Browse

The effect of RNAi silencing of p62 using an osmotic polysorbitol transporter on autophagy and tumorigenesis in lungs of K-ras(LA1) mice

Cited 16 time in Web of Science Cited 16 time in Scopus
Authors
Islam, Mohammad Ariful; Shin, Ji-Young; Yun, Cheol-Heui; Cho, Chong-Su; Seo, Hwi Won; Chae, Chanhee; Cho, Myung-Haing
Issue Date
2014-02
Citation
Biomaterials, Vol.35 No.5, pp.1584-1596
Keywords
Autophagy activationTumor suppressionPolysorbitol transporterp62 silencingK-ras(LA1) mice
Abstract
Treating cancer patients by conventional chemotherapy to achieve prolonged survival still remains complicated. Autophagy is a topic of considerable interest in recent times, as it may contribute greatly to tumor suppression. Recent studies indicate that autophagy-deficient cells accumulate high levels of p62, an ubiquitin-binding scaffold protein, involved greatly in tumorigenesis. Here, we synthesized an osmotically active polysorbitol-mediated transporter (PSMT) to downregulate p62 using an RNAi strategy and described the mechanism of how p62 silencing using PSMT/siRNA p62 system activates autophagy and contributes to tumor suppression in the lungs of K-ras(LA1) mice. Downregulation of p62 by PSMT/siRNA p62 activated autophagy confirmed by the formation of autophagosomes and swelling of Golgi apparatus with a decreasing level of GM130, a cis-Golgi matrix protein. Activation of osmotic PSMT-mediated autophagy remarkably reduced the size and number of tumors by suppressing proliferative cell nuclear antigen, cluster of differentiation 31, and vascular endothelial growth factor levels. Furthermore, an increase in apoptosis was observed in the lungs of PSMT/siRNA p62-delivered mice. (C) 2013 Elsevier Ltd. All rights reserved.
ISSN
0142-9612
URI
https://hdl.handle.net/10371/172336
DOI
https://doi.org/10.1016/j.biomaterials.2013.11.010
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse