Tungsten Carbide‐Cobalt Nanoparticle induced miR‐21 Expression and PDCD4 Inhibition in JB6 Cells Involves a ROS‐ Mediated ERK Pathway (LB486)

Abstract

Tungsten Carbide‐Cobalt Nanoparticle induced miR‐21 Expression Involves ROS‐ Mediated ERK PathwayMin Ding1, Lichao Hou1,, Linda Bowman1, Terence G. Meighan1, Jun Liu2 Xianglin Shi3, 1Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505, 2Department of Physiology & Pharmacology, West Virginia University, Morgantown WV 26505 3Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40503Abstract Tungsten Carbide‐Cobalt (WC‐Co) nanoparticle composites have wide applications because of their hardness and toughness. WC‐Co has been classified as ‘probably carcinogenic’ to humans by the IARC. Earlier studies demonstrated that the tumor suppressor gene (PDCD4 and its upstream regulator miR‐21 may be considered as oncogenes for novel cancer prevention or anti‐cancer therapies. The present study examined the alterations of miR‐21‐PDCD4 signaling in JB6 cells after exposure to WC‐Co nanoparticles. The results showed that (1) WC‐Co caused PDCD4 inhibition in JB6 cells; (2) Exposure of cells to WC‐Co caused a significant increase of miR‐21, the upstream regulator of PDCD4, expression; (3) Inhibition of ERKs with U0126 reversed WC‐Co‐induced PDCD4 inhibition, but inhibition of p38 with SB203580 did not; and (4) ROS scavengers, N‐acetyl‐L‐cysteine and catalase, reversed the inhibitory effect of WC‐Co on PDCD4 expression, while superoxide dismutase promoted the inhibition. These findings demonstrate that WC‐Co nanoparticles induce miR‐21 expression and PDCD4 inhibition, 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.Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for occupational Safety and Health.Grant Funding Source: US Government