward M., additional

Published
2021
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188. The influence of cultural exchange on international trade: an empirical test of Confucius Institutes based on China and the ‘Belt and Road’ areas

Author

Li, Qing, Han, Yonghui, Li, Ziwen, Wei, Dongming, Zhang, Fan, Li, Qing, Han, Yonghui, Li, Ziwen, Wei, Dongming, and Zhang, Fan

Abstract

With the implementation of the Belt and Road initiative, the development of trade governance between China and countries along the line has expanded. Firstly, this paper analyzes the impact of cultural exchanges through Confucius Institutes on regional trade cooperation from three dimensions: improving cultural identity, reducing trade costs and sharing information. Secondly, we utilise data trade data from the 64 countries along the line from 2004 to 2015 to examine the effects of Confucius Institutes in regional trade cooperation with China. Overall, we found that Confucius Institutes have significantly promoted the trade growth of China and those countries. Compared to exports, Confucius Institutes promote greater growth imports to the Belt and Road countries from China. Compared to countries in the Road, Confucius Institutes better promoted trade growth between China and countries in the Belt. This empirical conclusion stands under various robustness tests. Forth, after the 12th five-yearplan, the promoting effects of the Confucius Institute has been strengthening. Fifth, the smaller the cultural distance, the stronger the promoting effects of the Confucius Institute on the trade in BRI countries. However, the effect of language similarity is not significant. This study indicates that the Chinese government should pay more attention to the economic effects of cultural factors, such as the Confucius Institute, in policy design.

Published
2021

190. CRISPR/Cas9‐based discovery of maize transcription factors regulating male sterility and their functional conservation in plants

Author

Jiang, Yilin, primary, An, Xueli, additional, Li, Ziwen, additional, Yan, Tingwei, additional, Zhu, Taotao, additional, Xie, Ke, additional, Liu, Shuangshuang, additional, Hou, Quancan, additional, Zhao, Lina, additional, Wu, Suowei, additional, Liu, Xinze, additional, Zhang, Shaowei, additional, He, Wei, additional, Li, Fan, additional, Li, Jinping, additional, and Wan, Xiangyuan, additional

Published
2021
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192. The Loss-Function of the Male Sterile Gene ZmMs33 / ZmGPAT6 Results in Severely Oxidative Stress and Metabolic Disorder in Maize Anthers.

Author

Li, Ziwen, Liu, Shuangshuang, Zhu, Taotao, An, Xueli, Wei, Xun, Zhang, Juan, Wu, Suowei, Dong, Zhenying, Long, Yan, and Wan, Xiangyuan

Subjects
*OXIDATIVE stress, *MALE sterility in plants, *ANTHER, *METABOLIC disorders, *METABOLISM, *REACTIVE oxygen species, *CORN, *PLANT development
Abstract

In plants, oxidative stress and metabolic reprogramming frequently induce male sterility, however our knowledge of the underlying molecular mechanism is far from complete. Here, a maize genic male-sterility (GMS) mutant (ms33-6038) with a loss-of-function of the ZmMs33 gene encoding glycerol-3-phosphate acyltransferase 6 (GPAT6) displayed severe deficiencies in the development of a four-layer anther wall and microspores and excessive reactive oxygen species (ROS) content in anthers. In ms33-6038 anthers, transcriptome analysis identified thousands of differentially expressed genes that were functionally enriched in stress response and primary metabolism pathways. Further investigation revealed that 64 genes involved in ROS production, scavenging, and signaling were specifically changed in expression levels in ms33-6038 anthers compared to the other five investigated GMS lines. The severe oxidative stress triggered premature tapetal autophagy and metabolic reprogramming mediated mainly by the activated SnRK1-bZIP pathway, as well as the TOR and PP2AC pathways, proven by transcriptome analysis. Furthermore, 20 reported maize GMS genes were altered in expression levels in ms33-6038 anthers. The excessive oxidative stress and the metabolic reprogramming resulted in severe phenotypic deficiencies in ms33-6038 anthers. These findings enrich our understanding of the molecular mechanisms by which ROS and metabolic homeostasis impair anther and pollen development in plants. [ABSTRACT FROM AUTHOR]

Published
2022
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193. Single-cell RNA sequencing profiling of mouse endothelial cells in response to pulmonary arterial hypertension.

