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Cell Death & Disease

Yi-Pin Lv, Yong-Sheng Teng, Fang-Yuan Mao, Liu-Sheng Peng, Jin-Yu Zhang, Ping Cheng, Yu-Gang Liu, Hui Kong, Ting-Ting Wang, Xiao-Long Wu, Chuan-Jie Hao, Weisan Chen, Shi-Ming Yang, Yong-Liang Zhao, Bin Han, Qiang Ma, Quan-Ming Zou, Yuan Zhuang
Interleukin (IL)-induced inflammatory responses are critical for the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. IL-33 represents a recently discovered proinflammatory cytokine involved in inflammatory diseases, but its relevance to H. pylori-induced gastritis is unknown. Here, we found that gastric IL-33 mRNA and protein expression were elevated in gastric mucosa of both patients and mice infected with H. pylori, which is positively correlated with bacterial load and the degree of gastritis...
April 25, 2018: Cell Death & Disease
Liya Li, Wenjia Liu, Hong Wang, Qianjuan Yang, Liqiang Zhang, Fang Jin, Yan Jin
Histone deacetylases (HDAC) plays important roles in the post-translational modifications of histone cores as well as non-histone targets. Many of them are involved in key inflammatory processes. Despite their importance, whether and how HDAC9 is regulated under inflammatory conditions remains unclear. The aim of this study was to evaluate the effects of HDAC9 under chronic inflammation condition in human periodontal ligament stromal cell (PDLSCs) and to explore the underlying regulatory mechanism. PDLSCs from healthy or periodontitis human tissue was compared...
April 24, 2018: Cell Death & Disease
Wondossen Sime, Qiankun Niu, Yasmin Abassi, Katarzyna Chmielarska Masoumi, Reihaneh Zarrizi, Julie Bonne Køhler, Sven Kjellström, Vito Alessandro Lasorsa, Mario Capasso, Haian Fu, Ramin Massoumi
BRCA1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme that is associated with multiprotein complexes that regulate key cellular pathways, including cell cycle, cellular differentiation, cell death, and the DNA damage response. In this study, we found that the reduced expression of BAP1 pro6motes the survival of neuroblastoma cells, and restoring the levels of BAP1 in these cells facilitated a delay in S and G2/M phase of the cell cycle, as well as cell apoptosis. The mechanism that BAP1 induces cell death is mediated via an interaction with 14-3-3 protein...
April 24, 2018: Cell Death & Disease
Yuting Gu, Xinyuan Ding, Jiefang Huang, Mingxing Xue, Jie Zhang, Qiwei Wang, Hongshuang Yu, Yanan Wang, Fang Zhao, Hui Wang, Min Jin, Yeming Wu, Yanyun Zhang
It is known that proinflammatory cytokines empower multipotent mesenchymal stromal cells (MSCs) the immunosuppressive capacity to treat various inflammatory diseases. Nevertheless, how the proinflammatory cytokines modulate the immunosuppressive capacity of MSCs is poorly understood. In the present study, we identified that the deubiquitinating enzyme ubiquitin C-terminal hydrolase 1 (UCHL1) was upregulated in MSCs upon stimulation of proinflammatory cytokines IFN-γ plus TNF-α. Interestingly, through intervening UCHL1 by shRNA knockdown or its inhibitor LDN57444 or overexpression, we found that UCHL1 played a critical role in suppressing cytokines-induced inducible nitric oxide synthase expression in murine MSCs and indoleamine 2,3-dioxygenase expression in human MSCs, thereby restrained their immunosuppressive capacity...
April 23, 2018: Cell Death & Disease
Florian Schubert, Juliane Rapp, Prisca Brauns-Schubert, Lisa Schlicher, Kerstin Stock, Manuela Wissler, Martina Weiß, Céline Charvet, Christoph Borner, Ulrich Maurer
Growth factor withdrawal induces rapid apoptosis via mitochondrial outer membrane permeabilization. We had previously observed that cell death of IL-3-dependent Ba/F3 cells, induced by removal of the growth factor, required the activity of the kinase GSK-3. Employing CRISPR/Cas9-mediated gene knockout, we aimed to identify pro-apoptotic GSK-3 regulated factors in this process. Knockout of either Puma or Bim demonstrated that the induction of Puma, but not Bim, was crucial for apoptosis induced by IL-3 deprivation...
