MAD2L1 is transcriptionally regulated by TEAD4 and promotes cell proliferation and migration in colorectal cancer
MAD2L1 is transcriptionally regulated by TEAD4 and promotes cell proliferation and migration in colorectal cancer
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MAD2L1 受 TEAD4 转录调控，促进结直肠癌细胞增殖和迁移
DOI：
10.1038/s41417-022-00586-8
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发表时间：
2023-01-04
影响因子：
6.4
通讯作者：
Zhang, Mingxin
中科院分区：
文献类型：
--
作者：
Li, Qian;Tong, Dongdong;Zhang, Mingxin
网络调控在结直肠癌发生发展中的分子机制不断完善。在此，我们研究了TEAD 4-MAD 2L 1轴对人结直肠癌细胞增殖和转移的生物学作用。本研究揭示MAD 2L 1和TEAD 4在结直肠癌组织和结直肠癌细胞系中的表达均显著高于癌旁上皮组织和正常肠上皮细胞系NCM 460，且二者的表达呈显著正相关;抑制MAD 2L 1或TEAD 4的表达可抑制结直肠癌细胞的增殖和迁移，促进细胞凋亡。此外，MAD 2L 1基因的启动子区有一个TEAD 4结合位点（基序序列），MAD 2L 1的转录受TEAD 4蛋白的正调控;沉默TEAD 4抑制CRC细胞的增殖/迁移和促进细胞凋亡，可通过MAD 2L 1的高表达得以挽救。因此，我们的研究表明MAD 2L 1的转录和表达受TEAD 4的调控，从而进一步促进结直肠癌细胞在体内外的增殖和迁移，并抑制细胞凋亡。MAD 2L 1和TEAD 4是结直肠癌的潜在生物标志物。
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.