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Published on: January 19, 2015
A host non-coding RNA, nc886, plays a pro-viral role by promoting virus trafficking to the nucleus
Enkhjin Saruuldalai1, Jiyoung Park2, Dongmin Kang2
1Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Korea.
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.
Insights
Human nc886 RNA enhances adenovirus replication by aiding nuclear entry, independent of PKR inhibition. This finding could improve oncolytic virotherapy and create better animal models.
Area of Science:
- Virology
- Molecular Biology
- Cancer Research
Background:
- Understanding virus-host interactions is key for therapeutic applications.
- Oncolytic virotherapy using adenovirus shows promise but faces limitations in efficacy and preclinical modeling.
- Human non-coding RNA nc886 inhibits Protein Kinase R (PKR), an antiviral protein.
Purpose of the Study:
- To investigate the role of nc886 in adenoviral gene expression and replication.
- To elucidate the mechanism by which nc886 affects adenovirus.
- To explore the potential of nc886 in improving oncolytic virotherapy and animal models.
Main Methods:
- Studied the effect of nc886 on adenoviral gene expression and replication.
- Investigated the mechanism of nc886's action, including its effect on PKR and nuclear entry.
- Examined nc886's role in xenogeneic mouse models.
Main Results:
- nc886 significantly promotes adenoviral gene expression and replication.
- The pro-adenoviral effect of nc886 is independent of its PKR inhibitory function.
- nc886 facilitates adenovirus nuclear entry by modulating the kinesin pathway.
- nc886 promotes adenovirus replication in mouse cells when expressed xenogeneically.
Conclusions:
- Discovered a novel mechanism where host ncRNA nc886 promotes adenovirus replication via the kinesin pathway.
- nc886 expression levels may impact oncolytic virotherapy efficacy in certain cancers.
- nc886 offers potential for enhancing oncolytic adenovirus efficacy and developing improved preclinical models.
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