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JQ‑1 InhibitsnColon Cancer Proliferation vianSuppressing Wnt/β-Catenin Signaling and miR-21 JQ‑1通过抑制Wnt/β-Catenin信号和miR-21抑制结肠癌增殖

Figshare Pub Date : 2018-04-11 DOI: 10.1021/acs.chemrestox.7b00346.s001

Yan Zhang (8098), Suli Tian (397882), Jidong Xiong (5087945), Yongxu Zhou (5087948), Hongyu Song (1825576), Chang Liu (35901)

{"title":"JQ‑1 InhibitsnColon Cancer Proliferation vianSuppressing Wnt/β-Catenin Signaling and miR-21","authors":"Yan Zhang (8098), Suli Tian (397882), Jidong Xiong (5087945), Yongxu Zhou (5087948), Hongyu Song (1825576), Chang Liu (35901)","doi":"10.1021/acs.chemrestox.7b00346.s001","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.7b00346.s001","url":null,"abstract":"Bromodoamin and extraterminaln(BET) protein inhibitors are a novelnclass of cancer therapeutics. Here we aim to investigate the efficacynand mechanism of JQ-1, a potent BET inhibitor, in colon cancer therapy.nJQ-1 was used to treat SW480 colon cancer mouse xenografts. The tumornsize and mouse survival were recorded. Cell apoptosis was evaluatednby Annex V-FIC/PI flow cytometry. ChIP-q-PCR analysis was used tonassess the H3K27 trimethylation (H3K27m3) of the p16 promoter. Wntnsignaling was evaluated by Nkd2 and β-catenin levels. RT-PCRnwas used to evaluate the level of miR-21. MiR-21 was overexpressednwith a lentiviral system and was used to evaluate the relationshipnbetween miR-21 and JQ-1. JQ-1 significantly reduced tumor growth,nimproved mouse survival, and induced apoptosis. JQ-1 epigeneticallyninhibited the H3K27me3 promoter activity, promoting p16 expression.nNkd2 and β-catenin were upregulated and downregulated by JQ-1,nrespectively. MiR-21 was downregulated by JQ-1. MiR-21 overexpressionncompensated for proliferation inhibition by JQ-1. Nkd2 levels werenalso downregulated by miR-21 overexpression. JQ-1 is effective inninhibiting colon cancer. We revealed that the mechanism of JQ-1 actionnis associated with its regulation of Wnt/β-catenin signalingnand miR-21 levels.","PeriodicalId":521705,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147884467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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