circPPP2R4 promotes colorectal cancer progression and reduces ROS production through the miR-646/FOXK1 axis
Yuntian Hong
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorBaoxiang Chen
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorChun Wang
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
Search for more papers by this authorRui Gui
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
Search for more papers by this authorXiang Zhai
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorQun Qian
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorCorresponding Author
Xianghai Ren
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Correspondence Congqing Jiang, Xiaoyu Xie, and Xianghai Ren, Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xiaoyu Xie
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Correspondence Congqing Jiang, Xiaoyu Xie, and Xianghai Ren, Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Congqing Jiang
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Correspondence Congqing Jiang, Xiaoyu Xie, and Xianghai Ren, Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorYuntian Hong
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorBaoxiang Chen
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorChun Wang
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
Search for more papers by this authorRui Gui
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
Search for more papers by this authorXiang Zhai
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorQun Qian
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Search for more papers by this authorCorresponding Author
Xianghai Ren
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Correspondence Congqing Jiang, Xiaoyu Xie, and Xianghai Ren, Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xiaoyu Xie
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Correspondence Congqing Jiang, Xiaoyu Xie, and Xianghai Ren, Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Congqing Jiang
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Key Laboratory of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China
Correspondence Congqing Jiang, Xiaoyu Xie, and Xianghai Ren, Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorYuntian Hong, Baoxiang Chen, and Chun Wang contributed equally to this work.
Abstract
Circular RNAs (circRNAs) play important roles in colorectal cancer (CRC) development and progression. This study aimed to investigate the function and molecular mechanism of circPPP2R4 in CRC. Based on bioinformatic analyses and validation by qRT-PCR, 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-down, and dual-luciferase reporter assays revealed the circPPP2R4/miR-646/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-646 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.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request. Data supporting the present study are available upon request by contact with the corresponding author.
Supporting Information
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| mc23639-sup-0001-Supplementary_Figures_and_Tables.pdf11.2 MB | Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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