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Weighted gene coexpression network and experimental analyses identify lncRNA SPRR2C as a regulator of the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis Cell Death Dis. (IF 6.304) Pub Date : 2021-01-15 Meijunzi Luo; Pan Huang; Yi Pan; Zhu Zhu; Rong Zhou; Zhibo Yang; Chang Wang
Psoriasis is a chronic inflammatory disease of the skin with highly complex pathogenesis. In this study, we identified lncRNA SPRR2C (small proline-rich protein 2C) as a hub gene with a critical effect on the pathogenesis of psoriasis and response to treatment using both weighted gene coexpression network analysis (WGCNA) and differential expression analysis. SPRR2C expression was significantly upregulated
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PU.1 drives specification of pluripotent stem cell-derived endothelial cells to LSEC-like cells Cell Death Dis. (IF 6.304) Pub Date : 2021-01-14 Jonathan De Smedt; Elise Anne van Os; Irene Talon; Sreya Ghosh; Burak Toprakhisar; Rodrigo Furtado Madeiro Da Costa; Samantha Zaunz; Marta Aguirre Vazquez; Ruben Boon; Pieter Baatsen; Ayla Smout; Stefaan Verhulst; Leo A. van Grunsven; Catherine M. Verfaillie
To date, there is no representative in vitro model for liver sinusoidal endothelial cells (LSECs), as primary LSECs dedifferentiate very fast in culture and no combination of cytokines or growth factors can induce an LSEC fate in (pluripotent stem cell (PSC)-derived) endothelial cells (ECs). Furthermore, the transcriptional programmes driving an LSEC fate have not yet been described. Here, we first
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Adaptive resistance to PI3Kα-selective inhibitor CYH33 is mediated by genomic and transcriptomic alterations in ESCC cells Cell Death Dis. (IF 6.304) Pub Date : 2021-01-14 Yu-xiang Wang; Xu Zhang; Qing-yang Ma; Lan-dian Hu; Xi Zhang; Yi Wang; Lan Xu; Chun-hao Yang; Cun Tan; Xiang-yin Kong; Jian Ding; Ling-hua Meng
Phosphoinositide-3 kinase alpha-specific inhibitors (PI3Kαi) displayed promising potential for the treatment of esophageal squamous cell carcinoma (ESCC) with frequent activation in PI3K signaling. However, acquired resistance is likely to develop and limit the efficacy of PI3Kαi like other targeted therapies. To identify genomic adaptation to PI3Kαi, we applied whole-genome sequencing and detected
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LncRNA TINCR favors tumorigenesis via STAT3–TINCR–EGFR-feedback loop by recruiting DNMT1 and acting as a competing endogenous RNA in human breast cancer Cell Death Dis. (IF 6.304) Pub Date : 2021-01-14 Qin Wang; Jiena Liu; Zilong You; Yanling Yin; Lei Liu; Yujuan Kang; Siwei Li; Shipeng Ning; Hui Li; Yajie Gong; Shouping Xu; Da Pang
The long noncoding RNA (lncRNA) TINCR has recently been found to be associated with the progression of human malignancies, but the molecular mechanism of TINCR action remains elusive, particularly in breast cancer. The oncogenic role of TINCR was examined in vitro and in vivo in breast cancer. Next, the interaction between TINCR, DNMT1, and miR-503-5p methylation was explored. Moreover, the mechanism
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FV-429 induces autophagy blockage and lysosome-dependent cell death of T-cell malignancies via lysosomal dysregulation Cell Death Dis. (IF 6.304) Pub Date : 2021-01-13 Po Hu; Jubo Wang; Yingjie Qing; Hui Li; Wenzhuo Sun; Xiaoxuan Yu; Hui Hui; Qinglong Guo; Jingyan Xu
It is widely accepted that lysosomes are essential for cell homeostasis, and autophagy plays an important role in tumor development. Here, we found FV-429, a synthetic flavonoid compound, inhibited autophagy flux, promoted autophagosomes accumulation, and inhibited lysosomal degradation in T-cell malignancies. These effects were likely to be achieved by lysosomal dysregulation. The destructive effects
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Overcoming hypoxia-induced resistance of pancreatic and lung tumor cells by disrupting the PERK-NRF2-HIF-axis Cell Death Dis. (IF 6.304) Pub Date : 2021-01-13 Alina Küper; Jennifer Baumann; Kirsten Göpelt; Melanie Baumann; Christopher Sänger; Eric Metzen; Philip Kranz; Ulf Brockmeier
Hypoxia-induced resistance of tumor cells to therapeutic treatment is an unresolved limitation due to poor vascular accessibility and protective cell adaptations provided by a network, including PERK, NRF2, and HIF signaling. All three pathways have been shown to influence each other, but a detailed picture remains elusive. To explore this crosstalk in the context of tumor therapy, we generated human
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Intranasal administration of α-synuclein preformed fibrils triggers microglial iron deposition in the substantia nigra of Macaca fascicularis Cell Death Dis. (IF 6.304) Pub Date : 2021-01-13 Jian-Jun Guo; Feng Yue; Dong-Yan Song; Luc Bousset; Xin Liang; Jing Tang; Lin Yuan; Wen Li; Ronald Melki; Yong Tang; Piu Chan; Chuang Guo; Jia-Yi Li
