@article{ed5d8fad1a6946a48dc678a0e31226e6,
title = "A host non-coding RNA, nc886, plays a pro-viral role by promoting virus trafficking to the nucleus",
abstract = "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.",
keywords = "Protein Kinase R, adenovirus, host tropism, kinesin, nc886, non-coding RNA, oncolytic virotherapy",
author = "Enkhjin Saruuldalai and Jiyoung Park and Dongmin Kang and Shin, {Seung Phil} and Im, {Wonkyun Ronny} and Lee, {Hwi Ho} and Jang, {Jiyoung Joan} and Park, {Jong Lyul} and Kim, {Seon Young} and Hwang, {Jung Ah} and Kim, {Young Dong} and Lee, {Jung Hoon} and Park, {Eun Jung} and Lee, {Yeon Su} and Kim, {In Hoo} and Lee, {Sang Jin} and Lee, {Yong Sun}",
note = "Funding Information: We thank Dr. Harald Wodrich (Universit{\'e} de Bordeaux, France) for an antibody against AdV protein VII. The illustration ( Figure 7 ) was supported by Suhyun Chae from National Cancer Center Korea. This work was supported by grants from the National Research Foundation of Korea funded by the Korea government ( Ministry of Science and ICT ; MSIT) ( NRF-2019R1A2C2088108 to Y.S.L.); the National Cancer Center , Korea ( NCC-2110191 to Y.S.L. and NCC-2110192 to I.-H.K.); the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation funded by the Ministry of Science and ICT (MSIT) ( NRF-2017M3C9A6044517 to Y.-S.L.); International Cooperation & Education Program of National Cancer Center ( NCCRI·NCCI 52210-52211 , 2021 to E.S.); and the Korea Basic Science Institute (National Research Facilities and Equipment Center) funded by the Ministry of Education ( 2019R1A6C1010020 to D.K.). Funding Information: We thank Dr. Harald Wodrich (Universit{\'e} de Bordeaux, France) for an antibody against AdV protein VII. The illustration (Figure 7) was supported by Suhyun Chae from National Cancer Center Korea. This work was supported by grants from the National Research Foundation of Korea funded by the Korea government (Ministry of Science and ICT; MSIT) (NRF-2019R1A2C2088108 to Y.S.L.); the National Cancer Center, Korea (NCC-2110191 to Y.S.L. and NCC-2110192 to I.-H.K.); the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation funded by the Ministry of Science and ICT (MSIT) (NRF-2017M3C9A6044517 to Y.-S.L.); International Cooperation & Education Program of National Cancer Center (NCCRI·NCCI 52210-52211, 2021 to E.S.); and the Korea Basic Science Institute (National Research Facilities and Equipment Center) funded by the Ministry of Education (2019R1A6C1010020 to D.K.). E.S.: Data curation, Formal Analysis, Funding acquisition, Investigation, Methodology, Writing – review & editing. J.P.: Investigation. D.K.: Data curation, Formal Analysis, Funding acquisition. S.-P.S.: Investigation. W.R.I.: Investigation. H.-H.L.: Investigation. J.J.J.: Investigation, Formal Analysis. J.-L.P.: Formal Analysis. S.-Y.K.: Formal Analysis. J.-A.H.: Methodology. Y.-D.K.: Data curation. J.-H.L.: Data curation. E.J.P.: Supervision. Y.-S.L.: Conceptualization, Funding acquisition, Project administration, Writing – review & editing, Investigation. I.-H.K.: Conceptualization, Funding acquisition, Supervision. S.-J.L.: Conceptualization, Writing – review & editing, Supervision, Investigation. Y.S.L.: Conceptualization, Data curation, Formal Analysis, Funding acquisition, Investigation, Project administration, Supervision, Visualization, Writing – original draft, Writing – review & editing. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = mar,
day = "17",
doi = "10.1016/j.omto.2022.02.018",
language = "English",
volume = "24",
pages = "683--694",
journal = "Molecular Therapy - Oncolytics",
issn = "2372-7705",
publisher = "Cell Press",
}