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Cell Death & Disease

Tiesuo Zhao, Tian Wei, Jing Guo, Yangeng Wang, Xiangyi Shi, Sheng Guo, Xiaolong Jia, Huijie Jia, Zhiwei Feng
Melanoma is one of the most aggressive skin cancers worldwide. Although there has been much effort toward improving treatment options over the past few years, there remains an urgent need for effective therapy. Immunotherapy combined with chemotherapy has shown great promise in clinical trials. Here, we studied the cooperative effects of the small molecule drug pimozide, which has a therapeutic effect in melanoma, and RNA interference (RNAi) targeting PD-1, an important immune checkpoint molecule involved in tumor immune escape...
February 18, 2019: Cell Death & Disease
Hanlin Ma, Yingwei Li, Xiangxiang Wang, Huan Wu, Gonghua Qi, Rongrong Li, Ning Yang, Min Gao, Shi Yan, Cunzhong Yuan, Beihua Kong
High-grade serous ovarian carcinoma (HGSOC) is the most lethal type of gynecologic malignancy. Chemoresistance is the main reason for the poor prognosis of HGSOC. PDZ-binding kinase (PBK) promotes the malignant progression of various carcinomas. However, the roles and clinical significance of PBK in HGSOC remain unclear. Here, we reported that PBK was overexpressed in HGSOC tissues and cell lines. High PBK expression was associated with a poor prognosis, metastasis, and cisplatin resistance of HGSOC. Overexpression of PBK promoted autophagy and enhanced cisplatin resistance via the ERK/mTOR signaling pathway...
February 18, 2019: Cell Death & Disease
Li Zhang, Zhihong Yang, Wendong Huang, Jianguo Wu
Cholestasis induces the hepatic long non-coding RNA H19, which promotes the progression of cholestatic liver fibrosis. However, microRNAs that are dysregulated by H19 during cholestasis remain elusive. Using miRNA-sequencing analysis followed by qPCR validation, we identified marked upregulation of eight members of the let-7 family in cholestatic livers by bile duct ligation (BDL) and H19 overexpression. In particular, the expression of let-7a-1/7d/7f-1 was highly induced in H19-BDL livers but decreased in H19KO-BDL livers...
February 18, 2019: Cell Death & Disease
Xiaoming Zhong, Bin Chen, Liang Yang, Zhiwen Yang
The original version of this Article contained errors in the author affiliations.
February 18, 2019: Cell Death & Disease
Tingting Yu, Xin Zhang, Haosong Shi, Jinge Tian, Lingling Sun, Xueming Hu, Wenqiang Cui, Dongping Du
Peripheral nerve injury causes neuropathic pain and microglia activation. P2Y12 receptors on microglia are thought to be a key player in the surveillance of the local environment, but whether or how these receptors are engaged in the cross-talk between microglia and neurons of the dorsal horn remain ambiguous. Using a rodent model of nerve injury-induced pain, we investigated the roles of P2Y12 in microglia activation, excitatory synaptic transmission, and nociceptive allodynia. We found that spinal nerve ligation (SNL) significantly increased the level of P2Y12 receptors specifically in the microglia of the ipsilateral dorsal horn...
February 18, 2019: Cell Death & Disease
Yi-Bing Sun, Hailin Zhao, Dong-Liang Mu, Wenwen Zhang, Jiang Cui, Lingzhi Wu, Azeem Alam, Dong-Xin Wang, Daqing Ma
Sepsis is life-threatening and often leads to acute brain damage. Dexmedetomidine, an α2 -adrenoceptor agonist, has been reported to possess neuroprotective effects against various brain injury but underlying mechanisms remain elusive. In this study, in vitro and in vivo models of sepsis were used to explore the effects of dexmedetomidine on the inflammasome activity and its associated glia pyroptosis and neuronal death. In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure...
February 18, 2019: Cell Death & Disease
Tanmay Majumdar, Shagun Sharma, Manmohan Kumar, Md Arafat Hussain, Namita Chauhan, Inderjeet Kalia, Amit Kumar Sahu, Vipin Singh Rana, Ruchi Bharti, Arun Kumar Haldar, Agam P Singh, Shibnath Mazumder
Recent studies have documented the diverse role of host immunity in infection by the protozoan parasite, Toxoplasma gondii. However, the contribution of the β-catenin pathway in this process has not been explored. Here, we show that AKT-mediated phosphorylated β-catenin supports T. gondii multiplication which is arrested in the deficiency of its phosphorylation domain at S552 position. The β-catenin-TCF4 protein complex binds to the promoter region of IRF3 gene and initiates its transcription, which was also abrogated in β-catenin knockout cells...
February 15, 2019: Cell Death & Disease
Anbang Wang, Yi Bao, Zhenjie Wu, Tangliang Zhao, Dong Wang, Jiazi Shi, Bing Liu, Shuhan Sun, Fu Yang, Linhui Wang, Le Qu
Long noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer (n = 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (n = 204), EGFR-AS1 was significantly upregulated in RCC tissues (P < 0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo...
