Positive expression of basic transcription factor 3 predicts poor survival of colorectal cancer patients: possible mechanisms involved

Abstract

Basic transcription factor 3 (BTF3) is associated with the development of several cancers. The aim of our study was to elucidate the role of BTF3 in colorectal cancer (CRC) tissues. CRC tissues or their paired adjacent noncancerous (ANCT) tissues were obtained from 90 patients who underwent operations in our hospital from November 2011 to December 2016, and then we implemented a gene microarray assay for detecting significant changes in gene expression and confirmed expression in tissues using immunohistochemistry and real-time PCR. We transfected or injected the silencing BTF3 (BTF3-siRNA) plasmid into cells and nude mice, and measured the tumorigenicity of CRC cells with flow cytometry and studied the expression level of BTF3 downstream genes (MAD2L2, MCM3 and PLK1) in CRC cells. BTF3 expression level was not only significantly higher in CRC tissue than in ANCT tissue (2.61 ± 0.07 vs 1.90 ± 0.03, P < 0.001) but BTF3-siRNA decreased tumor formation in a nude mice model. Furthermore, based on the data of gene microarray analysis, MAD2L2, MCM3 and PLK1 were detected as the downstream target genes of BTF3 and their expressions were positive related with BTF3 expression. Also, through transfecting BTF3-siRNA into HCT116 cells, we found that BTF3-siRNA could decrease cell viability and induced cell apoptosis and blocking the cell cycle. In conclusion, BTF3 is positively related to CRC and BTF3-siRNA attenuated the tumorigenicity of colorectal cancer cells via MAD2L2, MCM3 and PLK1 activity reduction.

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

“…Transcriptional and post-transcriptional gene and pathway dysregulation are important cancer signatures in CRC ( Porcellini et al, 2018 ). BTF3, namely, basic transcription factor 3, has been proven to be an oncogene and hazardous prognosticator in CRC ( Liu et al, 2019b ). As a transcription factor, BTF3 is believed to regulate gene expression by binding target promoters, and this mechanism has been reported in breast cancer ( Porcellini et al, 2018 ).…”

“…Here, we refer to this transcription factor characteristic of BTF3 as the transcriptional mechanism, a molecular function primarily occurring in the nucleus. In CRC, the function of BTF3 was first reported to be linked to MAD2L2, MCM3, and PLK1 ( Liu et al, 2019b ). In addition, the alias name of BTF3 is nascent-polypeptide-associated complex beta (NACB).…”

“…Basic transcription factor 3 (BTF3), also known as nascent-polypeptide-associated complex (NAC) beta (NACB), was reported to serve as an oncogene and convey worse prognosis in gastric cancer ( Liu et al, 2013 ; Zhang et al, 2017 ), pancreatic cancer ( Kusumawidjaja et al, 2007 ), osteosarcoma ( Liu et al, 2019a ), cervical cancer ( Wu et al, 2020 ), hypopharyngeal squamous cell carcinoma ( Zhang et al, 2019 ), prostate cancer ( Hu et al, 2019 ), breast cancer ( Ding et al, 2019 ), and CRC ( Liu et al, 2019b ). BTF3 initiates transcription by binding to promoter elements, such as TATA box and CAAT box sequences, in the promoter region ( Cavallini et al, 1988 ; Kanno et al, 1992 ).…”

“…In our previous study, we reported the oncogenic function of BTF3 in CRC cell lines ( Li et al, 2019 ). According to Liu et al (2019b) , reduced MAD2L2, MCM3, and PLK1 activity may be involved. However, the direct targets of BTF3 as a transcription factor and part of the NAC complex, and the reason for its elevated expression in CRC, remain obscure.…”

Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells

“…The protein is overexpressed in various cancer cell types, including glioma, hepatocarcinoma, pancreatic ductal adenocarcinoma, and colon cancer cells [52]. Recent reports have shown that downregulation of BTF3 attenuates tumorigenesis in colon cancer cells [53,54]. SNAIL1 is a key transcription factor in the early epithelial-to-mesenchymal transition period, the initial and critical timeframe for metastasis [55].…”