De novo assembly and transcriptome characterization: Novel insights into the mechanisms of primary ovarian cancer in Microtus fortis

The natural incidence of primary epithelial ovarian cancer (OVC) in adult female voles of some established strains of Microtus fortis is relatively high. M. fortis OVC has some pathological similarities to human epithelial OVC, therefore M. fortis represents the latest and most valuable animal model for studying human OVC. The lack of available genetic information for M. fortis limits the use of common immunological methods; thus, high-throughput sequencing technologies have been used to reveal the mechanisms of primary OVC in M. fortis. The individuals with cancer were diagnosed using histopathologic hematoxylin and eosin staining. The present study used RNA-sequencing (RNA-seq) technology to establish a de novo assembly of the M. fortis transcriptome produced 339,830 unigenes by the short reads assembly program Trinity. Comparisons were made between OVC and healthy ovarian tissue (OV) and between fallopian tube cancer (FTC) and healthy fallopian tube (FT) tissues using RNA-seq analysis. A total of 3,434 differentially expressed genes (DEGs) were identified in OVC tissue compared with OV tissue using RNA-Seq by Expectation-Maximization software, including 1,950 significantly upregulated and 1,484 significantly downregulated genes. There were 2,817 DEGs identified in the FTC tissues compared with the FT tissue, including 1,762 significantly upregulated and 1,055 significantly downregulated genes. Pathway enrichment analysis revealed that upregulated transcripts in the OVC vs. OV groups were involved in cell growth and proliferation-associated pathways, whereas the downregulated DEGS in the OVC vs. OV groups were enriched in steroid biosynthesis-related pathways. Furthermore, the tumor suppressor gene, p53, was downregulated in the FTC and OVC compared with the FT and OV groups, respectively; whereas, genes that promoted cell migration, such as Ras-related protein Rap-1b, Ras homolog family member A and RAC1, were upregulated. In summary, to the best of our knowledge, the present study characterized the M. fortis de novo transcriptome of OV and FT tissues and to perform RNA-seq quantification to analyze the differences in healthy and cancerous OV and FT tissues. These results identified pathways that differed between cancerous and healthy M. fortis tissues. Analysis of these pathways may help to reveal the pathogenesis of primary OVC in M. fortis in future work.