February 15, 2019: Cell Death & Disease
Hongbo Zou, Qian Chen, Anmei Zhang, Songtao Wang, Hong Wu, Ye Yuan, Shuang Wang, Jing Yu, Mao Luo, Xianmei Wen, Wei Cui, Wenjuan Fu, Ruilian Yu, Lin Chen, Ming Zhang, Haitao Lan, Xia Zhang, Qichao Xie, Guoxiang Jin, Chuan Xu
Mitochondrial pyruvate carrier 1 (MPC1), a key factor that controls pyruvate transportation in the mitochondria, is known to be frequently dysregulated in tumor initiation and progression. However, the clinical relevance and potential molecular mechanisms of MPC1 in lung adenocarcinoma (LAC) progression remain to be illustrated. Herein, MPC1 was lowly expressed in LAC tissues and significantly associated with favorable survival of patients with LAC. Functionally, MPC1 markedly suppressed stemness, invasion, and migration in vitro and spreading growth of LAC cells in vivo...
February 15, 2019: Cell Death & Disease
Teresa Druck, Douglas G Cheung, Dongju Park, Francesco Trapasso, Flavia Pichiorri, Marco Gaspari, Tiziana Palumbo, Rami I Aqeilan, Eugenio Gaudio, Hiroshi Okumura, Rodolfo Iuliano, Cinzia Raso, Kari Green, Kay Huebner, Carlo M Croce
Fhit protein is lost in cancers of most, perhaps all, cancer types; when restored, it can induce apoptosis and suppress tumorigenicity, as shown in vitro and in mouse tumor models in vivo. Following protein cross-linking and proteomics analyses, we characterized a Fhit protein complex involved in triggering Fhit-mediated apoptosis. The complex includes the heat-shock chaperonin pair, HSP60/10, which is likely involved in importing Fhit into the mitochondria, where it interacts with ferredoxin reductase, responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin, in electron transport chain complex III...
February 15, 2019: Cell Death & Disease
Liangliang Shi, Xiaohua Hong, Li Ba, Xiaoxiao He, Yin Xiong, Qian Ding, Shengli Yang, Gang Peng
Mounting evidences indicated that long non-coding RNA is dysregulated and involved in the pathology of tumors. However, the role of lncRNAs in colorectal cancer (CRC) progression is not fully determined. Differentially expressed lncRNA profile in CRC was conducted by lncRNA microarray in 15 pairs of CRC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 106 pairs of tissues. The biological effect of lncRNA ZNFX1-AS1 was evaluated by in vitro and in vivo assays. The regulation between lncRNA ZNFX1-AS1 and miR-144 was evaluated by a series of experiments...
February 15, 2019: Cell Death & Disease
Yihao Sun, Di Zhang, Xiaowei Guo, Wenzhe Li, Chenglin Li, Jingjing Luo, Mingcheng Zhou, Lei Xue
The c-Jun N-terminal kinase (JNK) pathway plays essential roles in regulating a variety of physiological processes including cell migration and invasion. To identify critical factors that regulate JNK-dependent cell migration, we carried out a genetic screen in Drosophila based on the loss-of-cell polarity-triggered cell migration in the wing epithelia, and identified MKK3 licorne (lic) as an essential regulator of JNK-mediated cell migration and invasion. We found that loss of lic suppressed ptc > scrib-IR or ptc > Egr triggered cell migration in the wing epithelia, and Rasv12 /lgl-/- induced tumor invasion in the eye discs...
February 15, 2019: Cell Death & Disease
Ke Xu, Bin Han, Yang Bai, Xiu-Ying Ma, Zhen-Ni Ji, Yao Xiong, Shi-Kun Miao, Yuan-Yuan Zhang, Li-Ming Zhou
The global morbidity and mortality of colorectal cancer (CRC) are ranked the third among gastrointestinal tumors in the world. MiR-451a is associated with several types of cancer, including CRC. However, the roles and mechanisms of miR-451a in CRC have not been elucidated. BAP31 is a predicted target gene of miR-451a in our suppression subtractive hybridization library. Its relationship with miR-451a and function in CRC are unclear. We hypothesized that miR-451a could induce apoptosis through suppressing BAP31 in CRC...
February 15, 2019: Cell Death & Disease
KeShan Wang, TianBo Xu, HaiLong Ruan, HaiBing Xiao, Jingchong Liu, ZhengShuai Song, Qi Cao, Lin Bao, Di Liu, Cheng Wang, Gong Cheng, HuaGeng Liang, ZhaoHui Chen, HongMei Yang, Ke Chen, XiaoPing Zhang
Notwithstanding the researches on biomarkers and targeted therapies in renal cell carcinomas (RCC) have made progress in the last decades, the application of the biomarkers and targeted therapy agents for RCC in clinic are restricted because of their limitation or side effects. Liver X receptors (LXRs) and the NLRP3 inflammasome have been the research hotspots in recent years. In our study, we integrated bioinformatics analysis, molecular biology experiments and biological function experiments to study the roles of LXRα and the NLRP3 inflammasome in RCC...
