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.
Highlights
One of the most predominant malignancies in China is colorectal cancer (CRC) whose incidence in the Chinese population continues to grow[1]
Basic transcription factor 3 (BTF3) protein expression levels in 90 colorectal cancer patients were evaluated using IHC which clearly indicated a significantly different expression of BTF3 detected in tissue samples from ANCT (n = 90) and CRC (n = 90)
These CRC tissues from the patients whose pathological characteristics showed that TNM (I + II) staging accounted for 58.9, 63.3% were in N0 of lymph node metastasis and M0 of distant metastasis, 86.7% patients were belonging to pathological class I + II, and there was a significant difference of BTF3 expression in different TNM staging between CRC and ANCT (Fig. 2a and Table 1)
Summary
One of the most predominant malignancies in China is colorectal cancer (CRC) whose incidence in the Chinese population continues to grow[1]. It is likely that the development of sophisticated screening techniques to detect CRC at a very early stage will greatly change the mortality rate[2,3]. It has been demonstrated that BTF3b lacks the first 44 residues present in BTF3a It cannot initiate transcription even though it readily binds to RNA polymerase II7. Increasing evidence has shown that, as a transcription factor, BTF3 is associated with the development of several types of cancers. BTF3 has been shown to be involved in the stimulation of proliferation of cells, reducing of cell cycle regulation and gastric cancer cell apoptosis[8]. Overexpression of BTF3 in pancreatic cancer cells[10], where it functions to regulate transcription per se as opposed to direct modulation of apoptosis through actions on genes associated with cancer including ABL2, ATM, EPHB2 and HPSE2. The underlying mechanisms through which BTF3 regulates the development of CRC have not been fully elucidated
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