图书馆订阅: Guest
Begell Digital Portal Begell 数字图书馆 电子图书 期刊 参考文献及会议录 研究收集
环境病理学,毒理学和肿瘤学期刊
影响因子: 1.625 5年影响因子: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.2013007097
pages 41-51

Induction of miR-21-PDCD4 Signaling by Tungsten Carbide-Cobalt Nanoparticles in JB6 Cells Involves ROS-Mediated MAPK Pathways

Lichao Hou
Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40503; Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
Linda Bowman
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
Terence G. Meighan
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
Xianglin Shi
Division of Nutritional Sciences, Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY; Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY; Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY
Min Ding
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505

ABSTRACT

Tungsten carbide−cobalt (WC-Co) nanoparticle composites have wide applications because of their hardness and toughness. WC-Co was classified as "probably carcinogenic" to humans by the International Agency for Research on Cancer (IARC) in 2003. It is believed that the toxicity and carcinogenesis of WC-Co is associated with particle size. Recent studies demonstrated that the tumor suppressor gene programmed cell death 4 (PDCD4) and its upstream regulator miR-21 have been considered as oncogenes for novel cancer prevention or anticancer therapies. The present study examined the effects of WC-Co nanoparticles on miR-21-PDCD4 signaling in a mouse epidermal cell line (JB6 P+). The results showed that (i) exposure of JB6 cells to WC-Co stimulated a increase of miR-21 generation; (ii) WC-Co also caused inhibition of PDCD4, a tumor suppressor protein and downstream target of miR-21, expression in JB6 cells; (iii) inhibition of ERKs with ERK inhibitor U0126 significantly reversed WC-Cominus;induced PDCD4 inhibition, but inhibition of p38 with p38 inhibitor SB203580 did not; and (iv) ROS scavengers, N-acetyl-L-cysteine and catalase, blocked the inhibitory effect of WC-Co on PDCD4 expression, while superoxide dismutase promoted the inhibitory effect. These findings demonstrate that WC-Co nanoparticles induce miR-21 generation, but inhibit PDCD4 production, which may be mediated through ROS, especially endogenous H2O2, and ERK pathways. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of WC-Co−induced carcinogenesis.


Articles with similar content:

Tungsten Carbide-Cobalt Particles Activate Nrf2 and Its Downstream Target Genes in JB6 Cells Possibly by ROS Generation
Journal of Environmental Pathology, Toxicology and Oncology, Vol.29, 2010, issue 1
Xing-Dong Zhang, Jinshun Zhao, Min Ding, Linda Bowman, Vincent Castranova, Xianglin Shi
A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics
Critical Reviews™ in Oncogenesis, Vol.23, 2018, issue 5-6
Yuhao Wang, Benjamin Bonavida
Tyrosine Kinase Inhibitor AG490 Inhibits the Proliferation and Migration and Disrupts Actin Organization of Cancer Cells
Journal of Environmental Pathology, Toxicology and Oncology, Vol.32, 2013, issue 4
Kavita Shirsath, Rajiv P. Gude, Prachi Patil, Mohammad Zahid Kamran
Reactive Oxygen Species Mediate Cr(VI)-induced S Phase Arrest Through p53 in Human Colon Cancer Cells
Journal of Environmental Pathology, Toxicology and Oncology, Vol.31, 2012, issue 2
Young-Ok Son, Lijuan Sun, Zhuo Zhang, Jiankang Liu, Wenqi Li, Jia Luo, Hua Yao, Xin Wang
Inhibition of STAT3 Activation by RKIP in Colon Cancer
Forum on Immunopathological Diseases and Therapeutics, Vol.2, 2011, issue 1
Devasis Chatterjee, Erika L. Moen, Y. Eugene Chin