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

• Published in: Virology (New York, N.Y.) N.Y.), 2018-01, Vol.513, p.180-187
• Main Authors: Kincaid, Rodney P., Panicker, Neena G., Lozano, Mary M., Sullivan, Christopher S., Dudley, Jaquelin P., Mustafa, Farah
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Gene Expression Regulation; High-Throughput Nucleotide Sequencing; Host-Pathogen Interactions; Mammary Neoplasms, Experimental - virology; Mammary Tumor Virus, Mouse - physiology; Mice; microRNAs (miRNAs); MicroRNAs - analysis; miR-17–92 cluster; Mouse mammary tumor virus (MMTV); Retroviruses; Virus-host interactions
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2017.09.030

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. [Display omitted] •The MMTV genome does not encode viral miRNAs.•MMTV infection alters host miRNA levels, including the oncogenic miR-17–92 cluster.•Host miRNA changes following MMTV infection occur prior to tumor formation.•MMTV-induced changes to host miRNAs may help drive tumor initiation/maintenance.