April 23, 2018: Cell Death & Disease
Shuo Liu, Yun Li, Harry M C Choi, Chinmoy Sarkar, Eugene Y Koh, Junfang Wu, Marta M Lipinski
Necroptosis, a regulated necrosis pathway mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3), is induced following spinal cord injury (SCI) and thought to contribute to neuronal and glial cell death. However, mechanisms leading to activation of necroptosis after SCI remain unclear. We have previously shown that autophagy, a catabolic pathway facilitating degradation of cytoplasmic proteins and organelles in a lysosome-dependent manner, is inhibited following SCI in rats. Our current data confirm that inhibition of autophagy also occurs after thoracic contusive SCI in the mouse model, as indicated by accumulation of both the autophagosome marker, LC3-II and autophagy cargo protein, p62/SQSTM1...
April 23, 2018: Cell Death & Disease
Xiangyu Dai, Chao Chen, Qianlei Yang, Junchao Xue, Xiong Chen, Baofei Sun, Fei Luo, Xinlu Liu, Tian Xiao, Hui Xu, Qian Sun, Aihua Zhang, Qizhan Liu
Intercellular communication between malignant cells and neighboring nonmalignant cells is involved in carcinogenesis. In the progression of carcinogenesis, exosomes are messengers for intercellular communication. Circular RNAs (circRNAs) are noncoding RNAs with functions that include regulation of the cell cycle and proliferation. However, the functions of exosomal circRNAs are not clear. The present research aimed to determine whether circRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 cells and become functionally active in the normal cells...
April 19, 2018: Cell Death & Disease
Qin He, Shuangyan Yang, Xiuge Gu, Mengying Li, Chunling Wang, Fulan Wei
Periodontal ligament stem cells (PDLSCs) are mesenchymal stem cells derived from dental tissues with multidirectional differentiation potential and excellent self-renewing ability. Recently, long noncoding RNAs (lncRNAs) have been shown to play important roles in MSC osteogenic differentiation. In this study, we found that taurine upregulated gene 1 (TUG1), an evolutionarily conserved and widely present lncRNA was significantly upregulated in osteogenically induced PDLSCs compared to their undifferentiated counterparts...
April 19, 2018: Cell Death & Disease
Zhaoyan Li, Yan Wang, Yadan Li, Wanqi Yin, Libin Mo, Xianghao Qian, Yiran Zhang, Guifen Wang, Fan Bu, Zhiling Zhang, Xiaofang Ren, Baochang Zhu, Chang Niu, Wei Xiao, Weiwei Zhang
The canonical Wnt/β-Catenin signaling pathway is widely involved in regulating diverse biological processes. Dysregulation of the pathway results in severe consequences, such as developmental defects and malignant cancers. Here, we identified Ube2s as a novel activator of the Wnt/β-Catenin signaling pathway. It modified β-Catenin at K19 via K11-linked polyubiquitin chain. This modification resulted in an antagonistic effect against the destruction complex/β-TrCP cascade-orchestrated β-Catenin degradation...
April 19, 2018: Cell Death & Disease
Shuai Yuan, Qingyun Liu, Zeyao Hu, Zhengyu Zhou, Guilu Wang, Chengying Li, Weijia Xie, Gang Meng, Ying Xiang, Na Wu, Long Wu, Zubin Yu, Li Bai, Yafei Li
Long non-coding RNAs (lncRNAs) have been involved in the process of cancer occurrence, progression, and treatment. Lung cancer-related lncRNAs are still an emerging field, thus we sought to identify novel functional lncRNAs as candidate targets in lung cancer. Here, we identified one novel lncRNA, MUC5B-AS1 (Ensembl: ENST00000532061.2). MUC5B-AS1 was upregulated in lung adenocarcinoma tissues compared with normal lung tissues. Moreover, MUC5B-AS1 promoted lung cancer cell migration and invasion in vitro and promoted lung cancer cell metastasis in vivo...
