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

Genes & Diseases 2021年第3期8卷 320-330页

作者： Hongyou Zhao Bin Yi Zhipin Liang Ches’Nique Phillips Hui-Yi Lin Adam I.Riker Yaguang Xi Department of Genetics and Stanley S.Scott cancer Center Louisiana State University Health Sciences CenterNewOrleans70112USA School of Public Health Louisiana State University Health Sciences CenterNew Orleans70112USA geaton and joann decesaris cancer institute Anne Arundel Medical CenterLuminis HealthAnnapolisMD21401USA

Sulindac has shown significant clinical benefit in preventing colorectal cancer pro-gression,but its mechanism of action has not been fully *** have found that sulin-dac sulfide(SS)is able to inhibit cell cycle progression in human colorectal cancer cells,particularly through G1 *** understand the underlying mechanisms of sulindac inhibitory activity,we have demonstrated that Cyclin G2 up-regulation upon SS treatment can substan-tially delay cell cycle progression by enhancing the transcriptional activity of FOXO3a in human colorectal tumor ***-182,an oncogenic microRNA known to inhibit FOXO3a gene expres-sion,is also involved in the suppressive effect of SS on cell cycle *** process be-gins with the down-regulation of miR-182,followed by the enhancement of FOXO3a transcriptional activity and the up-regulation of Cyclin *** further determine the clinical utility of this axis,we analyzed the expression of miR-182/FOXO3a/Cyclin G2 in human colo-rectal tumor *** results show not only that there are significant dfferences 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 *** study dem-onstrates a novel mechanistic axis consisting of miR-182/FOXO3a/Cyclin G2 that mediates su-lindac inhibition of cell cycle progression.

关键词： Cell cycle Colorectal cancer Gene regulation miRNA Sulindac

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