Identification of the novel therapeutic target gene SLC12A9, which determines the prognosis of patients with colorectal cancer.

BACKGROUND: Feasible therapeutic targets need to be identified to overcome tumor heterogeneity and ameliorate therapeutic resistance. We explored the identification of oncogenes on Ch.7q, which is amplified ubiquitously in colorectal cancer (CRC). In this study, we focused on SLC12A9, which encodes a channel protein that regulates ion concentration inside and outside of the cell. MATERIALS AND METHODS: Expression and survival analyses of SLC12A9 were performed using reverse transcription quantitative polymerase chain reaction, The Cancer Genome Atlas dataset, and immunohistochemistry. A gene set enrichment analysis (GSEA) was performed to elucidate the correlation between SLC12A9 and gene sets associated with tumor progression. Subsequently, an in vitro proliferation assay was performed using SLC12A9-knockdown CRC cells. RESULTS: SLC12A9 was highly expressed in tumor cells, and its high expression was associated with a poor prognosis. The GSEA revealed an association with mTORC1 signaling. In the colony formation assay, SLC12A9 knockdown by siRNA suppressed the proliferative capacity of CRC cells. Public single-cell RNA sequencing data have revealed that SLC12A9 is derived from malignant epithelial cells in CRC tissues. CONCLUSION: Our results suggest that abundant SLC12A9 expression is associated with a poor prognosis due to the devastating growth of CRC cells, in part via the mTORC1 signaling pathway.