title: Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide. However, the treatment of patients with HCC is particularly challenging. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a potential suppressor of several types of tumors, but the delivery of long RNA remains problematic, limiting its applications. In the present study, we designed a novel delivery system based on MS2 virus-like particles (VLPs) crosslinked with GE11 polypeptide. This vector was found to be fast, effective and safe for the targeted delivery of lncRNA MEG3 RNA to the epidermal growth factor receptor (EGFR)-positive HCC cell lines without the activation of EGFR downstream pathways, and significantly attenuated both in vitro and in vivo tumor cell growth. Our study also revealed that the targeted delivery was mainly dependent on clathrin-mediated endocytosis and MEG3 RNA suppresses tumor growth mainly via increasing the expression of p53 and its downstream gene GDF15, but decreasing the expression of MDM2. Thus, this vector is promising as a novel delivery system and may facilitate a new approach to lncRNA based cancer therapy.
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Le
authors.initials: L
authors.lastname: Chang
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Guojing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Jia
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.|Peking University Fifth School of Clinical Medicine, Beijing, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.
authors.forename: Yanxi
authors.initials: Y
authors.lastname: Han
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.
authors.forename: Guigao
authors.initials: G
authors.lastname: Lin
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Li
authors.affiliation: National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Lunan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D049109:Cell Proliferation; D004337:Drug Carriers; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D017909:Levivirus / Q000737:chemistry*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000008:administration & dosage / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D004337:Drug Carriers; C498907:MEG3 non-coding RNA, human; D010446:Peptide Fragments; D062085:RNA, Long Noncoding; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: GE11; MS2 virus-like particles; epidermal growth factor receptor; hepatocellular carcinoma; maternally expressed gene 3