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Cell Death & Disease

Linpeng Li, Keshi Chen, Yi Wu, Qi Long, Danyun Zhao, Bochao Ma, Duanqing Pei, Xingguo Liu
MicroRNAs (miRNAs) play crucial roles in the establishment of pluripotent state by controlling pluripotent network. However, the molecular mechanisms controlling miRNAs during somatic cell reprogramming remain obscure. In this study, we show Gadd45a (growth arrest and DNA-damage-inducible protein 45a) enhances reprogramming by activating miR-295. Furthermore, we show that Gadd45a binds the promoter regions of miR-295. Nuclease accessibility assay indicates that Gadd45a opens the promoter regions of miR-295...
October 12, 2017: Cell Death & Disease
Yu-Han Meng, Wen-Jie Zhou, Li-Ping Jin, Li-Bing Liu, Kai-Kai Chang, Jie Mei, Hui Li, Jian Wang, Da-Jin Li, Ming-Qing Li
Decidual macrophages (dMϕ) contribute to maternal-fetal tolerance. However, the mechanism of dMϕ differentiation during pregnancy is still largely unknown. Here, we report that receptor activator for nuclear factor-κ B ligand (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal cells (DSCs), polarizes dMϕ toward a M2 phenotype. This polarization is mediated through activation of Akt/signal transducer and activator of transcription 6 (STAT6) signaling, which is associated with the upregulation of histone H3 lysine-27 demethylase Jmjd3 and IRF4 in dMϕ...
October 12, 2017: Cell Death & Disease
Yuewen Tang, Pei Yu, Lin Cheng
Neural stem cells (NSCs) have a unique role in neural regeneration. Cell therapy based on NSC transplantation is a promising tool for the treatment of nervous system diseases. However, there are still many issues and controversies associated with the derivation and therapeutic application of these cells. In this review, we summarize the different sources of NSCs and their derivation methods, including direct isolation from primary tissues, differentiation from pluripotent stem cells and transdifferentiation from somatic cells...
October 12, 2017: Cell Death & Disease
Yetao Xu, Zhiping Ge, Erbao Zhang, Qing Zuo, Shiyun Huang, Nana Yang, Dan Wu, Yuanyuan Zhang, Yanzi Chen, Haoqin Xu, Huan Huang, Zhiyan Jiang, Lizhou Sun
Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE...
October 12, 2017: Cell Death & Disease
Xi Sun, Bo Li, Bingqian Xie, Zhijian Xu, Gaomei Chang, Yi Tao, Yong Zhang, Shuaikang Chang, Yingcong Wang, Dandan Yu, Yongsheng Xie, Tingye Li, Houcai Wang, Gege Chen, Liangning Hu, Jun Hou, Yiwen Zhang, Wenqin Xiao, Lu Gao, Jumei Shi, Weiliang Zhu
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, characterized by a rapidly increasing painless mass. A novel compound, DCZ3301, was synthesized that exerted direct cytotoxicity against DLBCL cell lines. The effects of DCZ3301 on DLBCL cells in vitro and in vivo and the associated mechanisms were investigated. DCZ3301 inhibited the viability of DLBCL cell lines, even in the presence of protumorigenesis cytokines. Additionally, the compound induced apoptosis and cell cycle arrest at the G2/M phase by reducing mitochondrial membrane potential...
October 12, 2017: Cell Death & Disease
Shibao Li, Zhiyuan Wu, Ping Ma, Yinhai Xu, Yuming Chen, Hua Wang, Ping He, Zhihua Kang, Lingyu Yin, Yao Zhao, Xinju Zhang, Xiao Xu, Xiaochao Ma, Ming Guan
The downregulation of receptor tyrosine kinase EphA7 is frequent in epithelial cancers and linked to tumor progression. However, the detailed mechanism of EphA7-mediated prostate tumor progression remains elusive. To test the role of EphA7 receptor in prostate cancer (PCa) progression directly, we generated EphA7 receptor variants that were either lacking the cytoplasmic domain or carrying a point mutation that inhibits its phosphorylation by site-directed mutagenesis. Overexpression of wild-type (WT) EphA7 in PCa cells resulted in decreased tumor volume and increased tumor apoptosis in primary tumors...
