Department of General Surgery, People's Hospital of Hunan Province, First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, China.
Cell Death Dis. 2019 Jul 1;10(7):509. doi: 10.1038/s41419-019-1747-2.
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.
基本转录因子 3 (BTF3) 与多种癌症的发生有关。本研究旨在阐明 BTF3 在结直肠癌 (CRC) 组织中的作用。我们从 2011 年 11 月至 2016 年 12 月在我院接受手术的 90 例患者中获得了 CRC 组织或其配对的相邻非癌组织 (ANCT),然后进行基因微阵列检测以检测基因表达的显著变化,并通过免疫组织化学和实时 PCR 确认组织中的表达。我们转染或注射沉默 BTF3 (BTF3-siRNA) 质粒到细胞和裸鼠中,并用流式细胞术测量 CRC 细胞的致瘤性,并研究 CRC 细胞中 BTF3 下游基因 (MAD2L2、MCM3 和 PLK1) 的表达水平。BTF3 表达水平在 CRC 组织中不仅明显高于 ANCT 组织 (2.61±0.07 比 1.90±0.03,P<0.001),而且 BTF3-siRNA 还降低了裸鼠模型中的肿瘤形成。此外,根据基因微阵列分析的数据,检测到 MAD2L2、MCM3 和 PLK1 是 BTF3 的下游靶基因,它们的表达与 BTF3 表达呈正相关。同样,通过将 BTF3-siRNA 转染到 HCT116 细胞中,我们发现 BTF3-siRNA 可以降低细胞活力并诱导细胞凋亡和阻断细胞周期。总之,BTF3 与 CRC 呈正相关,BTF3-siRNA 通过降低 MAD2L2、MCM3 和 PLK1 的活性来减弱结直肠癌细胞的致瘤性。