A host non-coding RNA, nc886, plays a pro-viral role by promoting virus trafficking to the nucleus

Molecular Therapy: Oncolytics

Seon-Young Kim¹  Young-Dong Kim¹  Yeon-Su Lee²  Wonkyun Ronny Im³  Jiyoung Joan Jang³  Sang-Jin Lee³  Hwi-Ho Lee³  Enkhjin Saruuldalai³  Eun Jung Park⁴  Seung-Phil Shin⁵  Yong Sun Lee⁶  Dongmin Kang⁷  Jiyoung Park⁷  Jung-Hoon Lee⁸  In-Hoo Kim⁹  Jong-Lyul Park^1,10  Jung-Ah Hwang^1,10 

[1] Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea;Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Korea;Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Korea;Department of Life Science, Hallym University, Chuncheon 24252, Korea;Division of Cancer Immunology, Research Institute, National Cancer Center, Goyang 10408, Korea;Division of Clinical Cancer Research, Research Institute, National Cancer Center, Goyang 10408, Korea;Fluorescence Core Imaging Center, Department of Life Science, Ewha Womans University, Seoul 03760, Korea;Genomics Core Facility, Research Core Center, Research Institute, National Cancer Center, Goyang 10408, Korea;Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Korea;Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141, Korea;

关键词: nc886;    adenovirus;    kinesin;    oncolytic virotherapy;    non-coding RNA;    host tropism;   

DOI  :  

来源: DOAJ

【 摘 要 】

Elucidation of the interplay between viruses and host cells is crucial for taming viruses to benefit human health. Cancer therapy using adenovirus, called oncolytic virotherapy, is a promising treatment option but is not robust in all patients. In addition, inefficient replication of human adenovirus in mouse hampered the development of an in vivo model for preclinical evaluation of therapeutically engineered adenovirus. nc886 is a human non-coding RNA that suppresses Protein Kinase R (PKR), an antiviral protein. In this study, we have found that nc886 greatly promotes adenoviral gene expression and replication. Remarkably, the stimulatory effect of nc886 is not dependent on its function to inhibit PKR. Rather, nc886 facilitates the nuclear entry of adenovirus via modulating the kinesin pathway. nc886 is not conserved in mouse and, when xenogeneically expressed in mouse cells, promotes adenovirus replication. Our investigation has discovered a novel mechanism of how a host ncRNA plays a pro-adenoviral role. Given that nc886 expression is silenced in a subset of cancer cells, our study highlights that oncolytic virotherapy might be inefficient in those cells. Furthermore, our findings open future possibilities of harnessing nc886 to improve the efficacy of oncolytic adenovirus and to construct nc886-expressing transgenic mice as an animal model.

【 授权许可】

Unknown