Cyclin G2, a novel target of sulindac to inhibit cell cycle progression in colorectal cancer

Hongyou Zhao, Bin Yi, Zhipin Liang, Ches'Nique N. Phillips, Hui Yi Lin, Adam I. Riker, Yaguang Xi*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

5 引用 (Scopus)

摘要

Sulindac has shown significant clinical benefit in preventing colorectal cancer progression, but its mechanism of action has not been fully elucidated. We have found that sulindac sulfide (SS) is able to inhibit cell cycle progression in human colorectal cancer cells, particularly through G1 arrest. To understand the underlying mechanisms of sulindac inhibitory activity, we have demonstrated that Cyclin G2 up-regulation upon SS treatment can substantially delay cell cycle progression by enhancing the transcriptional activity of FOXO3a in human colorectal tumor cells. MiR-182, an oncogenic microRNA known to inhibit FOXO3a gene expression, is also involved in the suppressive effect of SS on cell cycle progression. This process begins with the down-regulation of miR-182, followed by the enhancement of FOXO3a transcriptional activity and the up-regulation of Cyclin G2. To further determine the clinical utility of this axis, we analyzed the expression of miR-182/FOXO3a/Cyclin G2 in human colorectal tumor samples. Our results show not only that there are significant differences in miR-182/FOXO3a/Cyclin G2 between tumors and normal tissues, but also that the synergetic effect of miR-182 and FOXO3a is associated with predicting tumor progression. Our study demonstrates a novel mechanistic axis consisting of miR-182/FOXO3a/Cyclin G2 that mediates sulindac inhibition of cell cycle progression.

源语言英语
页(从-至)320-330
页数11
期刊Genes and Diseases
8
3
DOI
出版状态已出版 - 5月 2021
已对外发布

指纹

探究 'Cyclin G2, a novel target of sulindac to inhibit cell cycle progression in colorectal cancer' 的科研主题。它们共同构成独一无二的指纹。

引用此