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Xuemei Zhang, Chuan Li, Da Wang, Qu Chen, Chang-Long Li, Hong-Jiang Li
Epigenetic modifications are critical determinants in tumor initiation and progression. This study aims to detect the promoter methylation status and the mRNA expression levels of ATG2B, ATG4D, ATG9A and ATG9B, and then to explore their relationship in invasive ductal carcinomas (IDCs) and matched normal tissues (MNTs) of the breast. Methylation was observed as follows: 61.0% in ATG2B, 46.8% in ATG4D, 56.4% in ATG9A, and 74.0% in ATG9B of IDCs. Meanwhile, their mRNA expression levels of the IDCs was lower than that of the MNTs (P<0...
September 30, 2016: Gene
Xue-mei Zhang, Hong-jiang Li, Da Wang, Chuan Li, Qu Chen, Chang-long Li
OBJECTIVE: To investigate the expressions and clinical significance of autophagy-related gene 2B (ATG2B), autophagy-related gene 4D (ATG4D), autophagy-related gene 9B (ATG9B) in breast cancer cell lines and breast cancer. METHODS: Cancer Browser screening was applied to study the differential expressions of ATG2B, ATG4D, ATG9B genes in breast cancer. Quantitative Real-time PCR was used to measure the expressions of these three genes in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435S and ZR-75-30) as well as 83 cases of breast cancer samples with paired normal breast tissues...
March 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Chandra B Lebovitz, A Gordon Robertson, Rodrigo Goya, Steven J Jones, Ryan D Morin, Marco A Marra, Sharon M Gorski
Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium...
2015: Autophagy
Meng Shen, Wei-Ming Duan, Meng-Yao Wu, Wen-Jie Wang, Lu Liu, Meng-Dan Xu, Jie Zhu, Dao-Ming Li, Qi Gui, Lian Lian, Fei-Ran Gong, Kai Chen, Wei Li, Min Tao
Breast cancer is one of the most common cancers affecting women worldwide. Conventional chemotherapy is still one of the major approaches to the treatment of breast cancer. Autophagy, also termed as type II programmed cell death (PCD), exhibits either a protumorigenic or antitumorigenic function. In the present study, we investigated whether autophagy could be involved in the effect of chemotherapy against breast cancer. Epirubicin, docetaxel, methotrexate, cyclophosphamide, fluorouracil (5-FU) and cisplatin were applied in the present investigation...
July 2015: Oncology Reports
Kaisa Kyöstilä, Pernilla Syrjä, Vidhya Jagannathan, Gayathri Chandrasekar, Tarja S Jokinen, Eija H Seppälä, Doreen Becker, Michaela Drögemüller, Elisabeth Dietschi, Cord Drögemüller, Johann Lang, Frank Steffen, Cecilia Rohdin, Karin H Jäderlund, Anu K Lappalainen, Kerstin Hahn, Peter Wohlsein, Wolfgang Baumgärtner, Diana Henke, Anna Oevermann, Juha Kere, Hannes Lohi, Tosso Leeb
Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine neurodegenerative disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus and behavioral changes. Histological examination revealed unique pathological changes, including profound neuronal cytoplasmic vacuolization in the nervous system, as well as spheroid formation and cytoplasmic aggregation of vacuoles in secretory epithelial tissues and mesenchymal cells...
April 2015: PLoS Genetics
Krishna K Singh, Bobby Yanagawa, Adrian Quan, Rixin Wang, Ankit Garg, Rishad Khan, Yi Pan, Mark D Wheatcroft, Fina Lovren, Hwee Teoh, Subodh Verma
OBJECTIVE: Autophagy is an evolutionary conserved adaptive response that is believed to promote cell survival in response to stressful stimuli via recycling of precursors derived from the degradation of endogenous cellular components. The autophagic molecular machinery is controlled by a large family of autophagy-related genes (ATGs) and downstream regulators. We sought to define the autophagy gene fingerprint associated with human ischemia and reperfusion (IR) injury using an intraoperative model developed by Sellke and colleagues...
March 2014: Journal of Thoracic and Cardiovascular Surgery
Virginie M S Betin, Belinda K Singleton, Stephen F Parsons, David J Anstee, Jon D Lane
Wholesale depletion of membrane organelles and extrusion of the nucleus are hallmarks of mammalian erythropoiesis. Using quantitative EM and fluorescence imaging we have investigated how autophagy contributes to organelle removal in an ex vivo model of human erythroid differentiation. We found that autophagy is induced at the polychromatic erythroid stage, and that autophagosomes remain abundant until enucleation. This stimulation of autophagy was concomitant with the transcriptional upregulation of many autophagy genes: of note, expression of all ATG8 mammalian paralog family members was stimulated, and increased expression of a subset of ATG4 family members (ATG4A and ATG4D) was also observed...