Author

Rodor, Julie, Chen, Shiau Haln, Scanlon, Jessica P, Monteiro, João P, Caudrillier, Axelle, Sweta, Sweta, Stewart, Katherine Ross, Shmakova, Alena, Dobie, Ross, Henderson, Beth E P, Stewart, Kevin, Hadoke, Patrick W F, Southwood, Mark, Moore, Stephen D, Upton, Paul D, Morrell, Nick W, Li, Ziwen, Chan, Stephen Y, Handen, Adam, and Lafyatis, Robert

Subjects
PULMONARY arterial hypertension, RNA sequencing, ENDOTHELIAL cells, MAJOR histocompatibility complex, MICE, HISTOCOMPATIBILITY class I antigens, SERINE/THREONINE kinases, PULMONARY hypertension
Abstract

Aims Endothelial cell (EC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterize EC dynamics in PAH at single-cell resolution. Methods and results We carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/hypoxia-induced PAH conditions. EC populations corresponding to distinct lung vessel types, including two discrete capillary populations, were identified in both Control and PAH mice. Differential gene expression analysis revealed global PAH-induced EC changes that were confirmed by bulk RNA-seq. This included upregulation of the major histocompatibility complex class II pathway, supporting a role for ECs in the inflammatory response in PAH. We also identified a PAH response specific to the second capillary EC population including upregulation of genes involved in cell death, cell motility, and angiogenesis. Interestingly, four genes with genetic variants associated with PAH were dysregulated in mouse ECs in PAH. To compare relevance across PAH models and species, we performed a detailed analysis of EC heterogeneity and response to PAH in rats and humans through whole-lung PAH scRNA-seq datasets, revealing that 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. We identified promising new candidates to target endothelial dysfunction including CD74, the knockdown of which regulates EC proliferation and barrier integrity in vitro. Finally, with an in silico cell ordering approach, we identified zonation-dependent changes across the arteriovenous axis in mouse PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and microvasculature. Conclusion This study uncovers PAH-induced EC transcriptomic changes at a high resolution, revealing novel targets for potential therapeutic candidate development. [ABSTRACT FROM AUTHOR]

Published
2022
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194. ZmMs25 encoding a plastid-localized fatty acyl reductase is critical for anther and pollen development in maize

Author

Zhang, Simiao, primary, Wu, Suowei, additional, Niu, Canfang, additional, Liu, Dongcheng, additional, Yan, Tingwei, additional, Tian, Youhui, additional, Liu, Shuangshuang, additional, Xie, Ke, additional, Li, Ziwen, additional, Wang, Yanbo, additional, Zhao, Wei, additional, Dong, Zhenying, additional, Zhu, Taotao, additional, Hou, Quancan, additional, Ma, Biao, additional, An, Xueli, additional, Li, Jinping, additional, and Wan, Xiangyuan, additional

Published
2021
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195. General Control Non-derepressible 1 (AtGCN1) Is Important for Flowering Time, Plant Growth, Seed Development, and the Transcription/Translation of Specific Genes in Arabidopsis

Author

Cui, Xiaona, primary, Gao, Kaili, additional, Wang, Linjuan, additional, Lv, Mengyang, additional, Li, Ziwen, additional, Zheng, Donghua, additional, Wu, Wenwu, additional, Yao, Wen, additional, Ding, Liying, additional, Li, Xiao, additional, Zhu, Jian-Kang, additional, and Zhang, Hairong, additional

Published
2021
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196. Dynamic structural remodeling of LINC01956 enhances temozolomide resistance in MGMT-methylated glioblastoma

Author

Liao, Xinyi, Zhang, Shuxia, Li, Xincheng, Qian, Wanying, Li, Man, Chen, Suwen, Wu, Xingui, Yu, Xuexin, Li, Ziwen, Tang, Miaoling, Xu, Yingru, Yu, Ruyuan, Zhang, Qiliang, Wu, Geyan, Zhang, Nu, Song, Libing, and Li, Jun

Abstract

The mechanisms underlying stimuli-induced dynamic structural remodeling of RNAs for the maintenance of cellular physiological function and survival remain unclear. Here, we showed that in MGMTpromoter–methylated glioblastoma (GBM), the RNA helicase DEAD-box helicase 46 (DDX46) is phosphorylated by temozolomide (TMZ)–activated checkpoint kinase 1 (CHK1), resulting in a dense-to-loose conformational change and an increase in DDX46 helicase activity. DDX46-mediated tertiary structural remodeling of LINC01956 exposes the binding motifs of LINC01956 to the 3′ untranslated region of O6-methylguanine DNA methyltransferase (MGMT). This accelerates recruitment of MGMTmRNA to the RNA export machinery and transportation of MGMTmRNA from the nucleus to the cytoplasm, leading to increased MGMT abundance and TMZ resistance. Using patient-derived xenograft (PDX) and tumor organoid models, we found that treatment with the CHK1 inhibitor SRA737abolishes TMZ-induced structural remodeling of LINC01956 and subsequent MGMT up-regulation, resensitizing TMZ-resistant MGMTpromoter–methylated GBM to TMZ. In conclusion, these findings highlight a mechanism underlying temozolomide-induced RNA structural remodeling and may represent a potential therapeutic strategy for patients with TMZ-resistant MGMTpromoter–methylated GBM.