Iron deposition is present in main lesion areas in the brains of patients with Parkinson’s disease (PD) and an abnormal iron content may be associated with dopaminergic neuronal cytotoxicity and degeneration in the substantia nigra of the midbrain. However, the cause of iron deposition and its role in the pathological process of PD are unclear. In the present study, we investigated the effects of the
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SRPS associated protein WDR60 regulates the multipolar-to-bipolar transition of migrating neurons during cortical development Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Cui Li; Yu Zheng; Yufang Zheng; Zhiheng Xu
Mutations of WD40 repeat domain 60 (WDR60) have been identified in short-rib polydactyly syndromes (SRPS I–V), a group of lethal congenital disorders characterized by short ribs, polydactyly, and a range of extraskeletal phenotypes. However, the underlying mechanism is still unclear. Here, we report that WDR60 is essential for embryonic development and plays a critical role in the multipolar-bipolar
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SIRT6 promotes angiogenesis and hemorrhage of carotid plaque via regulating HIF-1α and reactive oxygen species Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Zhou Yang; Yijun Huang; Lei Zhu; Kai Yang; Kun Liang; Jinyun Tan; Bo Yu
As a member of Sirtuins family, SIRT6 participates in the physiological and pathological progress of DNA repair, anti-aging, metabolism, and so on. Several studies have demonstrated that knockdown of SIRT6 inhibited the development of atherosclerosis (AS), indicated SIRT6 as a protective factor for AS. However, we confirmed SIRT6 was significantly overexpressed in human unstable carotid plaques compared
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The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Chengcheng He; Aimin Li; Qiuhua Lai; Jian Ding; Qun Yan; Side Liu; Qingyuan Li
DDX39B is a member of the DEAD box (DDX) RNA helicase family required for nearly all cellular RNA metabolic processes. The exact role and potential molecular mechanism of DDX39B in the progression of human colorectal cancer (CRC) remain to be investigated. In the present study, we demonstrate that DDX39B expression is higher in CRC tissues than in adjacent normal tissues. Gain- and loss-of-function
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DHA/AA alleviates LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3 to inhibit inflammasome complexes assembly Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Guoqiang Fan; Yanfei Li; Jinglong Chen; Yibo Zong; Xiaojing Yang
Pyroptosis is a novel type of programmed cell death associated with the pathogenesis of many inflammatory diseases. Docosahexaenoic acid (DHA) and Arachidonic acid (AA) is widely involved in inflammatory pathological processes. However, the effect and mechanism of DHA and AA on pyroptosis in Kupffer cells are poorly understood. The present study demonstrated that DHA and AA ameliorated lipopolysaccharide
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Structure, function, and pathology of protein O- glucosyltransferases Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Muhammad Zubair Mehboob; Minglin Lang
Protein O-glucosylation is a crucial form of O-glycosylation, which involves glucose (Glc) addition to a serine residue within a consensus sequence of epidermal growth factor epidermal growth factor (EGF)-like repeats found in several proteins, including Notch. Glc provides stability to EGF-like repeats, is required for S2 cleavage of Notch, and serves to regulate the trafficking of Notch, crumbs2
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The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Zhuo Xie; Ying Wang; Guang Yang; Jing Han; Liguo Zhu; Li Li; Shenghong Zhang
Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder that primarily comprises Crohn’s disease (CD) and ulcerative colitis (UC). Owing to its increasing prevalence in Eastern countries and the intractable challenges faced during IBD treatment, extensive research on IBD has been carried out over the last few years. Although the precise aetiology of IBD is undefined, the currently
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Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Ao Chen; Zhangwei Chen; You Zhou; Yuan Wu; Yan Xia; Danbo Lu; Mengkang Fan; Su Li; Jinxiang Chen; Aijun Sun; Yunzeng Zou; Juying Qian; Junbo Ge
Coronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI), bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified. Here, we examine whether the NLRP3 inflammasome contributes to CME-induced cardiac injury
