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Tumor suppressor

Yun Bai, Jia Wang, Jing Han, Xiao-Li Xie, Cheng-Guang Ji, Jie Yin, Lei Chen, Cun-Kai Wang, Xiao-Yu Jiang, Wei Qi, Hui-Qing Jiang
BACKGROUND AND AIMS: BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. METHODS: BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice...
October 22, 2016: Molecular Carcinogenesis
Li Zhang, Zhihong Yang, Jocelyn Trottier, Olivier Barbier, Li Wang
: Bile acids (BAs) play critical physiological functions in cholesterol homeostasis and deregulation of BA metabolism causes cholestatic liver injury. Maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor, however its basic hepatic function remains elusive. Using RNA pull-down with biotin-labeled sense or anti-sense MEG3RNA followed by mass spectrometry, we identified RNA binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interaction protein and validated their interaction by RNA immunoprecipitation (RIP)...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Fei-Fei Wang, Song Wang, Wen-Hua Xue, Jing-Liang Cheng
microRNAs (miRNAs), a family of small non-coding RNA molecules, are implicated in cancer growth and progression. In the present study, we examined the expression and biological roles of miR-590 in non-small cell lung cancer (NSCLC). Compared to normal lung tissues, miR-590 expression was downregulated in primary NSCLCs and, to a greater extent, in corresponding brain metastases. NSCLC cell lines with high metastatic potential had significantly (P < 0.05) lower levels of miR-590 than those with low metastatic potential...
October 21, 2016: Molecular and Cellular Biochemistry
Jolanda van Hengel, Celine Van den Broeke, Tim Pieters, Louis Libbrecht, Ilse Hofmann, Frans van Roy
p120 catenin (p120ctn) is required for the stability of classic cadherins at the cell surface and is thought to play a central role in modulating cell-cell adhesion. Cytoplasmic p120ctn promotes cell motility, and probably other activities, by modulating the activities of RhoA, Rac and Cdc42. E-cadherin is expressed in periportal but not in perivenous hepatocytes. In contrast, all hepatocytes of normal mouse liver express N-cadherin. Cholangiocytes express exclusively E-cadherin. Mice with p120ctn ablation in hepatocytes and cholangiocytes (p120LiKO mice) were generated by Cre-loxP technology...
October 15, 2016: European Journal of Cell Biology
Srikanth Appikonda, Kaushik N Thakkar, Michelle Craig Barton
Tripartite Motif-containing protein 24 (TRIM24) functions as an E3 ligase targeting p53 for ubiquitination, a histone 'reader' that interacts with a specific signature of histone post-translational modifications and a co-regulator of nuclear receptor-regulated transcription. Although mouse models of Trim24 depletion suggest that TRIM24 may be a liver-specific tumor suppressor, several studies show that human TRIM24 is an oncogene when aberrantly over expressed. This review focuses on the mechanisms of TRIM24 functions in oncogenesis and metabolic reprogramming, which underlie recent interest in therapeutic targeting of aberrant TRIM24 in human cancers...
March 2016: Drug Discovery Today. Technologies
Mingdi Zhang, Wei Gong, Bin Zuo, Bingfeng Chu, Zhaohui Tang, Yong Zhang, Yong Yang, Di Zhou, Mingzhe Weng, Yiyu Qin, Mingzhe Ma, Alex Jiang, Fei Ma, Zhiwei Quan
Cytokine is a key molecular link between chronic inflammation and gallbladder cancer (GBC) progression. The potential mechanism of cytokine-associated modulation of microRNAs (miRNAs) expression in GBC progression is not fully understood. In this study, we investigated the biological effects and prognostic significance of interleukin-6 (IL-6) -induced miRNAs in the development of GBC. We identify that inflammatory cytokine, IL-6 promotes proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GBC both in vitro and in vivo...
October 15, 2016: Oncotarget
Katharina Meier, Stefan K Drexler, Franziska C Eberle, Karine Lefort, Amir S Yazdi
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC...
2016: PloS One
Yong-Sik Bong, Shahin Assefnia, Therese Tuohy, Deborah W Neklason, Randall W Burt, Jaeil Ahn, Hao-Wen J Jiang, Stephen W Byers
Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-)...
