Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer

Abstract

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.

Microenvironment of metastasis reveals key predictors of PD-1 blockade response in renal cell carcinoma

“…CXCR6 is a chemokine receptor overexpressed in tumor-infiltrating lymphocytes involved in the recruitment of T cells into RCC tissue ( 70 ). The Basic Transcription Factor 3 ( BTF3 ) is required for the transcriptional initiation and known to be an oncogene in colorectal cancer ( 71 ). Furthermore, it is overexpressed in pancreatic ductal carcinoma cells ( 72 ) and in prostate cancer where it sustains a cancer stem-like phenotype ( 73, 74 ).…”

“…CXCR6 is a chemokine receptor overexpressed in tumourinfiltrating lymphocytes involved in the recruitment of T cells into RCC tissue (Oldham et al, 2012). The Basic Transcription Factor 3 (BTF3) is required for the transcriptional initiation and known to be an oncogene in colorectal cancer (Wang et al, 2021), overexpressed in pancreatic ductal carcinoma cells (Kusumawidjaja et al, 2007) and in prostate cancer where it sustains cancer stem-like phenotype (Symes et al, 2013. To further assess the clinical relevance of the TID score and the associated genes, we compared them to existing transcriptomic scores previously published to predict patient clinical response to ICB therapy.…”

Combining Recombinase-Mediated Cassette Exchange Strategy with Quantitative Proteomic and Phosphoproteomic Analyses to Inspect Intracellular Functions of the Tumor Suppressor Galectin-4 in Colorectal Cancer Cells

“…In CRC tissue, BTF3 is overexpressed and correlates with a poor prognosis [ 27 ]. A recent study indicates that the oncogenic action in colon cancer is linked to an induction of a DNA helicase (CHD1L) and inhibition of E3 ubiquitin ligase HERC2-mediated p53 degradation [ 28 ]. BCAR1 belongs to the family of CAS proteins, which are overexpressed in many solid tumors, where they promote invasion and metastasis [ 29 , 30 ].…”