October 12, 2017: Cell Death & Disease
Xin-Yu Wang, Heng Yang, Min-Ge Wang, Du-Bao Yang, Zhen-Yong Wang, Lin Wang
Autophagy has an important renoprotective function and we recently found that autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we aimed to investigate the protective effect of trehalose (Tre), a novel autophagy activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT) cells. First, data showed that Tre treatment significantly decreased Cd-induced apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic pathway, evidenced by morphological analysis, flow cytometric and immunoblot assays...
October 12, 2017: Cell Death & Disease
Matthew Merski, Cátia Moreira, Rui Mv Abreu, Maria João Ramos, Pedro A Fernandes, L Miguel Martins, Pedro José Barbosa Pereira, Sandra Macedo-Ribeiro
HtrA2 (high-temperature requirement 2) is a human mitochondrial protease that has a role in apoptosis and Parkinson's disease. The structure of HtrA2 with an intact catalytic triad was determined, revealing a conformational change in the active site loops, involving mainly the regulatory LD loop, which resulted in burial of the catalytic serine relative to the previously reported structure of the proteolytically inactive mutant. Mutations in the loops surrounding the active site that significantly restricted their mobility, reduced proteolytic activity both in vitro and in cells, suggesting that regulation of HtrA2 activity cannot be explained by a simple transition to an activated conformational state with enhanced active site accessibility...
October 12, 2017: Cell Death & Disease
Kuijie Liu, Weidong Chen, Sanlin Lei, Li Xiong, Hua Zhao, Dong Liang, Zhendong Lei, Nanjiang Zhou, Hongliang Yao, Ying Liang
Colorectal cancer (CRC) is a most common digestive system malignant tumor. p53 mutation has essential role in cancers and is frequently observed in CRC and presents a huge challenge. p53 mutation has been reported to attenuate the inhibitory effect of photofrin-based photodynamic therapy (PDT). p53 mutation-induced gain of function brings up the dysfunction of carcinogenic factors, including miRNAs. Our research found that PDT suppressed CRC cell viability, reduced the tumor size and prolonged the survival time, all of which could be attenuated by p53 mutation or deletion...
October 12, 2017: Cell Death & Disease
Hongping Xia, Kam M Hui
No abstract text is available yet for this article.
October 12, 2017: Cell Death & Disease
Juan Wang, Huiling Li, Shuangfa Qiu, Zheng Dong, Xudong Xiang, Dongshan Zhang
Despite DNA methylation occurred in acute kidney injury (AKI), how it influenced progression of AKI remains unclear. Methyl-CpG-binding domain protein 2 (MBD2), a protein readers of methylation, was used to analyze the impact of DNA methylation on vancomycin (VAN)-induced AKI. Here, in cultured human kidney tubular epithelial cells (HK-2), we show that knockdown of MBD2 by siRNA attenuated VAN-induced apoptosis, caspase activity, and the expression of BAX and cleaved caspase 3. Interestingly, knockdown of MBD2 by siRNA was associated with the suppression of miR-301a-5p...
October 12, 2017: Cell Death & Disease
Dasheng Lin, Paolo Alberton, Manuel Delgado Caceres, Elias Volkmer, Matthias Schieker, Denitsa Docheva
Tenomodulin (Tnmd) is the best-known mature marker for tendon and ligament lineage cells. It is important for tendon maturation, running performance and has key implications for the resident tendon stem/progenitor cells (TSPCs). However, its exact functions during the tendon repair process still remain elusive. Here, we established an Achilles tendon injury model in a Tnmd knockout (Tnmd(-/-)) mouse line. Detailed analyses showed not only a very different scar organization with a clearly reduced cell proliferation and expression of certain tendon-related genes, but also increased cell apoptosis, adipocyte and blood vessel accumulation in the early phase of tendon healing compared with their wild-type (WT) littermates...
