Identification of Tumor-Suppressive Controlled Genes: as a Therapeutic Target in Breast Cancer.

Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the family members, (the passenger strand derived from pre-) was significantly downregulated in breast cancer (BC) clinical specimens, and its low expression predicted worse prognoses. Ectopic expression assays showed that transfected cancer cells (MDA-MB-157 and MDA-MB-231) had their aggressive phenotypes significantly suppressed, e.g., their proliferation, migration, and invasion abilities. These data indicated that acted as a tumor-suppressive miRNA in BC cells. Our subsequent search for controlled molecular networks in BC cells yielded a total of 189 genes. Notably, among those 189 genes, cell-cycle-related genes (, , , , , , , , , , , , , , , , and ) were enriched according to a GeneCodis 4 database analysis. Moreover, the overexpression of four genes (, , , and ) significantly predicted worse prognoses for patients with BC according to TCGA analyses. Finally, our assays demonstrated that the overexpression of had cancer-promoting functions in BC cells. The involvement of (the passenger strand) in BC molecular pathogenesis is a new concept in cancer research, and the outcomes of our study strongly indicate the importance of analyzing passenger strands of miRNAs in BC cells.