April 18, 2018: Cell Death & Disease
Huilin Ye, Quanbo Zhou, Shangyou Zheng, Guolin Li, Qing Lin, Lusheng Wei, Zhiqiang Fu, Bin Zhang, Yimin Liu, Zhihua Li, Rufu Chen
Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic cancer, partially owing to paracrine induction of VCAM-1 in pancreatic cancer cells. Reciprocally, VCAM-1-induced lactate production from pancreatic cancer cells with enhanced aerobic glycolysis activates macrophages to a TAM-like phenotype, forming a positive feedback loop...
April 18, 2018: Cell Death & Disease
Daniella Brasacchio, Rita A Busuttil, Tahereh Noori, Ricky W Johnstone, Alex Boussioutas, Joseph A Trapani
The loss of p300/CBP-associated protein (PCAF) expression is associated with poor clinical outcome in gastric cancer, and a potential bio-marker for invasive and aggressive tumors. However, the mechanism linking loss of PCAF to the onset of gastric cancer has not been identified. Given that PCAF and its binding partner transcriptional adaptor protein 3 (ADA3) were recently shown to regulate the intrinsic (mitochondrial) pathway to apoptosis via epigenetic regulation of phosphofurin acidic cluster sorting proteins 1 and 2 (PACS1, PACS2), we analyzed PCAF, ADA3, and PACS1/2 expression in 99 patient-matched surgical samples ranging from normal gastric mucosa, through pre-malignant chronic gastritis and intestinal metaplasia to stage I-III invasive cancers...
April 18, 2018: Cell Death & Disease
Pravat Kumar Parida, Barun Mahata, Abhisek Santra, Sohini Chakraborty, Zhumur Ghosh, Sanghamitra Raha, Anup Kumar Misra, Kaushik Biswas, Kuladip Jana
Resveratrol, a trans-stilbene polyphenolic compound and its synthetic analogs are widely used bioactive molecules due to their remarkable chemo-preventive potential. Here, we have identified a novel synthetic trans-stilbene compound, Z-DAN-11 ((Z)-3-(3, 4-dimethoxyphenyl)-2-(3, 4, 5-trimethoxyphenyl) acrylonitrile) which shows remarkable efficacy in blocking tumor growth and progression both in vitro and in vivo. Z-DAN-11 inhibits proliferation of cancer cells in vitro through microtubule depolymerization that induced G2/M arrest and consequently leads to apoptotic cell death...
April 18, 2018: Cell Death & Disease
Caixia Wang, Huaiqian Dai, Zhi Xiong, Qiancheng Song, Zhipeng Zou, Mangmang Li, Jing Nie, Xiaochun Bai, Zhenguo Chen
DEP domain containing mTOR-interacting protein (DEPTOR) was originally identified as an in vivo dual inhibitor of mechanistic target of rapamycin (mTOR). It was recently reported to be involved in renal physiology and pathology in vitro; however, its detailed roles and mechanisms in vivo are completely unknown. We observed that DEPTOR expression in the kidney was markedly increased on day 3 after cisplatin treatment, at which time cell apoptosis peaked, implicating DEPTOR in cisplatin-induced acute kidney injury (AKI)...
April 18, 2018: Cell Death & Disease
Qiang Zhang, Vladimir J N Bykov, Klas G Wiman, Joanna Zawacka-Pankau
The TP53 tumor suppressor gene is frequently inactivated in human tumors by missense mutations in the DNA binding domain. TP53 mutations lead to protein unfolding, decreased thermostability and loss of DNA binding and transcription factor function. Pharmacological targeting of mutant p53 to restore its tumor suppressor function is a promising strategy for cancer therapy. The mutant p53 reactivating compound APR-246 (PRIMA-1Met ) has been successfully tested in a phase I/IIa clinical trial. APR-246 is converted to the reactive electrophile methylene quinuclidinone (MQ), which binds covalently to p53 core domain...
