MMTV does not encode viral microRNAs but alters the levels of cancer-associated host microRNAs

Rodney P Kincaid; Neena G Panicker; Mary M Lozano; Christopher S Sullivan; Jaquelin P Dudley; Farah Mustafa

doi:10.1016/j.virol.2017.09.030

MMTV does not encode viral microRNAs but alters the levels of cancer-associated host microRNAs

Virology. 2018 Jan 1:513:180-187. doi: 10.1016/j.virol.2017.09.030. Epub 2017 Nov 5.

Authors

Rodney P Kincaid¹, Neena G Panicker², Mary M Lozano³, Christopher S Sullivan⁴, Jaquelin P Dudley⁵, Farah Mustafa⁶

Affiliations

¹ Department of Molecular Biosciences, The University of Texas at Austin, 100 East 24th Street, NHB 2.616, Austin, TX, United States of America. Electronic address: rpkincaid@gmail.com.
² Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Tawam Hospital Complex, P.O. Box 17666, Al Ain, United Arab Emirates. Electronic address: ngpanicker@uaeu.ac.ae.
³ Department of Molecular Biosciences, The University of Texas at Austin, 100 East 24th Street, NHB 2.616, Austin, TX, United States of America. Electronic address: mlozano@austin.utexas.edu.
⁴ Department of Molecular Biosciences, The University of Texas at Austin, 100 East 24th Street, NHB 2.616, Austin, TX, United States of America. Electronic address: chris_sullivan@austin.utexas.edu.
⁵ Department of Molecular Biosciences, The University of Texas at Austin, 100 East 24th Street, NHB 2.616, Austin, TX, United States of America. Electronic address: jdudley@austin.utexas.edu.
⁶ Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Tawam Hospital Complex, P.O. Box 17666, Al Ain, United Arab Emirates. Electronic address: fmustafa@uaeu.ac.ae.

Abstract

Mouse mammary tumor virus (MMTV) induces breast cancer in mice in the absence of known virally-encoded oncogenes. Tumorigenesis by MMTV is thought to occur primarily through insertional mutagenesis, leading to the activation of cellular proto-oncogenes and outgrowth of selected cells. Here we investigated whether MMTV encodes microRNAs (miRNAs) and/or modulates host miRNAs that could contribute to tumorigenesis. High throughput small RNA sequencing analysis of MMTV-infected cells and MMTV-induced mammary tumors demonstrates that MMTV does not encode miRNAs. However, infected tissues have altered levels of several host miRNAs, including increased expression of members of the oncogenic miRNA cluster, miR-17-92. Notably, similar changes in miRNA levels have been previously reported in human breast cancers. Combined, our results demonstrate that virally encoded miRNAs do not contribute to MMTV-mediated tumorigenesis, but that changes in specific host miRNAs in infected cells may contribute to virus replication and tumor biology.

Keywords: Breast cancer; Mouse mammary tumor virus (MMTV); Retroviruses; Virus-host interactions; miR-17–92 cluster; microRNAs (miRNAs).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gene Expression Regulation*
High-Throughput Nucleotide Sequencing
Host-Pathogen Interactions*
Mammary Neoplasms, Experimental / virology*
Mammary Tumor Virus, Mouse / physiology*
Mice
MicroRNAs / analysis*

Substances

MicroRNAs

Grants and funding

R01 CA167053/CA/NCI NIH HHS/United States