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E2F3促进癌症生长,并且在人类黑色素瘤中通过拷贝数变异而过度表达。

E2F3 promotes cancer growth and is overexpressed through copy number variation in human melanoma.

作者信息

Feng Zhicai, Peng Cheng, Li Daojiang, Zhang Danhua, Li Xu, Cui Fengran, Chen Yanhong, He Quanyong

机构信息

Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China,

Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.

出版信息

Onco Targets Ther. 2018 Aug 30;11:5303-5313. doi: 10.2147/OTT.S174103. eCollection 2018.

Abstract

INTRODUCTION

Melanoma is a malignant tumor that seriously affects patients. The pathogenesis of malignant melanoma is complex, and the cell cycle is closely related to tumor progression. Based on the catalog of cancer somatic mutations, we found that overexpression of the gene ranked first in percentage increase in not only melanoma but also in all human cancer tissues. However, there are few studies on the high expression of and its carcinogenic mechanism in melanoma.

METHODS AND RESULTS

We found that showed extensive copy number amplification that was positively correlated with the expression level. Patients with high copy number had a significantly poorer prognosis. We also found that levels were significantly negatively correlated with promoter methylation. However, we showed that the promoter region is hypomethylated, and in normal cells or tumor cells, the methylation level did not correlate with expression. Finally, we knocked down the gene in melanoma cells by shRNA. Colony formation, anchorage-dependent growth, and EdU cell proliferation experiments showed a significant decrease in proliferation. Flow cytometry showed a significant increase in the G0/G1 ratio.

CONCLUSION

It can be speculated that copy number amplification and other mechanisms result in the high expression of in melanoma, which promotes tumor progression by involving the cell cycle. is a good target for the treatment of melanoma.

摘要

引言

黑色素瘤是一种严重影响患者的恶性肿瘤。恶性黑色素瘤的发病机制复杂,细胞周期与肿瘤进展密切相关。基于癌症体细胞突变目录,我们发现该基因的过表达在黑色素瘤以及所有人类癌症组织中的百分比增加排名第一。然而,关于该基因在黑色素瘤中的高表达及其致癌机制的研究很少。

方法与结果

我们发现该基因显示出广泛的拷贝数扩增,且与表达水平呈正相关。拷贝数高的患者预后明显较差。我们还发现该基因水平与启动子甲基化呈显著负相关。然而,我们发现该基因启动子区域是低甲基化的,并且在正常细胞或肿瘤细胞中,甲基化水平与表达无关。最后,我们通过shRNA敲低黑色素瘤细胞中的该基因。集落形成、锚定依赖性生长和EdU细胞增殖实验显示增殖显著降低。流式细胞术显示G0/G1比率显著增加。

结论

可以推测,拷贝数扩增等机制导致黑色素瘤中该基因的高表达,其通过涉及细胞周期促进肿瘤进展。该基因是黑色素瘤治疗的良好靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72a0/6124799/4d539bb5aef9/ott-11-5303Fig1.jpg

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