title: The effect of RNAi silencing of p62 using an osmotic polysorbitol transporter on autophagy and tumorigenesis in lungs of K-rasLA1 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 K-ras(LA1) mice.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Mohammad Ariful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea. Electronic address: chocs@snu.ac.kr.
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hwi Won
authors.initials: HW
authors.lastname: Seo
authors.affiliation: Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Chanhee
authors.initials: C
authors.lastname: Chae
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea; Graduate School of Convergence Science and Technology, Suwon 443-270, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Republic of Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D063646:Carcinogenesis; D002352:Carrier Proteins / Q000378:metabolism*; D020868:Gene Silencing; D011905:Genes, ras; D006056:Golgi Apparatus / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D034622:RNA Interference; D013012:Sorbitol / Q000378:metabolism*; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C490981:Gtf2h1 protein, mouse; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D013012:Sorbitol
keywords: Autophagy activation; K-ras(LA1) mice; Polysorbitol transporter; Tumor suppression; p62 silencing