Published
2024
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197. Transcriptomic Heterogeneity of Gleason Grade Group 5 Prostate Cancer.

Author

Kishan, Amar U, Kishan, Amar U, Romero, Tahmineh, Alshalalfa, Mohammed, Liu, Yang, Tran, Phuoc T, Nickols, Nicholas G, Ye, Huihui, Sajed, Dipti, Rettig, Matthew B, Reiter, Robert E, Garraway, Isla P, Spratt, Daniel E, Freedland, Steven J, Zhao, Xin, Li, Ziwen, Deek, Matthew, Livingstone, Julie, Mahal, Brandon A, Nguyen, Paul L, Feng, Felix Y, Den, Robert B, Schaeffer, Edward M, Lotan, Tamara L, Karnes, R Jeffrey, Klein, Eric A, Ross, Ashley E, Grogan, Tristan, Davicioni, Elai, Elashoff, David, Boutros, Paul C, Weidhaas, Joanne B, Kishan, Amar U, Kishan, Amar U, Romero, Tahmineh, Alshalalfa, Mohammed, Liu, Yang, Tran, Phuoc T, Nickols, Nicholas G, Ye, Huihui, Sajed, Dipti, Rettig, Matthew B, Reiter, Robert E, Garraway, Isla P, Spratt, Daniel E, Freedland, Steven J, Zhao, Xin, Li, Ziwen, Deek, Matthew, Livingstone, Julie, Mahal, Brandon A, Nguyen, Paul L, Feng, Felix Y, Den, Robert B, Schaeffer, Edward M, Lotan, Tamara L, Karnes, R Jeffrey, Klein, Eric A, Ross, Ashley E, Grogan, Tristan, Davicioni, Elai, Elashoff, David, Boutros, Paul C, and Weidhaas, Joanne B

Abstract

Gleason grade group (GG) 5 prostate cancer has been associated with an aggressive natural history, and retrospective data support a role for treatment intensification. However, clinical outcomes remain heterogeneous in this cohort, and intensified treatments carry an increased risk of adverse events. We sought to explore the transcriptomic heterogeneity of GG 5 tumors by querying transcriptomic data from the tumors of 2138 patients with GG 5 disease who underwent prostatectomy. Four distinct consensus clusters were identified with respect to differential transcriptional activation of hallmark pathways, with distinct molecular subtyping profiles and different average genomic risks (AGRs). One cluster, accounting for 325 tumors (15.2% of the population), was enriched for genes related to the cell cycle/proliferation, metabolic pathways, androgen response pathways, and DNA repair, and had a higher AGR than the other clusters (p < 0.001). This clustering, with an identification of a high genomic risk cluster, was subsequently validated in a separate cohort of 1921 patients as well as a third cohort of 201 patients. The latter cohort had outcomes available, and it was found that patients in the high genomic risk cluster had significantly worse distant metastasis-free survival than the other clusters. Tumors in this high genomic risk cluster of GG 5 disease may be particularly likely to benefit from treatment intensification. PATIENT SUMMARY: In this report, we examined differences in gene expression in tumors from men with Gleason grade group 5 prostate cancer. We identified significant diversity, with one specific subgroup of tumors associated with expression profiles that suggest a worse prognosis.

Published
2020

198. Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes

Author

Weiner, Adam B., primary, Vidotto, Thiago, additional, Liu, Yang, additional, Mendes, Adrianna A., additional, Salles, Daniela C., additional, Faisal, Farzana A., additional, Murali, Sanjana, additional, McFarlane, Matthew, additional, Imada, Eddie L., additional, Zhao, Xin, additional, Li, Ziwen, additional, Davicioni, Elai, additional, Marchionni, Luigi, additional, Chinnaiyan, Arul M., additional, Freedland, Stephen J., additional, Spratt, Daniel E., additional, Wu, Jennifer D., additional, Lotan, Tamara L., additional, and Schaeffer, Edward M., additional

Published
2021
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200. RNF219/α‐Catenin/LGALS3 Axis Promotes Hepatocellular Carcinoma Bone Metastasis and Associated Skeletal Complications

Author

Zhang, Shuxia, primary, Xu, Yingru, additional, Xie, Chan, additional, Ren, Liangliang, additional, Wu, Geyan, additional, Yang, Meisongzhu, additional, Wu, Xingui, additional, Tang, Miaoling, additional, Hu, Yameng, additional, Li, Ziwen, additional, Yu, Ruyuan, additional, Liao, Xinyi, additional, Mo, Shuang, additional, Wu, Jueheng, additional, Li, Mengfeng, additional, Song, Erwei, additional, Qi, Yanfei, additional, Song, Libing, additional, and Li, Jun, additional

Published
2020
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