Members of the E26 transformation-specific (ETS) variant transcription factor family act as either tumor suppressors or oncogenic factors in numerous types of cancer. ETS variant transcription factor 7 (ETV7) participates in the development of malignant tumors, whereas its involvement in colorectal cancer (CRC) is less clear. In this study, The Cancer Genome Atlas (TCGA) and immunochemistry staining were applied to check the clinical relevance of ETV7 and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in CRC patients. Overexpression and knockdown of ETV7 and IFIT3 were conducted by transfecting the cells with pCDNA3.1 plasmids and siRNAs, respectively. Western blotting was used to detect the protein expression of ETV7 in CRC cells. Cell Counting Kit-8, cell colony formation, and Transwell assays, as well as flow cytometry, were used to evaluate the proliferation, migration, cell cycle, and apoptosis of CRC cells. Furthermore, western blotting, RT-qPCR, and luciferase assay were used to explore the regulation of ETV7 on IFIT3. Rescue assay was used to investigate the significance of ETV7/IFIT3 axis on CRC progression. We found that ETV7 was upregulated in CRC tissues and cells. Overexpression of ETV7 stimulated the proliferation, migration, and cell cycle amplification, and reduced the apoptosis of CRC cells. Downregulation of ETV7 exerted the opposite effect on CRC cell progression. Moreover, we demonstrated that ETV7 stimulated the transcription activity, the mRNA and protein expression of IFIT3 in CRC cells. There was a positive correlation between ETV7 and IFIT3 in CRC patients. IFIT3 knockdown reversed the promotive effect exerted by overexpression of ETV7 on the amplification and migration of CRC cells. By contrast, overexpression of IFIT3 blocked the inhibitory effect of ETV7-targeting siRNA. In summary, ETV7 induces progression of CRC by activating the transcriptional expression of IFIT3. The EVT7/IFIT3 axis may be a novel target for CRC therapy.

E26 转化特异性 (ETS) 变异转录因子家族的成员在多种癌症中充当肿瘤抑制因子或致癌因子。ETS 变异转录因子 7 (ETV7) 参与恶性肿瘤的发展，但其与结直肠癌 (CRC) 的关系尚不清楚。在本研究中，应用癌症基因组图谱 (TCGA) 和免疫化学染色来检查 CRC 患者中 ETV7 和干扰素诱导的四肽重复蛋白 3 (IFIT3) 的临床相关性。通过分别用pCDNA3.1质粒和siRNA转染细胞来进行ETV7和IFIT3的过表达和敲低。Western blotting检测CRC细胞中ETV7蛋白的表达。使用 Cell Counting Kit-8、细胞集落形成、Transwell 实验以及流式细胞术评估 CRC 细胞的增殖、迁移、细胞周期和凋亡。此外，还利用蛋白质印迹、RT-qPCR和荧​​光素酶测定来探索ETV7对IFIT3的调控。救援试验用于研究 ETV7/IFIT3 轴对 CRC 进展的意义。我们发现 ETV7 在 CRC 组织和细胞中表达上调。ETV7的过度表达刺激了CRC细胞的增殖、迁移和细胞周期放大，并减少了细胞凋亡。ETV7 的下调对 CRC 细胞进展产生相反的影响。此外，我们证明 ETV7 刺激 CRC 细胞中 IFIT3 的转录活性、mRNA 和蛋白表达。CRC患者中ETV7和IFIT3呈正相关。IFIT3敲低逆转了ETV7过表达对CRC细胞扩增和迁移的促进作用。相比之下，IFIT3 的过度表达会阻断 ETV7 靶向 siRNA 的抑制作用。总之，ETV7 通过激活 IFIT3 的转录表达来诱导 CRC 的进展。EVT7/IFIT3 轴可能是 CRC 治疗的新靶点。