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Period1 mediates rhythmic metabolism of toxins by interacting with CYP2E1 Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Wenhao Ge; Tao Wang; Yang Zhao; Yunxia Yang; Qi Sun; Xiao Yang; Yan Gao; Xi Xu; Jianfa Zhang
The biological clock is an endogenous biological timing system, which controls metabolic functions in almost all organs. Nutrient metabolism, substrate processing, and detoxification are circadian controlled in livers. However, how the clock genes respond to toxins and influence toxicity keeps unclear. We identified the clock gene Per1 was specifically elevated in mice exposed to toxins such as carbon
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Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Min Lu; Xinglei Qin; Yajun Zhou; Gang Li; Zhaoyang Liu; Xiwen Geng; Haodi Yue
Gemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665
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Matrix metalloproteinase-10 protects against acute kidney injury by augmenting epidermal growth factor receptor signaling Cell Death Dis. (IF 6.304) Pub Date : 2021-01-12 Chengxiao Hu; Yangyang Zuo; Qian Ren; Xiaoli Sun; Shan Zhou; Jinlin Liao; Xue Hong; Jinhua Miao; Lili Zhou; Youhua Liu
Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase involved in regulating a wide range of biologic processes, such as apoptosis, cell proliferation, and tissue remodeling. However, the role of MMP-10 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we show that MMP-10 was upregulated in the kidneys and predominantly localized in the tubular epithelium
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The HIV protease inhibitor Saquinavir attenuates sepsis-induced acute lung injury and promotes M2 macrophage polarization via targeting matrix metalloproteinase-9 Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Yao Tong; Zhuang Yu; Zhixia Chen; Renlingzi Zhang; Xibing Ding; Xiaohu Yang; Xiaoyin Niu; Mengzhu Li; Lingling Zhang; Timothy R. Billiar; Bruce R. Pitt; Quan Li
Imbalance of macrophage polarization plays an indispensable role in acute lung injury (ALI), which is considered as a promising target. Matrix metalloproteinase-9 (MMP-9) is expressed in the macrophage, and has a pivotal role in secreting inflammatory cytokines. We reported that saquinavir (SQV), a first-generation human immunodeficiency virus-protease inhibitor, restricted exaggerated inflammatory
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Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Emilie Jaune; Elisa Cavazza; Cyril Ronco; Oleksandr Grytsai; Patricia Abbe; Nedra Tekaya; Marwa Zerhouni; Guillaume Beranger; Lisa Kaminski; Frédéric Bost; Maeva Gesson; Meri Tulic; Paul Hofman; Robert Ballotti; Thierry Passeron; Thomas Botton; Rachid Benhida; Stéphane Rocchi
In the search of biguanide-derived molecules against melanoma, we have discovered and developed a series of bioactive products and identified the promising new compound CRO15. This molecule exerted anti-melanoma effects on cells lines and cells isolated from patients including the ones derived from tumors resistant to BRAF inhibitors. Moreover, CRO15 was able to decrease viability of cells lines from
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ACPA decreases non-small cell lung cancer line growth through Akt/PI3K and JNK pathways in vitro Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Özge Boyacıoğlu; Elif Bilgiç; Cem Varan; Erem Bilensoy; Emirhan Nemutlu; Duygu Sevim; Çetin Kocaefe; Petek Korkusuz
Therapeutic agents used for non-small cell lung cancer (NSCLC) have limited curative efficacy and may trigger serious adverse effects. Cannabinoid ligands exert antiproliferative effect and induce apoptosis on numerous epithelial cancers. We confirmed that CB1 receptor (CB1R) is expressed in NSCLC cells in this study. Arachidonoylcyclopropylamide (ACPA) as a synthetic, CB1R-specific ligand decreased
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Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Zhihao Xu; Ying Zhou; Muziying Liu; Huan Ma; Liangqi Sun; Ayesha Zahid; Yulei Chen; Rongbin Zhou; Minjie Cao; Dabao Wu; Weidong Zhao; Bofeng Li; Tengchuan Jin
Cytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD–CARD interaction between purified NLRP1CARD and ASCCARD experimentally and the filamentous supramolecular
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BUB1B promotes extrahepatic cholangiocarcinoma progression via JNK/c-Jun pathways Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Chen Yu Jiao; Qin Chao Feng; Chang Xian Li; Dong Wang; Sheng Han; Yao Dong Zhang; Wang Jie Jiang; Jiang Chang; Xuehao Wang; Xiang Cheng Li
Currently, the controversy regarding the expression profile and function of BUB1B in different malignancies still exist. In this project, we aimed to explore the role and molecular mechanism of BUB1B in the progression of extrahepatic cholangiocarcinoma (ECC). The expression levels of BUB1B in human ECC were evaluated by immunohistochemistry, western blot, and real-time PCR. The role and mechanism
