已发表论文

CUL4A 通过调节上皮 - 间质转化中 H3K4 的三甲基化来促进结肠直肠癌细胞的增殖和转移

 

Authors Sui X, Zhou H, Zhu L, Wang D, Fan S, Zhao W

Received 4 August 2016

Accepted for publication 8 December 2016

Published 9 February 2017 Volume 2017:10 Pages 735—743

DOI https://doi.org/10.2147/OTT.S118897

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Jianmin Xu

Abstract: Increasing evidence suggests that CUL4A, a ubiquitin ligase, is involved in the promotion of cancer malignancy and correlated with worse clinical prognosis in several kinds of human cancers. Although its effect and mechanism on the progression of colorectal cancer (CRC) remain unknown. Our clinical data show that CUL4A protein is overexpressed, positively associated with lymph nodes status, differentiation degree, tumor size, and poor prognosis in 80 CRC patients. CUL4A overexpression promotes cell proliferation and colony formation of CRC cells. Knockdown of CUL4A inhibits cell proliferation and migration. CUL4A can significantly promote the in vitro migration of CRC cells via induction of the epithelial–mesenchymal transition process. And the modulation of CUL4A expression altered the level of H3K4 trimethylation at the E-cadherin, N-cadherin, and vimentin gene promoters, which in turn transcriptionally regulated their expression. Moreover, knockdown of CUL4A also decreased the tumor volume and tumor weight in vivo. Together, our results reveal that CUL4A plays as an oncogene in CRC and may become a potential therapeutic target in the treatment of colorectal cancer.
Keywords: colorectal cancer, CUL4A, EMT, migration, H3K4 trimethylation