RNAi Screening Identifies that TEX10 Promotes the Proliferation of Colorectal Cancer Cells by Increasing NF-κB Activation

Colorectal cancer (CRC) has become a predominant cancer worldwide. In order to understand the process of carcinogenesis, an shRNA library screening is employed for searching candidate genes that promote proliferation in the CRC cell line HT29. The candidate genes overlapped with differentially expressed genes in 32 CRC tumor tissues in the GEO dataset GSE8671. The seventh-ranked TEX10 is upregulated in CRC and its knockdown decreased cell proliferation. The TEX10 high-expression group exhibits worse overall survival (P = 0.003) and progression-free survival (P < 0.001) than the TEX10 low-expression group. TEX10 depletion decreases the growth of CRC cells in vitro and in vivo. GSEA indicates that the NF-κB pathway is significantly enriched in the genes downregulated by TEX10 knockdown. Mechanistically, TEX10 interacts with p65 and increases its nuclear localization. TEX10 promotes p65 occupancy at gene promoters and regulates the expression of a subset of p65-targeted genes including TNFAIP8, SAT1 and IL6ST. Taken together, this study identifies that TEX10 promotes the proliferation of CRC cells in a p65-dependent manner. In addition, high TEX10 expression is associated with poor prognosis in CRC patients. TEX10 or p65 were knocked down in HCT116 cells, and the differences in gene expression were compared with shNC, respectively, using RNAseq.