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GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor‐suppressor gene TGFβR2 in colorectal cancer

机译:7号染色体上的GTF2IRD1是一种新的致癌基因可调节结直肠癌中的肿瘤抑制基因TGFβR2

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摘要

Chromosome 7q (Ch.7q) is clonally amplified in colorectal cancer (CRC). We aimed to identify oncogenes on Ch.7q that are overexpressed through DNA copy number amplification and determine the biological and clinical significance of these oncogenes in CRC. We identified general transcription factor 2I repeat domain‐containing protein 1 ( ) as a potential oncogene using a CRC dataset from The Cancer Genome Atlas with a bioinformatics approach. We measured the expression of in 98 patients with CRC using immunohistochemistry and RT‐quantitative PCR (RT‐qPCR). The biological effects of expression were explored by gene set enrichment analysis (GSEA). Next, we undertook in vitro cell proliferation and cell cycle assays using si ‐transfected CRC cells. We further investigated the oncogenic mechanisms through which promoted CRC progression. Finally, we assessed the clinical significance of expression by RT‐qPCR. was overexpressed in tumor cells and liver metastatic lesions. The GSEA revealed a positive correlation between expression and cell cycle progression‐related genes. knockdown inhibited cell proliferation and induced cell cycle arrest in ‐mutated CRC. downregulated the expression of the gene encoding transforming growth factor β receptor 2 ( ), a tumor‐suppressor gene in ‐mutated CRC. On multivariate analysis, high expression was an independent poor prognostic factor. Clinicopathological analysis showed that expression was positively correlated with liver metastasis. In conclusion, promoted CRC progression by downregulating and could be a prognostic biomarker on Ch.7q in CRC. could also be a novel oncogene in CRC.
机译:染色体7q(Ch.7q)在结直肠癌(CRC)中被克隆扩增。我们旨在鉴定通过DNA拷贝数扩增而过表达的Ch.7q癌基因,并确定这些癌基因在CRC中的生物学和临床意义。我们使用The Cancer Genome Atlas的CRC数据集和生物信息学方法,将通用转录因子2I重复结构域含蛋白1()鉴定为潜在的癌基因。我们使用免疫组织化学和RT定量PCR(RT-qPCR)测量了98例CRC患者的表达。通过基因组富集分析(GSEA)探索了表达的生物学效应。接下来,我们使用si转染的CRC细胞进行了体外细胞增殖和细胞周期测定。我们进一步研究了促进CRC进展的致癌机制。最后,我们通过RT-qPCR评估了表达的临床意义。在肿瘤细胞和肝转移病灶中过表达。 GSEA揭示了表达与细胞周期进展相关基因之间呈正相关。组合式抑制突变的CRC细胞增殖和诱导细胞周期停滞。下调了CRC编码的肿瘤抑制基因转化生长因子β受体2()的基因表达。在多变量分析中,高表达是独立的不良预后因素。临床病理分析表明,表达与肝转移呈正相关。总之,通过下调促进了CRC进展,并且可能是CRC Ch.7q的预后生物标志物。也可能是CRC中的新型致癌基因。

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