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Suppressing BCL-XL increased the high dose androgens therapeutic effect to better induce the Enzalutamide-resistant prostate cancer autophagic cell death Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Zhendong Xiang; Yin Sun; Bosen You; Meng Zhang; Chiping Huang; Junfeng Yu; Xiangyun You; Denglong Wu; Chawnshang Chang
Most patients with advanced prostate cancer (PCa) initially respond well to androgen deprivation therapy (ADT) with antiandrogens, but most of them eventually become resistant to ADT. Here, we found that the antiandrogen Enzalutamide-resistant (EnzR) PCa cells can be suppressed by hyper-physiological doses of the androgen DHT. Mechanism dissection indicates that while androgens/androgen receptor (AR)
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Mtu1 defects are correlated with reduced osteogenic differentiation Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Qiufen He; Qiong Zhao; Qianqian Li; Ruolang Pan; Xiongfeng Li; Ye Chen
Accumulating evidence has revealed that mitochondria dynamics and function regulation is essential for the successful mesenchymal stem cell (MSC) differentiation. In the present study, the researchers reported for the first time that Mtu1 defects are correlated with reduced osteogenic differentiation. Using in vitro cultured bone marrow MSCs and stromal cell line MS5, we demonstrated that depressed
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SP1-induced long non-coding RNA SNHG6 facilitates the carcinogenesis of chondrosarcoma through inhibiting KLF6 by recruiting EZH2 Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Fei-Fei Pu; De-Yao Shi; Ting Chen; Yu-Xuan Liu; Bin-Long Zhong; Zhi-Cai Zhang; Wei-Jian Liu; Qiang Wu; Bai-Chuan Wang; Zeng-Wu Shao; Tong-Chuan He; Jian-Xiang Liu
Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma
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Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Yao Wang; Qian Chen; Fangzhou Jiao; Chunxia Shi; Maohua Pei; Luwen Wang; Zuojiong Gong
Pyroptosis is a new necrosis pattern of hepatocyte during liver inflammation in acute liver failure (ALF). Histone deacetylase 2 (HDAC2) is associated with several pathological conditions in the liver system. The aim of this study is to investigate whether knockdown or pharmacological inhibition of HDAC2 could reduce the level of pyroptosis in ALF through ULK1-NLRP3-pyroptosis pathway. The role of
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The redox language in neurodegenerative diseases: oxidative post-translational modifications by hydrogen peroxide Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Yew Mun Lee; Weifeng He; Yih-Cherng Liou
Neurodegenerative diseases, a subset of age-driven diseases, have been known to exhibit increased oxidative stress. The resultant increase in reactive oxygen species (ROS) has long been viewed as a detrimental byproduct of many cellular processes. Despite this, therapeutic approaches using antioxidants were deemed unsuccessful in circumventing neurodegenerative diseases. In recent times, it is widely
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Legumain promotes tubular ferroptosis by facilitating chaperone-mediated autophagy of GPX4 in AKI Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Chuan’ai Chen; Dekun Wang; Yangyang Yu; Tianyuan Zhao; Ningning Min; Yan Wu; Lichun Kang; Yong Zhao; Lingfang Du; Mianzhi Zhang; Junbo Gong; Zhujun Zhang; Yuying Zhang; Xue Mi; Shijing Yue; Xiaoyue Tan
Legumain is required for maintenance of normal kidney homeostasis. However, its role in acute kidney injury (AKI) is still unclear. Here, we induced AKI by bilateral ischemia-reperfusion injury (IRI) of renal arteries or folic acid in lgmnWT and lgmnKO mice. We assessed serum creatinine, blood urea nitrogen, histological indexes of tubular injury, and expression of KIM-1 and NGAL. Inflammatory infiltration
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ALKBH5 suppresses tumor progression via an m 6 A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Ye Yuan; Gege Yan; Mingyu He; Hong Lei; Linqiang Li; Yang Wang; Xiaoqi He; Guanghui Li; Quan Wang; Yuelin Gao; Zhezhe Qu; Zhongting Mei; Zhihua Shen; Jiaying Pu; Ao Wang; Wei Zhao; Huiwei Jiang; Weijie Du; Lei Yang
ALKBH5 is the main enzyme for m6A-based demethylation of RNAs and it has been implicated in many biological and pathophysiological processes. Here, we aimed to explore the potential involvement of ALKBH5 in osteosarcoma and decipher the underlying cellular/molecular mechanisms. We discovered downregulated levels of demethylase ALKBH5 were correlated with increased m6A methylation in osteosarcoma cells/tissues