February 15, 2019: Cell Death & Disease
Behnaz Ahangarian Abhari, Nicole McCarthy, Marie Le Berre, Michelle Kilcoyne, Lokesh Joshi, Patrizia Agostinis, Simone Fulda
Since Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation...
February 15, 2019: Cell Death & Disease
Jun-Yan Liu, Lei Jiang, Tao He, Jia-Jia Liu, Jun-Yan Fan, Xian-Hui Xu, Bo Tang, Yan Shi, Yong-Liang Zhao, Feng Qian, Yan Wang, You-Hong Cui, Pei-Wu Yu
Aberrant expression of neuropilin and tolloid-like 2 (NETO2) has been observed during the progression of some human carcinomas. However, the expression pattern and clinical relevance of NETO2 in gastric cancer (GC) remain to be elucidated. In this study, we found that NETO2 expression was higher in GC tissues compared with paired non-cancerous tissues. Moreover, the expression of NETO2 was positively correlated with clinical stage, invasion depth, lymph node metastasis, and tumor size, but inversely correlated with overall and disease-free survival rates...
February 15, 2019: Cell Death & Disease
Wenli Xu, Ye Wu, Li Wang, Yan Bai, Yunhui Du, Yang Li, Ning Cao, Yuhui Zhao, Youyi Zhang, Huirong Liu
Therapeutic adoptive transfer of natural regulatory T cells (nTreg, CD4+ CD25+ Foxp3+ T cells) or in vivo selective expansion of nTreg cells has been demonstrated to improve the cardiac function in various cardiovascular disease models. The differentiation of nTreg cells is mediated by catecholamines via β1 -adrenergic receptor (β1 -AR) activation. Autoantibody against β1 -adrenoceptor (β1 -AA) as a β1 -AR agonist is closely associated with the occurrence and deterioration of cardiac dysfunction. However, whether β1 -AA has any impact on nTreg cells has not been reported...
February 15, 2019: Cell Death & Disease
Jeong-Hwa Baek, Hong Shik Yun, Gyoo Taik Kwon, Janet Lee, Ju-Young Kim, Yunhui Jo, Jae-Min Cho, Chang-Woo Lee, Jie-Young Song, Jiyeon Ahn, Jae-Sung Kim, Eun Ho Kim, Sang-Gu Hwang
Current lung cancer treatments are far from satisfactory; thus, finding novel treatment targets is crucial. We recently identified procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), which is involved in fibrosis and tissue remodeling as a radioresistance-related protein in lung cancer cells; however, its mechanism is unclear. In this study, we designed human PLOD3-specific short interfering (si)RNAs and tested their effects on tumor growth inhibition in vitro and in vivo. PLOD3 knockdown overcame chemoresistance and decreased radioresistance by inducing caspase-3-dependent apoptosis in lung cancer cells...
February 15, 2019: Cell Death & Disease
Hao Yan, Jia Wen, Tuo Zhang, Wenying Zheng, Meina He, Kun Huang, Qirui Guo, Qian Chen, Yi Yang, Guangcun Deng, Jinrui Xu, Zhiqing Wei, Hua Zhang, Guoliang Xia, Chao Wang
In mammals, female fecundity is determined by the size of the primordial follicle (PF) pool, which is established during the perinatal period. As a non-renewable resource, the preservation of dormant PFs is crucial for sustaining female reproduction throughout life. Although studies have revealed that several oocyte-derived functional genes and pathways, such as newborn ovary homeobox (NOBOX) and 3-phosphoinositide-dependent protein kinase-1, participate in maintaining the PF pool, our understanding of the underlying molecular mechanisms is still incomplete...
February 15, 2019: Cell Death & Disease
Shuping Yang, Xiang Gao, Yihong He, Yuzhu Hu, Bocheng Xu, Zhiqiang Cheng, Mingli Xiang, Yongmei Xie
α-Mangostin (αM), a traditional natural product with promising application of treating a series of diseases, was limited use in clinical due to its hydrophobicity. Herein, MPEG-PCL nanomicelles were used to embed the αM for resolving hydrophobicity and improving the anti-melanoma effect of the αM. The anti-melanoma activity and potential mechanisms of biodegradable αM/MPEG-PCL nanomicelles were investigated. The αM/MPEG-PCL nanomicelles possessed a stronger effect on anti-melanoma compared to the free αM both in vitro and in vivo with a low cytotoxicity in non-tumor cell lines...
February 15, 2019: Cell Death & Disease
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