Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma

被引：85

作者：

Chang, Le ^{[1
,2
]}

Wang, Guojing ^{[1
,2
]}

Jia, Tingting ^{[3
]}

Zhang, Lei ^{[1
,4
]}

Li, Yulong ^{[1
,2
]}

Han, Yanxi ^{[1
]}

Zhang, Kuo ^{[1
,2
]}

Lin, Guigao ^{[1
]}

Zhang, Rui ^{[1
]}

Li, Jinming ^{[1
,2
]}

Wang, Lunan ^{[1
,2
]}

机构：

[1] Beijing Hosp, Natl Ctr Clin Labs, Beijing, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China

[3] Capital Med Univ, Beijing Chaoyang Hosp, Dept Clin Lab, Beijing, Peoples R China

[4] Peking Univ, Sch Clin Med 5, Beijing 100871, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 17期

关键词：

hepatocellular carcinoma; maternally expressed gene 3; MS2 virus-like particles; epidermal growth factor receptor; GE11; GROWTH-FACTOR RECEPTOR; EXTERNAL QUALITY ASSESSMENT; MICRORNA DELIVERY-SYSTEM; CELL-PROLIFERATION; COAT PROTEIN; CANCER; EXPRESSION; AFFINITY; LIGAND; P53;

D O I：

10.18632/oncotarget.8115

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：23988 / 24004

页数：17

共 57 条

[1] Efficacy of an EGFR-Specific Peptide against EGFR-Dependent Cancer Cell Lines and Tumor Xenografts [J].

Ahsan, Aarif ;

Ramanand, Susmita G. ;

Bergin, Ingrid L. ;

Zhao, Lilli ;

Whitehead, Christopher E. ;

Rehemtulla, Alnawaz ;

Ray, Dipankar ;

Pratt, William B. ;

Lawrence, Theodore S. ;

Nyati, Mukesh K. .

NEOPLASIA, 2014, 16 (02) :105-+

[2] Cyclooxygenase inhibitors regulate the expression of a TGF-β superfamily member that has proapoptotic and antitumorigenic activities [J].

Baek, SJ ;

Kim, KS ;

Nixon, JB ;

Wilson, LC ;

Eling, TE .

MOLECULAR PHARMACOLOGY, 2001, 59 (04) :901-908

[3] MEG3 imprinted gene contribution in tumorigenesis [J].

Benetatos, Leonidas ;

Vartholomatos, George ;

Hatzimichael, Eleftheria .

INTERNATIONAL JOURNAL OF CANCER, 2011, 129 (04) :773-779

[4] microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer [J].

Braconi, C. ;

Kogure, T. ;

Valeri, N. ;

Huang, N. ;

Nuovo, G. ;

Costinean, S. ;

Negrini, M. ;

Miotto, E. ;

Croce, C. M. ;

Patel, T. .

ONCOGENE, 2011, 30 (47) :4750-4756

[5] Epidermal growth factor receptor expression and gene copy number in conventional hepatocellular carcinoma [J].

Buckley, Anne F. ;

Burgart, Lawrence J. ;

Sahai, Vaibhav ;

Kakar, Sanjay .

AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2008, 129 (02) :245-251

[6] Thermal Stability of RNA Phage Virus-Like Particles Displaying Foreign Peptides [J].

Caldeira, Jerri C. ;

Peabody, David S. .

JOURNAL OF NANOBIOTECHNOLOGY, 2011, 9

[7] GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation [J].

Cheng, Liang ;

Huang, Fa-Zhen ;

Cheng, Li-Fang ;

Zhu, Ya-Qin ;

Hu, Qing ;

Li, Ling ;

Wei, Lin ;

Chen, Da-Wei .

INTERNATIONAL JOURNAL OF NANOMEDICINE, 2014, 9 :921-935

[8] Long noncoding RNA hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways [J].

Fu, Wei-ming ;

Lu, Ying-fei ;

Hu, Bao-guang ;

Liang, Wei-cheng ;

Zhu, Xiao ;

Yang, Hai-di ;

Li, Gang ;

Zhang, Jin-fang .

ONCOTARGET, 2016, 7 (04) :4712-4723

[9] Inhibitory effects of long noncoding RNA MEG3 on hepatic stellate cells activation and liver fibrogenesis [J].

He, Yong ;

Wu, Yu-ting ;

Huang, Cheng ;

Meng, Xiao-Ming ;

Ma, Tao-tao ;

Wu, Bao-Ming ;

Xu, Feng-yun ;

Zhang, Lei ;

Lv, Xiong-Wen ;

Li, Jun .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2014, 1842 (11) :2204-2215

[10] Long noncoding RNAs: Novel insights into hepatocelluar carcinoma [J].