October 19, 2016: Oncotarget
Di-Yi Wang, Shu-Hong An, Lei Liu, Shan-Shan Bai, Kai-Xiang Wu, Rong Zhu, Zhao-Jin Wang
We previously showed that hepatitis B virus (HBV) X protein (HBx) could promote the trimethylation of histone H3 lysine 9 (H3K9me3) to repress tumor suppressor genes in hepatocellular carcinoma (HCC). In this work, we analyze 23,148 human promoters using ChIP-chip to determine the effects of HBx on H3K9me3 enrichments in hepatoma cells with transfection of HBx-expressing plasmid. Immunohistochemistry for HBx and H3K9me3 was performed in 21 cases of HBV-associated HCC tissues. We identified that H3K9me3 immunoreactivity was significantly correlated with HBx staining in HCC tissues...
October 19, 2016: Oncotarget
Meital Charni, Ronit Aloni-Grinstein, Alina Molchadsky, Varda Rotter
Regeneration and tumorigenesis share common molecular pathways, nevertheless the outcome of regeneration is life, whereas tumorigenesis leads to death. Although the process of regeneration is strictly controlled, malignant transformation is unrestrained. In this review, we discuss the involvement of TP53, the major tumor-suppressor gene, in the regeneration process. We point to the role of p53 as coordinator assuring that regeneration will not shift to carcinogenesis. The fluctuation in p53 activity during the regeneration process permits a tight control...
October 21, 2016: Cell Death and Differentiation
Junyong Zhang, Zuojin Liu, Zhengrong Lian, Rui Liao, Yi Chen, Yi Qin, Jinlong Wang, Qing Jiang, Xiaobo Wang, Jianping Gong
Monoacylglycerol lipase (MAGL) is a key enzyme in lipid metabolism that is demonstrated to be involved in tumor progression through both energy supply of fatty acid (FA) oxidation and enhancing cancer cell malignance. The aim of this study was to investigate whether MAGL could be a potential therapeutic target and prognostic indicator for hepatocellular carcinoma (HCC). To evaluate the relationship between MAGL levels and clinical characteristics, a tissue microarray (TMA) of 353 human HCC samples was performed...
October 21, 2016: Scientific Reports
Chao Shang, Yan Guo, Yang Hong, Yi-Xue Xue
Tumour suppressor candidate 7 (TUSC7) is a novel tumor suppressor gene generating long non-coding RNA (lncRNAs) in several types of human cancers. The expression and function of TUSC7 in human brain glioma has yet to be elucidated. In this study, TUSC7 was poorly expressed in tissues and cell lines of glioma, and the lower expression was correlated with glioma of the worse histological grade. Moreover, TUSC7 is a prognostic biomarker of glioma patients. Up-regulation of TUSC7 suppressed cellular proliferation and invasion of glioma cells, and accelerated cellular apoptosis...
2016: Frontiers in Cellular Neuroscience
Rui Zhang, Chang Liu, Yahan Niu, Ying Jing, Haiyang Zhang, Jin Wang, Jie Yang, Ke Zen, Junfeng Zhang, Chen-Yu Zhang, Donghai Li
The DNA damage response is critical for maintaining genome integrity and preventing damage to DNA due to endogenous and exogenous insults. Mitomycin C (MMC), a potent DNA cross-linker, is used as a chemotherapeutic agent because it causes DNA inter-strand cross-links (DNA ICLs) in cancer cells. While many microRNAs, which may serve as oncogenes or tumor suppressors, are grossly dysregulated in human cancers, little is known about their roles in MMC-treated lung cancer. Here, we report that miR-128-3p can attenuate repair of DNA ICLs by targeting SPTAN1 (αII Sp), resulting in cell cycle arrest and promoting chromosomal aberrations in lung cancer cells treated with MMC...
September 28, 2016: Oncotarget
Hiroko Mataki, Naohiko Seki, Keiko Mizuno, Nijiro Nohata, Kazuto Kamikawaji, Tomohiro Kumamoto, Keiichi Koshizuka, Yusuke Goto, Hiromasa Inoue
Patients with lung adenocarcinoma may benefit from recently developed molecular targeted therapies. However, analogous advanced treatments are not available for patients with lung squamous cell carcinoma (lung SCC). The survival rate of patients with the advanced stage of lung SCC remains poor. Exploration of novel lung SCC oncogenic pathways might lead to new treatment protocols for the disease. Based on this concept, we have identified microRNA- (miRNA) mediated oncogenic pathways in lung SCC. It is well known that miR-145-5p (the guide strand) functions as a tumor suppressor in several types of cancer...
