Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway

Cancer Cell International

Research

Wei Zhan¹  Gang Chen²  Wen Chen²  Haiyu Cheng²  Jiandong Zhang²  Zhongsheng Chen²  Dongbing Jiang²  Shunkang Yan² 

[1] Department of colorectal surgery, The Affiliated Hospital of Guizhou Medical University, No.28 Guiyi Street, Yunyan District, 550004, Guiyang City, Guizhou, China;Guizhou Medical University, Guiyang, China;

关键词: Hsa_circRNA_102051;    miR-203a;    BPTF;    Notch;    Colorectal cancer;   

DOI  :  10.1186/s12935-023-03026-1

 received in 2023-03-02, accepted in 2023-08-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells.MethodsCircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative real-time PCR was used to detect the relative RNA expression in CRC cells and samples. The effects of hsa_circRNA_102051 on biological functions in CRC cells were accessed both in vitro and in vivo. FISH, RIP and luciferase reporter assay were conducted to confirm the regulatory correlations between hsa_circRNA_102051 and miR-203a, as well as miR-203a and BPTF. Xenograft models were applied to further verify the impacts and fluctuations of hsa_circRNA_102051/miR-203a/BPTF. Moreover, the mechanism how hsa_circRNA_102051 affected the Notch signals was also elucidated.ResultsHsa_circRNA_102051 was up-regulated in CRC tissues and cell lines, capable to promote the growth and invasion of CRC. In addition, hsa_circRNA_102051 could enhance stemness of CRC cells. BPTF was identified as downstream factors of hsa_circRNA_102051, and miR-203a was determined directly targeting both hsa_circRNA_102051 and BPTF as an intermediate regulator. Hsa_circRNA_102051 in CRC could block miR-203a expression, and subsequently activated BPTF. Hsa_circRNA_102051/miR-203a/BPTF axis modulated stemness of CRC cells by affecting Notch pathway.ConclusionsOur findings provided new clues that hsa_circRNA_102051 might be a potential predictive or prognostic factor in CRC, which induced the fluctuation of downstream miR-203a/BPTF, and subsequently influenced tumor growth, activities and stemness. Thereinto, the Notch signals were also involved. Hence, the hsa_circRNA_102051/miR-203a/BPTF axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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