October 12, 2017: Cell Death & Disease
Joaquim Moreno-Càceres, Daniel Caballero-Díaz, Zeribe Chike Nwosu, Christoph Meyer, Judit López-Luque, Andrea Malfettone, Raquel Lastra, Teresa Serrano, Emilio Ramos, Steven Dooley, Isabel Fabregat
Hepatocellular carcinoma (HCC) is a heterogeneous tumour associated with poor prognostic outcome. Caveolin-1 (CAV1), a membrane protein involved in the formation of caveolae, is frequently overexpressed in HCC. Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine having a dual role in hepatocarcinogenesis: inducer of apoptosis at early phases, but pro-tumourigenic once cells acquire mechanisms to overcome its suppressor effects. Apoptosis induced by TGF-β is mediated by upregulation of the NADPH oxidase NOX4, but counteracted by transactivation of the epidermal growth factor receptor (EGFR) pathway...
October 12, 2017: Cell Death & Disease
Xiaoliang Xu, Yin Yin, Junwei Tang, Yu Xie, Zhuo Han, Xudong Zhang, Qiaoyu Liu, Xihu Qin, Xinli Huang, Beicheng Sun
Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we confirmed a new long non-coding RNA Myd88 aberrant upregulated in HCC located upstream of Myd88 and verified a positive regulation relationship between them indicating that Lnc-Myd88 might participate in the enhanced expression of Myd88 in HCC...
October 12, 2017: Cell Death & Disease
Quanbo Ji, Xiaojie Xu, Ling Li, Stuart B Goodman, Wenzhi Bi, Meng Xu, Yameng Xu, Zhongyi Fan, William J Maloney, Qinong Ye, Yan Wang
Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated...
October 12, 2017: Cell Death & Disease
Chao Lei, Feng Du, Lina Sun, Ting Li, Tingyu Li, Yali Min, Aiying Nie, Xin Wang, Lei Geng, Yuanyuan Lu, Xiaodi Zhao, Yongquan Shi, Daiming Fan
Metastasis is a major clinical obstacle responsible for the high mortality and poor prognosis of gastric cancer (GC). MicroRNAs (miRNAs) are critical mediators of metastasis that act by modulating their target genes. In this study, we found that miR-143 and miR-145 act via a common target gene, MYO6, to regulate the epithelial-mesenchymal transition (EMT) and inhibit metastasis. We determined that miR-143 and miR-145 were downregulated in GC, and the ectopic expression of miR-143 and/or miR-145 inhibited GC cell migration and metastasis...
October 12, 2017: Cell Death & Disease
Yongtao Xiao, Jun Wang, Weihui Yan, Kejun Zhou, Yi Cao, Wei Cai
The p38α mitogen-activated protein kinase (MAPK) has been related to gluconeogenesis and lipid metabolism. However, the roles and related mechanisms of p38α MAPK in intestinal failure (IF)-associated liver steatosis remained poor understood. Here, our experimental evidence suggested that p38α MAPK significantly suppressed the fat accumulation in livers of IF patients mainly through two mechanisms. On the one hand, p38α MAPK increased hepatic bile acid (BA) synthesis by upregulating the expression of the rate-limiting enzyme cholesterol 7-α-hydroxylase (CYP7A1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which in turn activated the transcription of the CYP7A1...
October 12, 2017: Cell Death & Disease
Junjie Xu, Longbo Zheng, Jiang Chen, Yin Sun, Hui Lin, Ren-An Jin, Minyue Tang, Xiao Liang, Xiujun Cai
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR...
October 12, 2017: Cell Death & Disease
Lujun Zhou, Qiang Zhang, Peng Zhang, Lei Sun, Can Peng, Zengqiang Yuan, Jinbo Cheng
Oxidative stress-induced mitochondrial dysfunction and neuronal cell death have important roles in the development of neurodegenerative diseases. Dynamin related protein 1 (Drp1) is a critical factor in regulating mitochondrial dynamics. A variety of posttranslational modifications of Drp1 have been reported, including phosphorylation, ubiquitination, sumoylation and S-nitrosylation. In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation...
October 12, 2017: Cell Death & Disease
Pradip Devhare, Keith Meyer, Robert Steele, Ratna B Ray, Ranjit Ray
The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs...
October 12, 2017: Cell Death & Disease
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