波形蛋白
癌症研究
生物
染色质免疫沉淀
电泳迁移率测定
转移
细胞生长
分子生物学
细胞迁移
转录因子
细胞培养
发起人
癌症
基因表达
基因
免疫组织化学
免疫学
遗传学
作者
Qin Wang,Guangwei Zhu,Chunlin Lin,Penghang Lin,Hui Chen,Ruofan He,Yongjian Huang,Shugang Yang,Jianxin Ye
摘要
Abstract Uncontrolled recurrence and metastasis are important reasons for the high mortality rate of malignant tumors. Vimentin is positively correlated with the degree of malignancy of cancer cells. Vimentin is also highly expressed in colorectal cancer (CRC) cells and plays a critical role in the metastasis and prognosis of CRC. However, the molecular mechanism of vimentin in the progression of CRC is incompletely understood. Therefore, the most active regions (nucleotides: 785–1085 nt) of the vimentin promoter in CRC were identified using luciferase experiments. By transcription factor sequence search and mutation analysis, the activator protein 1 (AP‐1) binding site in the region of 785–1085 nt was confirmed. The vimentin promoter activity was enhanced by overexpression of AP‐1. The electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed that the binding site was recognized by AP‐1. By cell proliferation assay, colony‐forming assay, scratch‐wound assay, cell migration assay, and cell invasion assay, we demonstrated that the AP‐1 overexpression increased CRC cell proliferation, migration, and invasion. However, when vimentin was knocked down by vimentin small hairpin RNA in the CRC cell of AP‐1 overexpression, this trend disappeared. Animal experiments and immunohistochemistry showed that AP‐1 promoted tumor growth by regulating the vimentin gene. In summary, AP‐1 affected metastasis, invasion of CRC cells in vitro, and tumor growth in vivo by activating the vimentin promoter. This study might provide new insights into the molecular mechanisms of the development of CRC and provide potential therapeutic targets for CRC.
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