RNAi Screening Identifies that TEX10 Promotes the Proliferation of Colorectal Cancer Cells by Increasing NF‐κB Activation,Advanced Science

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RNAi Screening Identifies that TEX10 Promotes the Proliferation of Colorectal Cancer Cells by Increasing NF‐κB Activation
Advanced Science ( IF 14.3 ) Pub Date : 2020-07-07 , DOI: 10.1002/advs.202000593
Ziyang Wang ₁ , Chunjie Sheng ₁ , Guangyan Kan ₁ , Chen Yao ₁ , Rong Geng ₁ , Shuai Chen ₁

Affiliation

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.

中文翻译：

RNAi 筛选发现 TEX10 通过增加 NF-κB 激活促进结直肠癌细胞增殖

结直肠癌（CRC）已成为世界范围内的主要癌症。为了了解致癌过程，采用短发夹RNA文库筛选来寻找促进CRC细胞系HT29增殖的候选基因。候选基因与GEO数据集GSE8671中32个CRC肿瘤组织中的差异表达基因重叠。排名第七的睾丸表达 10 (TEX10) 在 CRC 中表达上调，其敲低会降低细胞增殖。 TEX10 高表达组的总生存期 ( P = 0.003) 和无进展生存期 ( P = 0.001) 比 TEX10 低表达组更差。 TEX10 耗尽会降低体外和体内 CRC 细胞的生长。基因集富集分析表明，核因子-kappa B 通路在 TEX10 敲除下调的基因中显着富集。从机制上讲，TEX10 与 RELA 相互作用并增加其核定位。 TEX10 促进 RELA 在基因启动子处的占据，并调节 RELA 靶向基因子集的表达，包括TNFAIP8 、 SAT1和IL6ST 。综上所述，本研究确定 TEX10 以 RELA 依赖性方式促进 CRC 细胞的增殖。此外，TEX10 高表达与 CRC 患者预后不良相关。

更新日期：2020-09-10

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