<br>波形蛋白通过激活蛋白1的调节影响结直肠癌的增殖、侵袭和迁移,Journal of Cellular Physiology

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波形蛋白通过激活蛋白1的调节影响结直肠癌的增殖、侵袭和迁移
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-05-27 , DOI: 10.1002/jcp.30402
Qin Wang _{1,

2} , Guangwei Zhu _{1,

2} , Chunlin Lin _{1,

2} , Penghang Lin _{1,

2} , Hui Chen _{1,

2} , Ruofan He _{1,

2} , Yongjian Huang ₁ , Shugang Yang ₁ , Jianxin Ye _{1,

2}

Affiliation

不受控制的复发和转移是恶性肿瘤死亡率高的重要原因。 Vimentin与癌细胞的恶性程度呈正相关。波形蛋白在结直肠癌（CRC）细胞中也高表达，在结直肠癌的转移和预后中发挥着关键作用。然而，波形蛋白在结直肠癌进展中的分子机制尚不完全清楚。因此，使用荧光素酶实验鉴定了 CRC 中波形蛋白启动子最活跃的区域（核苷酸：785-1085 nt）。通过转录因子序列搜索和突变分析，确认了激活蛋白1（AP-1）结合位点位于785-1085 nt区域。 AP-1 的过表达增强了波形蛋白启动子活性。电泳迁移率变动实验和染色质免疫沉淀实验表明该结合位点被AP-1识别。通过细胞增殖实验、集落形成实验、划痕实验、细胞迁移实验和细胞侵袭实验，我们证明AP-1过表达增加了CRC细胞的增殖、迁移和侵袭。然而，当AP-1过表达的CRC细胞中vimentin被vimentin小发夹RNA敲低时，这种趋势消失了。动物实验和免疫组化表明AP-1通过调节vimentin基因促进肿瘤生长。总之，AP-1通过激活波形蛋白启动子影响体外CRC细胞的转移、侵袭和体内肿瘤生长。这项研究可能为结直肠癌发生的分子机制提供新的见解，并为结直肠癌提供潜在的治疗靶点。

"点击查看英文标题和摘要"

Vimentin affects colorectal cancer proliferation, invasion, and migration via regulated by activator protein 1

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.

更新日期：2021-05-27

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