The molecular mechanism of network regulation in the occurrence and development of colorectal cancer (CRC) has been constantly improved. Here, we investigated the biological effects of TEAD4-MAD2L1 axis on proliferation and metastasis of human CRC cells. This study revealed that the expressions of MAD2L1 and TEAD4 in CRC tissues and CRC cell lines were significantly higher than those in adjacent epithelial tissues and normal intestinal epithelial cell line NCM460, and their expressions were significantly positively correlated; Moreover, inhibiting the expression of MAD2L1 or TEAD4 can inhibit the proliferation and migration of CRC cells and promote apoptosis. In addition, the promoter region of MAD2L1 gene has a TEAD4 binding site (motif sequence), and the transcription of MAD2L1 is positively regulated by TEAD4 protein; The inhibition of promotion/migration and promotion of apoptosis of CRC cells by silencing TEAD4 can be saved by the high expression of MAD2L1. In conclusion, our study suggests that the transcription and expression of MAD2L1 is regulated by TEAD4, which further promotes the proliferation and migration of CRC cells in vitro and in vivo, and inhibits apoptosis. MAD2L1 and TEAD4 are potential biomarkers for colorectal cancer.
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We thank the Key Laboratory of environment and genes related to diseases (Xi’an Jiaotong University) and the biomedical experimental center of Xi’an Jiaotong University for providing experimental sites and equipment. We also thank Mr. Xiaofei Wang from the large instrument-sharing center of Xi’an Jiaotong University for his help in flow analysis.
This work was financially supported by the Provincial Health Research Foundation in Shaanxi Province (2022E008), Projects of Xi’an Youth Talent Lift Program (095920221363), National Natural Science Foundation of China (81874192), the Natural Science Basic Research Plan in Shaanxi Province (2022JQ-980), the Key of Research and Development Plan in Shaanxi Province (2021SF-129).
The authors declare no competing interests.
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Li, Q., Tong, D., Jing, X. et al. MAD2L1 is transcriptionally regulated by TEAD4 and promotes cell proliferation and migration in colorectal cancer. Cancer Gene Ther (2023). https://doi.org/10.1038/s41417-022-00586-8