RNA sequencing of Rnaseh2c knockdown Mvt1 mammary cancer cells

To better understand the etiology of metastatic disease, we investigated the impact of genetic polymorphism on metastatic progression. Using RNAseq and exome data analysis, we identified Rnaseh2c, a scaffolding protein of the heterotrimeric RNase H2 endoribonuclease complex, as a novel metastasis susceptibility factor. Mechanistic studies demonstrated that the role of Rnaseh2c in metastatic disease is independent of RNase H2 enzymatic activity and it functions through engagement of the T cell-mediated adaptive immune response. Overall design: Mvt1 mouse mammary carcinoma cells with an shRNA-mediated knockdown of Rnaseh2c were generated along with Mvt1 cells expressing a scramble control shRNA. Cell lines or primary mammary tumors generated from syngeneic orthotopic implantations of the control and knockdown cells were anlayzed. mRNA seq samples included RNA from 3 tumors, 1 from each of 3 experiments, for both scramble and knockdown (sh4). Total RNA seq samples included RNA from 3 biological replicates of cultured control or knockdown Mvt1 cells. Exome seq samples included DNA from 4 pulmonary metastases from 3 mice each scramble and knockdown.