September 27, 2016: Oncotarget
Yong Lin, Xin Ge, Yiyang Wen, Zhu-Mei Shi, Qiu-Dan Chen, Min Wang, Ling-Zhi Liu, Bing-Hua Jiang, Yuan Lu
Pancreatic adenocarcinoma is one of the most leading causes of cancer-related deaths worldwide. Although recent advances provide various treatment options, pancreatic adenocarcinoma has poor prognosis due to its late diagnosis and ineffective therapeutic multimodality. Gemcitabine is the effective first-line drug in pancreatic adenocarcinoma treatment. However, gemcitabine chemoresistance of pancreatic adenocarcinoma cells has been a major obstacle for limiting its treatment effect. Our study found that p70S6K1 plays an important role in gemcitabine chemoresistence...
September 27, 2016: Oncotarget
Kwong-Fai Wong, Angela M Liu, Wanjin Hong, Zhi Xu, John M Luk
The Hippo pathway regulates the down-stream target Yes-associated protein (YAP) to maintain organ homeostasis, which is commonly inactivated in many types of cancers. However, how cell adhesion dysregulates the Hippo pathway activating YAP oncogene in hepatocellular carcinoma (HCC) remains unclear. Our findings demonstrate that α2β1 integrin (but not other β1 integrins) expressed in HCC cells, after binding to collagen extracellular matrix, could inhibit MST1 kinase phosphorylation and activate YAP pro-oncogenic activities...
October 19, 2016: Oncotarget
Ion Cristobal, Blanca Torrejón, Manuel Pedregal, Federico G Rojo, Jesús García-Foncillas
Dear Editor, We have read with great interest the recent published manuscript by Caiazza et al. (2016), which provides novel exciting findings about the potential therapeutic value of enzalutamide in patients with androgen receptor (AR)-positive triple negative breast cancer (TNBC). Some previous studies have shown promising antitumor effects of this drug in breast tumors. Thus, enzalutamide-mediated AR inhibition has been reported to reduce proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis of TNBC cells in vitro and decrease viability of TNBC xenografts in vivo (Cochrane et al...
October 20, 2016: Endocrine-related Cancer
Verena Stahn, Inga Nagel, Susan Fischer-Huchzermeyer, Florian Oyen, Reinhard Schneppenheim, Stefan Gesk, Axel Bohring, Levan Chikobava, Peter Young, Burkhard Gess, Mathias Werner, Volker Senner, Anja Harder
Neurofibromas and schwannomas are benign Schwann cell-derived peripheral nerve sheath tumors arising sporadically and within neurofibromatoses. Multiple tumors are a hallmark of neurofibromatosis type 1 (NF1) and type 2 (NF2) and schwannomatosis. Neurofibromas in NF1 and schwannomas in NF2 or schwannomatosis are defined by distinctive molecular hits. Among these, multiple hybrid neurofibromas/schwannomas may also appear, not yet being defined by a molecular background. We therefore performed molecular analysis of 22 hybrid neurofibromas/schwannomas using array comparative genomic hybridization, immunohistochemistry, quantitative RT-PCR, and functional analyses of cultured Schwann cells...
October 17, 2016: American Journal of Pathology
E Fehri, E Ennaifer, R Bel Haj Rhouma, L Guizani-Tabbane, I Guizani, S Boubaker
Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis...
July 2016: Current Research in Translational Medicine
Y Liu, X Tan, Z Wang, Y Li, M Gao, Y Li, Z Fang, Y Sun, L Zhang, X Wang, Z Wei
OBJECTIVE: Adenomyosis is a common benign gynecological disease which has some malignant behaviors. Programmed cell death 4 (PDCD4) is a newly identified tumor suppressor gene which lowly expresses in various cancers. However, the expression status of PDCD4 in endometrium of adenomyosis patients has not been investigated. The aim of this study is to assess the expression levels of PDCD4 in endometrium of normal controls and adenomyosis patients. METHODS: The expression of PDCD4 in endometrium of normal controls and eutopic or ectopic endometrium of patients with adenomyosis was evaluated with quantitative real-time PCR, western blot and immunohistochemistry...
July 2016: Current Research in Translational Medicine
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