NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

Journal of Experimental & Clinical Cancer Research

Jin Zhou¹  Dongyang Wang²  Longgang Wang³  Xiuwen Kang⁴  Lei Zhou⁵  Jinxiang Guo⁶ 

[1] Department of Endocrinology, Affiliated Yantai Yuhuangding Hospital of QingdaoUniversity Medical, 264000, Yantai, China;Department of Endoscopy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 250117, Jinan, China;Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 250117, Jinan, China;Department of Intensive Care Unit, The First People’s Hospital of Lianyungang, 222000, Lianyungang, China;Department of Oncological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin District, 250117, Jinan, Shandong Province, China;Department of Respiratory Medicine, Taian Municipal Hospital, 271000, Taian, China;

关键词: Colon cancer;    Cancer stem cells;    NF-κB;    Stemness;    microRNA-195-5p;    microRNA-497-5p;   

DOI  :  10.1186/s13046-020-01704-w

来源: Springer

【 摘 要 】

BackgroundColon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer.MethodsTumor samples and matched normal samples were obtained from 35 colon cancer cases. CSCs were isolated from human colon cancer cell lines, where the stemness of the cells was evaluated by cell viability, colony-forming, spheroid-forming, invasion, migration, and apoptosis assays. NF-κB activation was then performed in subcutaneous tumor models of CSCs by injecting lipopolysaccharides (LPS) i.p.ResultsWe found that NF-κB activation could reduce the expression of miR-195-5p and miR-497-5p, where these two miRNAs were determined to be downregulated in colon cancer tissues, cultured colon CSCs, and LPS-injected subcutaneous tumor models. Elevation of miR-195-5p and miR-497-5p levels by their specific mimic could ablate the effects of NF-κB on the stemness of colon cancer cells in vivo and in vitro, suggesting that NF-κB could maintain the stemness of colon cancer cells by downregulating miR-195-5p/497–5p. MCM2 was validated as the target gene of miR-195-5p and miR-497-5p in cultured colon CSCs. Overexpression of MCM2 was shown to restore the stemness of colon cancer cells in the presence of miR-195-5p and miR-497-5p, suggesting that miR-195-5p and miR-497-5p could impair the stemness of colon cancer cells by targeting MCM2 in vivo and in vitro.ConclusionsOur work demonstrates that the restoration of miR-195-5p and miR-497-5p may be a therapeutic strategy for colon cancer treatment in relation to NF-κB activation.

【 授权许可】

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