Wang Hantao, Xing Junjie, Wang Wei, Lv Guifen, He Haiyan, Lu Yeqing, Sun Mei, Chen Haiyan, Li Xu
Department of Colorectal Surgery, Changhai Hospital, Shanghai, China.
Department of Digestive Endoscopy, Changhai Hospital, Shanghai, China.
Front Cell Dev Biol. 2021 Feb 11;8:601502. doi: 10.3389/fcell.2020.601502. eCollection 2020.
Colorectal cancer (CRC) is one of the most commonly diagnosed and leading causes of cancer mortality worldwide, and the prognosis of patients with CRC remains unsatisfactory. Basic transcription factor 3 (BTF3) is an oncogene and hazardous prognosticator in CRC. Although two distinct functional mechanisms of BTF3 in different cancer types have been reported, its role in CRC is still unclear. In this study, we aimed to molecularly characterize the oncogene BTF3 and its targets in CRC. Here, we first identified the transcriptional targets of BTF3 by applying combined RNA-Seq and ChIP-Seq analysis, identifying CHD1L as a transcriptional target of BTF3. Thereafter, we conducted immunoprecipitation (IP)-MS and E3 ubiquitin ligase analysis to identify potential interacting targets of BTF3 as a subunit of the nascent-polypeptide-associated complex (NAC). The analysis revealed that BTF3 might also inhibit E3 ubiquitin ligase HERC2-mediated p53 degradation. Finally, miRNAs targeting BTF3 were predicted and validated. Decreased miR-497-5p expression is responsible for higher levels of BTF3 post-transcriptionally. Collectively, we concluded that BTF3 is an oncogene, and there may exist a transcription factor and NAC-related proteolysis mechanism in CRC. This study provides a comprehensive basis for understanding the oncogenic mechanisms of BTF3 in CRC.
结直肠癌（CRC）是全球最常被诊断出的癌症之一，也是癌症死亡的主要原因，CRC患者的预后仍然不尽人意。基础转录因子3（BTF3）是CRC中的一种癌基因和不良预后指标。尽管已经报道了BTF3在不同癌症类型中的两种不同功能机制，但其在CRC中的作用仍不清楚。在本研究中，我们旨在从分子水平上表征CRC中癌基因BTF3及其靶点。在此，我们首先通过联合RNA测序和染色质免疫沉淀测序（ChIP-Seq）分析确定了BTF3的转录靶点，鉴定出CHD1L是BTF3的转录靶点。此后，我们进行了免疫沉淀（IP）-质谱分析和E3泛素连接酶分析，以确定BTF3作为新生多肽相关复合物（NAC）亚基的潜在相互作用靶点。分析表明，BTF3还可能抑制E3泛素连接酶HERC2介导的p53降解。最后，对靶向BTF3的微小RNA（miRNA）进行了预测和验证。miR-497-5p表达降低是导致转录后BTF3水平升高的原因。总的来说，我们得出结论，BTF3是一种癌基因，并且CRC中可能存在一种转录因子和与NAC相关的蛋白水解机制。本研究为理解BTF3在CRC中的致癌机制提供了全面的基础。