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Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Jung-Hwan Baek; Da-Hyun Kim; Jaegyeong Lee; Seok-Jun Kim; Kyung-Hee Chun
Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA expression of galectin-1 was detected in white adipose tissues (WATs) of mice that were fed a high-fat diet (HFD)
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Necroptosis is active and contributes to intestinal injury in a piglet model with lipopolysaccharide challenge Cell Death Dis. (IF 6.304) Pub Date : 2021-01-11 Yulan Liu; Qiao Xu; Yang Wang; Tianzeng Liang; Xiangen Li; Dan Wang; Xiuying Wang; Huiling Zhu; Kan Xiao
Necroptosis, a newly discovered form of programmed cell death that combines the features of apoptosis and necrosis, is important in various physiological and pathological disorders. However, the role of necroptosis on intestinal injury during sepsis has been rarely evaluated. This study aimed to investigate the presence of necroptosis in intestinal injury, and its contribution to intestinal injury
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GNA13 regulates BCL2 expression and the sensitivity of GCB-DLBCL cells to BCL2 inhibitors in a palmitoylation-dependent manner Cell Death Dis. (IF 6.304) Pub Date : 2021-01-09 Zhizhou Xia; Xiuli Zhang; Ping Liu; Ruihong Zhang; Zhangsen Huang; Donghe Li; Xinhua Xiao; Min Wu; Nannan Ning; Qianqian Zhang; Jianmin Zhang; Mingzhu Liu; Bo Jiao; Ruibao Ren
GNA13, encoding one of the G protein alpha subunits of heterotrimeric G proteins that transduce signals of G protein-coupled receptors (GPCR), is frequently mutated in germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) with poor prognostic outcomes. Due to the “undruggable” nature of GNA13, targeted therapy for these patients is not available. In this study, we found that palmitoylation
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Liver fibrosis-induced muscle atrophy is mediated by elevated levels of circulating TNFα Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Tamaki Kurosawa; Momo Goto; Noriyuki Kaji; Satoshi Aikiyo; Taiki Mihara; Madoka Ikemoto-Uezumi; Masashi Toyoda; Nobuo Kanazawa; Tatsu Nakazawa; Masatoshi Hori; Akiyoshi Uezumi
Liver cirrhosis is a critical health problem associated with several complications, including skeletal muscle atrophy, which adversely affects the clinical outcome of patients independent of their liver functions. However, the precise mechanism underlying liver cirrhosis-induced muscle atrophy has not been elucidated. Here we show that serum factor induced by liver fibrosis leads to skeletal muscle
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Neutral lipids as early biomarkers of cellular fate: the case of α-synuclein overexpression Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Natalia P. Alza; Melisa A. Conde; Paola G. Scodelaro-Bilbao; Gabriela A. Salvador
α-synuclein (α-syn) accumulation and aggregation is a common pathological factor found in synucleinopathies, a group of neurodegenerative disorders that includes Parkinson´s disease (PD). It has been proposed that lipid dyshomeostasis is responsible for the occurrence of PD-related processes, however, the precise role of lipids in the onset and progression of neurodegenerative disorders remains unclear
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Prostate apoptosis response-4 and tumor suppression: it’s not just about apoptosis anymore Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Anees Rahman Cheratta; Faisal Thayyullathil; Siraj Pallichankandy; Karthikeyan Subburayan; Ameer Alakkal; Sehamuddin Galadari
The tumor suppressor prostate apoptosis response-4 (Par-4) has recently turned ‘twenty-five’. Beyond its indisputable role as an apoptosis inducer, an increasing and sometimes bewildering, new roles for Par-4 are being reported. These roles include its ability to regulate autophagy, senescence, and metastasis. This growing range of responses to Par-4 is reflected by our increasing understanding of
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TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Yan Zhou; Tao Tao; Guangjie Liu; Xuan Gao; Yongyue Gao; Zong Zhuang; Yue Lu; Han Wang; Wei Li; Lingyun Wu; Dingding Zhang; Chunhua Hang
Neuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was
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Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Faisal Thayyullathil; Anees Rahman Cheratta; Ameer Alakkal; Karthikeyan Subburayan; Siraj Pallichankandy; Yusuf A. Hannun; Sehamuddin Galadari
Ferroptosis is a type of regulated cell death characterized by ROS accumulation and devastating lipid peroxidation (LPO). The role of acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, in the induction of apoptosis has been studied; however, to date its role in ferroptosis is unclear. In this study, we report that ASM plays a hitherto unanticipated role in promoting ferroptosis.
