Vimentin affects colorectal cancer proliferation, invasion, and migration via regulated by activator protein 1.
J Cell Physiol
; 236(11): 7591-7604, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34041752
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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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vimentina
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Neoplasias Colorretais
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Movimento Celular
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Fator de Transcrição AP-1
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Proliferação de Células
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China