Circular RNA circCSPP1 knockdown attenuates doxorubicin resistance and suppresses tumor progression of colorectal cancer via miR-944/FZD7 axis

Cancer Cell International

Wei Zhang¹  Linshan Luo¹  Quanlin Liu¹  Yong Wang¹  Jingfeng Song¹  Shue Wei²  Ruitao Liu²  Lanlan Xi³ 

[1] Department of Colorectal Surgery, Zhengzhou Anorectal Hospital, No. 51, Longhai East Road, 450004, Zhengzhou, China;Department of Large Intestine, Zhengzhou Anorectal Hospital, Zhengzhou, China;Department of Surgery of Traditional Chinese Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China;

关键词: CircCSPP1;    MiR-944;    FZD7;    DOX-resistant;    Tumor progression;    Colorectal cancer;   

DOI  :  10.1186/s12935-021-01855-6

来源: Springer

【 摘 要 】

BackgroundCircular RNAs (circRNAs) have been reported to play vital roles in colorectal cancer (CRC). However, only a few circRNAs have been experimentally validated and functionally described. In this research, we aimed to reveal the functional mechanism of circCSPP1 in CRC.Methods36 DOX sensitive and 36 resistant CRC cases participated in this study. The expression of circCSPP1, miR-944 and FZD7 were detected by quantitative real time polymerase chain reaction (qRT-PCR) and the protein levels of FZD7, MRP1, P-gp and LRP were detected by western blot. Cell proliferation, migration, invasion, and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, or flow cytometry analysis, respectively. The interaction between miR-944 and circCSPP1 or frizzled-7 (FZD7) was predicted by Starbase 3.0 and verified by the dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay. Xenograft tumor assay was performed to examine the effect of circCSPP1 on tumor growth in vivo.ResultsThe expression of circCSPP1 and FZD7 was upregulated while miR-944 expression was downregulated in doxorubicin (DOX)-resistant CRC tissues and cells. CircCSPP1 knockdown significantly downregulated enhanced doxorubicin sensitivity, suppressed proliferation, migration, invasion, and induced apoptosis in DOX-resistant CRC cells. Interestingly, we found that circCSPP1 directly downregulated miR-944 expression and miR-944 decreased FZD7 level through targeting to 3′ untranslated region (UTR) of FZD7. Furthermore, circCSPP1 mediated DOX-resistant CRC cell progression and doxorubicin sensitivity by regulating miR-944/FZD7 axis. Besides, circCSPP1 downregulation dramatically repressed CRC tumor growth in vivo.ConclusionOur data indicated that circCSPP1 knockdown inhibited DOX-resistant CRC cell growth and enhanced doxorubicin sensitivity by miR-944/FZD7 axis, providing a potential target for CRC therapy.

【 授权许可】

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