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CXCR4 uses STAT3-mediated slug expression to maintain radioresistance of non-small cell lung cancer cells: emerges as a potential prognostic biomarker for lung cancer Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Jeong-Yub Kim; Hee-Jin Kim; Chan-Woong Jung; Tae Sup Lee; Eun Ho Kim; Myung-Jin Park
Lung cancer is one of the most common reasons for cancer-induced mortality across the globe, despite major advancements in the treatment strategies including radiotherapy and chemotherapy. Existing reports suggest that CXCR4 is frequently expressed by malignant tumor and is imperative for vascularization, tumor growth, cell migration, and metastasis pertaining to poor prognosis. In this study, we infer
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Interleukin-38 ameliorates poly(I:C) induced lung inflammation: therapeutic implications in respiratory viral infections Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Xun Gao; Paul Kay Sheung Chan; Grace Chung Yan Lui; David Shu Cheong Hui; Ida Miu-Ting Chu; Xiaoyu Sun; Miranda Sin-Man Tsang; Ben Chung Lap Chan; Christopher Wai-Kei Lam; Chun-Kwok Wong
Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with
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Roles of HDAC3-orchestrated circadian clock gene oscillations in diabetic rats following myocardial ischaemia/reperfusion injury Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Zhen Qiu; Hao Ming; Shaoqing Lei; Bin Zhou; Bo Zhao; Yanli Yu; Rui Xue; Zhongyuan Xia
The circadian clock is closely related to the development of diabetes mellitus and cardiovascular disease, and disruption of the circadian clock exacerbates myocardial ischaemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop that controls the expression pattern of the circadian nuclear receptor Rev-erbα to maintain the stability of circadian genes such
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Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4 + Treg cells in ovarian cancer cells microenvironment Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Rui Xu; Ming Wu; Shuna Liu; Wenwen Shang; Rong Li; Juan Xu; Lei Huang; Fang Wang
Immunotherapy is expected to become the most promising new treatment for ovarian cancer owing to its immunogenicity. However, immunosuppression in the tumor microenvironment is a major obstacle to the efficacy of tumor therapy. Studies have found different metabolism ways of regulatory T cells (Tregs) in the cancer environment may be related to the immunosuppression and Toll-like receptor 8 (TLR8)
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Combined and selective miR-21 silencing and doxorubicin delivery in cancer cells using tailored DNA nanostructures Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Sofia Raniolo; Valeria Unida; Giulia Vindigni; Carmine Stolfi; Federico Iacovelli; Alessandro Desideri; Silvia Biocca
MicroRNAs play an important role in tumorigenesis and, among them, miR-21 is found to be aberrantly up-regulated in various tumors. The tumor-associated antigen, folate receptor alpha is a GPI-membrane protein overexpressed in many malignant tumors of epithelial origin, including ovarian and cervical cancers. Covalently bound octahedral DNA nanocages were functionalized with folate molecules and utilized
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TRIB2 modulates proteasome function to reduce ubiquitin stability and protect liver cancer cells against oxidative stress Cell Death Dis. (IF 6.304) Pub Date : 2021-01-07 Susu Guo; Yuxin Chen; Yueyue Yang; Xiao Zhang; Lifang Ma; Xiangfei Xue; Yongxia Qiao; Jiayi Wang
The regulation of homeostasis in the Ubiquitin (Ub) proteasome system (UPS) is likely to be important for the development of liver cancer. Tribbles homolog 2 (TRIB2) is known to affect Ub E3 ligases (E3s) in liver cancer. However, whether TRIB2 regulates the UPS in other ways and the relevant mechanisms are still unknown. Here, we reveal that TRIB2 decreased Ub levels largely by stimulating proteasome
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LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells Cell Death Dis. (IF 6.304) Pub Date : 2021-01-06 Minmin Xiong; Mengshi Wu; Dan Peng; Weijun Huang; Zehong Chen; Haoxian Ke; Zewen Chen; Wu Song; Yonghua Zhao; Andy P. Xiang; Xiaomin Zhong
