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.