June 1, 2013: Autophagy
Yonghua Xu, Yong An, Yun Wang, Changhe Zhang, Hai Zhang, Changjun Huang, Hao Jiang, Xuehao Wang, Xiangcheng Li
Hepatocellular carcinoma (HCC) ranks third in cancer-related mortality due to late diagnosis and poor treatment options. Autophagy is a lysosome-mediated protein and organelle degradation process which is characterized by the formation of double-membrane vesicles, known as autophagosomes. Increasing evidence reveals that autophagy functions as a survival mechanism in liver cancer cells against drug-induced apoptosis. In this study, we found that autophagy was suppressed by miR-101 in the HCC cell line HepG2...
May 2013: Oncology Reports
Virginie M S Betin, Thomas D B MacVicar, Stephen F Parsons, David J Anstee, Jon D Lane
The Atg4 cysteine proteases play crucial roles in the processing of Atg8 proteins during autophagy, but their regulation during cellular stress and differentiation remains poorly understood. We have found that two Atg4 family members--Atg4C and Atg4D--contain cryptic mitochondrial targeting sequences immediately downstream of their canonical (DEVD) caspase cleavage sites. Consequently, caspase-cleaved Atg4D (ΔN63 Atg4D) localizes to the mitochondrial matrix when expressed in mammalian cells, where it undergoes further processing to a ~42 kDa mitochondrial form...
April 2012: Autophagy
Marko Brinar, Séverine Vermeire, Isabelle Cleynen, Bart Lemmens, Xavier Sagaert, Liesbet Henckaerts, Gert Van Assche, Karel Geboes, Paul Rutgeerts, Gert De Hertogh
BACKGROUND AND AIMS: Granulomas are a characteristic microscopic finding in Crohn's disease. Their clinical significance is controversial and their pathogenesis is unknown, but impaired processing of bacterial components has been suggested. Autophagy is a fundamental process involved in the elimination of intracellular bacteria. Genetic variants in autophagy genes IRGM and ATG16L1 have been associated with susceptibility to Crohn's disease. We therefore investigated whether variants in autophagy genes contribute to granuloma formation...
February 2012: Journal of Crohn's & Colitis
Lisa B Frankel, Jiayu Wen, Michael Lees, Maria Høyer-Hansen, Thomas Farkas, Anders Krogh, Marja Jäättelä, Anders H Lund
Autophagy is an evolutionarily conserved mechanism of cellular self-digestion in which proteins and organelles are degraded through delivery to lysosomes. Defects in this process are implicated in numerous human diseases including cancer. To further elucidate regulatory mechanisms of autophagy, we performed a functional screen in search of microRNAs (miRNAs), which regulate the autophagic flux in breast cancer cells. In this study, we identified the tumour suppressive miRNA, miR-101, as a potent inhibitor of basal, etoposide- and rapamycin-induced autophagy...
November 16, 2011: EMBO Journal
Min Li, Yifeng Hou, Jinsong Wang, Xiaoyun Chen, Zhi-Ming Shao, Xiao-Ming Yin
The Atg4 cysteine proteases are required for processing Atg8 for the latter to be conjugated to phosphatidylethanolamine on autophagosomal membranes, a key step in autophagosome biogenesis. Notably, whereas there are only one atg4 and one atg8 gene in the yeast, the mammals have four Atg4 homologues and six Atg8 homologues. The Atg8 homologues seem to play different roles in autophagosome biogenesis, and previous studies had indicated that they could be differentially processed by Atg4 homologues. The present study provided the first detailed kinetics analysis of all four Atg4 homologues against four representative Atg8 homologues...
March 4, 2011: Journal of Biological Chemistry
Virginie M S Betin, Jon D Lane
The Atg4 family of endopeptidases regulates autophagosome biogenesis by priming newly synthesized Atg8 to enable covalent attachment of phosphatidylethanolamine, and by delipidating Atg8 at the lysosomal fusion step. Control of Atg4 activity is therefore crucial, although little is known about how these molecules are regulated in living cells. We have found that one human Atg4 family member (Atg4D) is cleaved at DEVD(63)K by caspase-3 during apoptosis. Importantly, our studies suggest that native Atg4D is enzymatically inactive, but gains GABARAP-L1 priming/delipidation activity following caspase cleavage...
October 2009: Autophagy
Virginie M S Betin, Jon D Lane
Autophagy is an important catabolic process with roles in cell survival and cell death. It sequesters cytosol and organelles within double-membrane autophagosomes that deliver their contents to lysosomes for degradation. Autophagosome biogenesis is coordinated by the autophagy-related protein 4 (Atg4) family of C54 endopeptidases (Atg4A-Atg4D). These enzymes prime and then later delipidate the autophagosome marker, Atg8. Here, we show that one family member, Atg4D, is cleaved by caspase-3 in vitro and in apoptotic cells...
July 15, 2009: Journal of Cell Science
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