Long non-coding RNA (lncRNA) DANCR has been reported to participate in key processes such as stem cell differentiation and tumorigenesis. In a high throughput screening for lncRNAs involved in Doxorubicin-induced apoptosis, we found DANCR was suppressed by Doxorubicin and it acted as an important repressor of apoptosis in colorectal cancer. Further studies demonstrated that DANCR promoted the oncogenic
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Gefitinib initiates sterile inflammation by promoting IL-1β and HMGB1 release via two distinct mechanisms Cell Death Dis. (IF 6.304) Pub Date : 2021-01-06 Takuya Noguchi; Yuto Sekiguchi; Yuki Kudoh; Rio Naganuma; Tomohiro Kagi; Akiko Nishidate; Kazuhiro Maeda; Chizuru Ishii; Takashi Toyama; Yusuke Hirata; Gi-Wook Hwang; Atsushi Matsuzawa
Anticancer drug gefitinib causes inflammation-based side effects, such as interstitial pneumonitis. However, its mechanisms remain unknown. Here, we provide evidence that gefitinib elicits pro-inflammatory responses by promoting mature-interleukin-1β (IL-1β) and high-mobility group box 1 (HMGB1) release. Mitochondrial reactive oxygen species (mtROS) driven by gefitinib stimulated the formation of the
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KDM6B is an androgen regulated gene and plays oncogenic roles by demethylating H3K27me3 at cyclin D1 promoter in prostate cancer Cell Death Dis. (IF 6.304) Pub Date : 2021-01-06 Zhi Cao; Xiaolei Shi; Feng Tian; Yu Fang; Jason Boyang Wu; Stefan Mrdenovic; Xinwen Nian; Jin Ji; Huan Xu; Chen Kong; Yalong Xu; Xi Chen; Yuhua Huang; Xuedong Wei; Yongwei Yu; Bo Yang; Leland W. K. Chung; Fubo Wang
Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, plays oncogenic or antitumoral roles in malignant tumors depending on the type of tumor cell. However, how this histone modifier affects the progression of prostate cancer (PCa) is still unknown. Here we analyzed sequenced gene expression data and tissue microarray to explore the expression features and prognostic
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TRIM21-regulated Annexin A2 plasma membrane trafficking facilitates osteosarcoma cell differentiation through the TFEB-mediated autophagy Cell Death Dis. (IF 6.304) Pub Date : 2021-01-06 Huan-Tian Zhang; Qingzhong Zeng; Baomeng Wu; Junlei Lu; Kui-Leung Tong; Jiebin Lin; Qiu-Yu Liu; Lipei Xu; Jie Yang; Xiaohui Liu; Wanting Liu; Yun-Fang Zhang; Qionghua Lian; Langxia Liu; Xuejuan Gao
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, which is characterized by dysfunctional autophagy and poor differentiation. Our recent studies have suggested that the tripartite motif containing-21 (TRIM21) plays a crucial role in regulating OS cell senescence and proliferation via interactions with several proteins. Yet, its implication in autophagy and
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Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response Cell Death Dis. (IF 6.304) Pub Date : 2021-01-06 Ai-Ling Tian; Qi Wu; Peng Liu; Liwei Zhao; Isabelle Martins; Oliver Kepp; Marion Leduc; Guido Kroemer
The integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger
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Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke Cell Death Dis. (IF 6.304) Pub Date : 2021-01-06 Jin Yang; Lu-Lu Cao; Xi-Peng Wang; Wei Guo; Ruo-Bing Guo; Yu-Qin Sun; Teng-Fei Xue; Zhen-Yu Cai; Juan Ji; Hong Cheng; Xiu-Lan Sun
Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis
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A new risk factor indicator for papillary thyroid cancer based on immune infiltration Cell Death Dis. (IF 6.304) Pub Date : 2021-01-06 Zhou Yang; Xiyi Wei; Yitong Pan; Jingyuan Xu; Yan Si; Zhijun Min; Bo Yu
Increasing evidence has indicated a close association between immune infiltration in cancer and clinical outcomes. However, related research in thyroid cancer is still deficient. Our research comprehensively investigated the immune infiltration of thyroid cancer. Data derived from TCGA and GEO databases were analyzed by the CIBERSORT, ESTIMATE, and EPIC algorithms. The CIBERSORT algorithm calculates
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HOXA5 counteracts the function of pathological scar-derived fibroblasts by partially activating p53 signaling Cell Death Dis. (IF 6.304) Pub Date : 2021-01-05 Yimin Liang; Renpeng Zhou; Xiujun Fu; Chen Wang; Danru Wang
The inactivation of p53 can lead to the formation of pathological scars, including hypertrophic scars and keloids. HOXA5 has been reported to be a critical transcription factor in the p53 pathway in cancers. However, whether HOXA5 also plays a role in pathological scar progression through activating p53 signaling remains unknown. In this study, we first demonstrated that HOXA5 overexpression in hypertrophic
