SLC34A2 promotes cancer proliferation and cell cycle progression by targeting TMPRSS3 in colorectal cancer

Abstract

Solute carrier family 34 member 2 (SLC34A2), a family member of sodium-driven phosphate cotransporters, has been reported to facilitate cell proliferation and tumor growth. However, the functional mechanism by which SLC34A2 promotes cell growth and cell cycle progression remains poorly understood. Here, we reported that SLC34A2 was overexpressed in CRC by analysis of TCGA and GEO datasets. A total of 45 differentially expressed genes (DEGs) were identified from comparing SLC34A2-high or –low groups and functional enrichment analysis of these DEGs demonstrated that cell cycle pathway was enriched. Interestingly, we found a positive correlation between TMPRSS3 (transmembrane serine protease 3) and SLC34A2, which was confirmed by RT-qPCR and western blotting. Furthermore, TMPRSS3 was also upregulated in CRC tumor tissues compared to normal tissues. Patients with high TMPRSS3 expression had poor prognosis. Functionally, TMPRSS3 deficiency inhibited cell proliferation and colony formation in CRC cells. TMPRSS3 overexpression in SLC34A2-deficient cells antagonized siSLC34A2-mediated cell cycle inhibition by promoting cyclin E, cyclin A protein expression. Based on these results, our study suggests that SLC34A2 promotes cancer proliferation and cell cycle progression by targeting TMPRSS3 in colorectal cancer cells.