April 18, 2018: Cell Death & Disease
Xiaoyang Li, Nicole A Seebacher, Cassandra Garbutt, Hangzhan Ma, Peng Gao, Tao Xiao, Francis J Hornicek, Zhenfeng Duan
Synovial sarcoma is a highly aggressive but rare form of soft tissue malignancy that primarily affects the extremities of the arms or legs, for which current chemotherapeutic agents have not been proven to be very effective. The cyclin-dependent kinase 4/6-retinoblastoma protein (CDK4/6-Rb) pathway of cell cycle control is known to be aberrant in a large proportion of cancers. Recently, CDK4 inhibitors have successfully been used pre-clinically for the treatment of many human cancers, and in 2015, following the success of clinical trials, the FDA approved the first selective CDK4/6 inhibitor, palbociclib, for the treatment of endocrine therapy resistant breast cancers...
April 18, 2018: Cell Death & Disease
Yuyao Wang, Dandan Zhang, Zhimin Tang, Yi Zhang, Huiqin Gao, Ni Ni, Bingqiao Shen, Hao Sun, Ping Gu
One of the primary obstacles in the application of retinal progenitor cells (RPCs) to the treatment of retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), is their limited ability to proliferate and differentiate into specific retinal neurons. In this study, we revealed that repressor element-1-silencing transcription factor (REST), whose expression could be transcriptionally and post-transcriptionally mediated by retinoic acid (RA, one isomeride of a vitamin A derivative used as a differentiation-inducing agent in many disease treatments), plays a pivotal role in the regulation of proliferation and differentiation of RPCs...
April 18, 2018: Cell Death & Disease
Yanan Wang, Wei Bao, Yuan Liu, Shiyu Wang, Shengjie Xu, Xi Li, Yanli Li, Sufang Wu
Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy, and cisplatin resistance is usually correlated with the poor prognosis of EOC. Increasing evidence indicates that the dysregulation of miRNAs is related to chemotherapy sensitivity. In this study, we revealed that miR-98-5p, a member of the let-7 family, was enriched in cisplatin-resistant EOC cells compared with cisplatin-sensitive cells, and could promote cisplatin resistance in EOC cells. Further studies showed that miR-98-5p could directly target the 3'-UTR of Dicer1 and suppress its expression, causing global miRNA downregulation...
April 18, 2018: Cell Death & Disease
Mara Salomé, Aoife Magee, Krisha Yalla, Shahzya Chaudhury, Evgenia Sarrou, Ruaidhrí J Carmody, Karen Keeshan
Trib2 pseudokinase is involved in the etiology of a number of cancers including leukaemia, melanoma, ovarian, lung and liver cancer. Both high and low Trib2 expression levels correlate with different types of cancer. Elevated Trib2 expression has oncogenic properties in both leukaemia and lung cancer dependent on interactions with proteasome machinery proteins and degradation of transcription factors. Here, we demonstrated that Trib2 deficiency conferred a growth and survival advantage both at steady state and in stress conditions in leukaemia cells...
April 18, 2018: Cell Death & Disease
Chao Jiang, Ping Xie, Ruxu Sun, Xiantao Sun, Guohua Liu, Sijia Ding, Meidong Zhu, Biao Yan, Qinghuai Liu, Xue Chen, Chen Zhao
Dedifferentiation of retinal pigment epithelium (RPE) cells and choroidal neovascularization (CNV) contributes to the pathogenesis of age-related macular degeneration (AMD). MicroRNAs (miRNAs) have crucial roles in AMD onset and progression. We thus aim to investigate the effects of miRNAs on RPE dedifferentiation and endothelium cell (EC) behavior, and analyze its downstream pathways. We have previously identified miR-302d-3p as the most downregulated miRNA signature along with RPE differentiation. Herein, in vitro study supported that miR-302d-3p induces RPE dedifferentiation typified by reduction of RPE characteristic markers, interrupts its phagocytosis, and promotes its migration, proliferation, and cell-cycle progression...
April 18, 2018: Cell Death & Disease
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