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Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer Cell Death Dis. (IF 6.304) Pub Date : 2021-01-05 Zhi Long; Liang Deng; Chao Li; Qiangrong He; Yao He; Xiheng Hu; Yi Cai; Yu Gan
The rising of a highly aggressive subtype of castration-resistant prostate cancer (CRPC) named treatment-induced neuroendocrine prostate cancer (t-NEPC) after androgen deprivation therapy (ADT) is well known for its features of the neuroendocrine differentiation (NED) and androgen receptor (AR) independence. However, t-NEPC is still largely unknown. Here, we found that EHF is notably depressed in t-NEPC
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SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype Cell Death Dis. (IF 6.304) Pub Date : 2021-01-05 Dario Bongiovanni; Melissa Klug; Olga Lazareva; Simon Weidlich; Marina Biasi; Simona Ursu; Sarah Warth; Christian Buske; Marina Lukas; Christoph D. Spinner; Moritz von Scheidt; Gianluigi Condorelli; Jan Baumbach; Karl-Ludwig Laugwitz; Markus List; Isabell Bernlochner
Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with
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BTF3 confers oncogenic activity in prostate cancer through transcriptional upregulation of Replication Factor C Cell Death Dis. (IF 6.304) Pub Date : 2021-01-05 Yuan Zhang; Xiang Gao; Jingyan Yi; Xiaolin Sang; Zhihong Dai; Zhiwei Tao; Min Wang; Lanlin Shen; Yaxun Jia; Daqing Xie; Hailing Cheng; Zhiyu Liu; Pixu Liu
High levels of Basic Transcription Factor 3 (BTF3) have been associated with prostate cancer. However, the mechanisms underlying the role of BTF3 as an oncogenic transcription factor in prostate tumorigenesis have not been explored. Herein, we report that BTF3 confers oncogenic activity in prostate cancer cells. Mechanistically, while both BTF3 splicing isoforms (BTF3a and BTF3b) promote cell growth
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Nrf2 overexpression increases risk of high tumor mutation burden in acute myeloid leukemia by inhibiting MSH2 Cell Death Dis. (IF 6.304) Pub Date : 2021-01-05 Ping Liu; Dan Ma; Ping Wang; Chengyun Pan; Qin Fang; Jishi Wang
Nuclear factor erythroid 2-related factor 2 (Nrf2, also called NFE2L2) plays an important role in cancer chemoresistance. However, little is known about the role of Nrf2 in tumor mutation burden and the effect of Nrf2 in modulating DNA mismatch repair (MMR) gene in acute myeloid leukemia (AML). Here we show that Nrf2 expression is associated with tumor mutation burden in AML. Patients with Nrf2 overexpression
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MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway Cell Death Dis. (IF 6.304) Pub Date : 2021-01-05 Shuhua Zhao; Lu Cheng; Yuan Shi; Jia Li; Qinghui Yun; Hong Yang
MIEF2 (mitochondrial elongation factor 2) is one of the key regulators of mitochondrial fission. Bioinformatics analysis indicated that high expression of MIEF2 predicted a poor prognosis in ovarian cancer patients. However, the relationship between MIEF2 and aberrant lipid metabolism in OC remains elusive. In this study, we demonstrated that MIEF2 significantly promoted lipid synthesis, while has
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Snai1-induced partial epithelial–mesenchymal transition orchestrates p53–p21-mediated G2/M arrest in the progression of renal fibrosis via NF-κB-mediated inflammation Cell Death Dis. (IF 6.304) Pub Date : 2021-01-05 Ruochen Qi; Jiyan Wang; Yamei Jiang; Yue Qiu; Ming Xu; Ruiming Rong; Tongyu Zhu
Renal fibrosis is the common feature of all progressive kidney diseases and exerts great burden on public health worldwide. The maladaptive repair mechanism of tubular epithelial cells, an important mediator of renal fibrogenesis, manifests with partial epithelial–mesenchymal transition (EMT) and cell cycle arrest. The aim of this study is to investigate the possible correlation between partial EMT
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MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1 Cell Death Dis. (IF 6.304) Pub Date : 2021-01-04 Zeyan Li; Shuo Zhao; Shiqin Zhu; Yidong Fan
MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue using bioinformatics algorithms. MiR-153-5p was identified as a candidate miRNA to promote