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.

在缺乏已知的病毒编码癌基因的情况下，小鼠乳腺肿瘤病毒（MMTV）会在小鼠中诱发乳腺癌。MMTV的肿瘤发生被认为主要是通过插入诱变发生的，从而导致细胞原癌基因的活化和所选细胞的生长。在这里，我们调查了MMTV是否编码microRNA（miRNA）和/或调节可能有助于肿瘤发生的宿主miRNA。对MMTV感染的细胞和MMTV诱导的乳腺肿瘤的高通量小RNA测序分析表明，MMTV不编码miRNA。但是，受感染的组织已改变了几种宿主miRNA的水平，包括致癌miRNA簇miR-17-92成员的表达增加。值得注意的是，先前已在人类乳腺癌中报道了miRNA水平的类似变化。结合起来