Department of Gastroenterology, Shanxi Academy of Medical Science, Shanxi Bethune Hospital, Taiyuan, China.
Department of Surgery, Shanxi Academy of Medical Science, Shanxi Bethune Hospital, Taiyuan, China.
Funct Integr Genomics. 2024 Jan 10;24(1):8. doi: 10.1007/s10142-023-01282-y.
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）变体转录因子家族的成员在多种类型的癌症中既可以作为肿瘤抑制因子，也可以作为致癌因子。ETS 变体转录因子 7（ETV7）参与恶性肿瘤的发生，但其在结直肠癌（CRC）中的作用尚不清楚。本研究应用癌症基因组图谱（TCGA）和免疫化学染色技术检测 ETV7 和干扰素诱导的四肽重复蛋白 3（IFIT3）在 CRC 患者中的临床相关性。通过转染 pCDNA3.1 质粒和 siRNA 分别过表达和敲低 ETV7 和 IFIT3。Western blot 检测 CRC 细胞中 ETV7 的蛋白表达。细胞计数试剂盒-8、细胞集落形成和 Transwell 检测以及流式细胞术用于评估 CRC 细胞的增殖、迁移、细胞周期和凋亡。此外，Western blot、RT-qPCR 和荧光素酶测定用于探讨 ETV7 对 IFIT3 的调控作用。挽救实验用于研究 ETV7/IFIT3 轴对 CRC 进展的意义。我们发现 ETV7 在 CRC 组织和细胞中上调。过表达 ETV7 刺激 CRC 细胞的增殖、迁移和细胞周期扩增，并减少细胞凋亡。下调 ETV7 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 与 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。相反，IFIT3 的过表达阻断了 ETV7 靶向 siRNA 的抑制作用。总之，ETV7 通过激活 IFIT3 的转录表达诱导 CRC 的进展。EVT7/IFIT3 轴可能是 CRC 治疗的新靶点。
