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Based on bioinformatic analyses and validation by qRT\u2010PCR, we identified a novel circRNA, circPPP2R4, which was upregulated in CRC tissues. Receiver operating characteristic curve analysis implied a high diagnostic value of circPPP2R4 for CRC. Additionally, high circPPP2R4 levels were positively correlated with advanced clinical stage and lymph node metastasis. Functionally, circPPP2R4 overexpression facilitated CRC cells proliferation, migration and invasion, whereas circPPP2R4 knockdown attenuated the malignant behaviors. In mouse models, circPPP2R4 overexpression remarkably promoted tumor growth and lung metastasis. Mechanistically, a series of experiments containing RIP, RNA pull\u2010down, and dual\u2010luciferase reporter assays revealed the circPPP2R4\/miR\u2010646\/FOXK1 axis in CRC. Further experiments were conducted to verify that circPPP2R4 reduced reactive oxygen species generation to exert its oncogenic function by sponging miR\u2010646 to upregulate FOXK1 expression. For the first time, we identified the regulatory role of circPPP2R4 in CRC pathogenesis, providing a potential diagnostic biomarker and therapeutic strategy for CRC.<\/jats:p>","DOI":"10.1002\/mc.23639","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T12:09:32Z","timestamp":1695730172000},"page":"106-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["circPPP2R4 promotes colorectal cancer progression and reduces ROS production through the miR\u2010646\/FOXK1 axis"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-1670","authenticated-orcid":false,"given":"Yuntian","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Colorectal and Anal Surgery Zhongnan Hospital of Wuhan University Wuhan China"},{"name":"Clinical Center of Intestinal and Colorectal Diseases of Hubei Province Wuhan China"},{"name":"Key Laboratory of 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