Open AccessRNAi Screening Identifies that TEX10 Promotes the Proliferation of Colorectal Cancer Cells by Increasing NF‐ κ B Activation
Author(s) -
Wang Ziyang,
Sheng Chunjie,
Kan Guangyan,
Yao Chen,
Geng Rong,
Chen Shuai
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202000593
Subject(s) - gene knockdown , small hairpin rna , rna interference , cancer research , carcinogenesis , cell growth , biology , downregulation and upregulation , cancer , colorectal cancer , gene , gene expression , rna , genetics
Colorectal cancer (CRC) has become a predominant cancer worldwide. To understand the process of carcinogenesis, a short hairpin RNA library screening is employed to search for candidate genes that promote proliferation in the CRC cell line HT29. The candidate genes overlap with differentially expressed genes in 32 CRC tumor tissues in the GEO dataset GSE8671. The seventh‐ranked testis expressed 10 (TEX10) is upregulated in CRC and its knockdown decreases 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. Gene set enrichment analysis indicates that the nuclear factor‐kappa B pathway is significantly enriched in the genes downregulated by TEX10 knockdown. Mechanistically, TEX10 interacts with RELA and increases its nuclear localization. TEX10 promotes RELA occupancy at gene promoters and regulates the expression of a subset of RELA‐targeted genes, including TNFAIP8 , SAT1 , and IL6ST . Taken together, this study identifies that TEX10 promotes the proliferation of CRC cells in an RELA‐dependent manner. In addition, high TEX10 expression is associated with poor prognosis in CRC patients.