CircDDX17 reduces 5-fluorouracil resistance and hinders tumorigenesis in colorectal cancer by regulating miR-31-5p/KANK1 axis

T.-J. Ren, C. Liu, J.-F. Hou, F.-X. Shan

Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China. gfwnhp@163.com

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• Oncology

OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Chemotherapy resistance is a considerable obstacle to CRC treatment. Circular RNAs (circRNAs) are involved in the pathogenesis of many cancers. This study aimed to investigate the role and molecular basis of DEAD-box helicase 17 circRNA (circDDX17) in 5-fluorouracil (5-Fu) sensitivity and CRC progression.

MATERIALS AND METHODS: The levels of circDDX17, microRNA-31-5p (miR-31-5p) and kidney ankyrin repeat-containing protein 1 (KANK1) were detected by quantitative real-time PCR or western blot assay. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis rate was monitored by flow cytometry. Cell invasion capacity was evaluated by transwell assay. Western blot assay was conducted to measure the expression of matrix metallopeptidase 9 (MMP9) and E-cadherin. The interaction among circDDX17, miR-31-5p and KANK1 was indicated by bioinformatics analysis and dual-luciferase reporter assay. Xenograft assay was performed to analyze tumor growth and 5-Fu sensitivity in vivo.

RESULTS: CircDDX17 and KANK1 were down-regulated, while miR-31-5p was upregulated in CRC tissues and cells. Upregulation of circDDX17 enhanced 5-Fu sensitivity and impeded CRC development. CircDDX17 inhibited 5-Fu resistance and CRC progression via sponging miR-31-5p. Besides, KANK1 depletion attenuated the effect of circDDX17 upregulation on chemosensitivity and CRC progression. CircDDX17 regulated KANK1 expression by binding to miR-31-5p. Moreover, circDDX17 overexpression blocked tumor growth and elevated 5-Fu sensitivity in vivo.

CONCLUSIONS: Upregulation of circDDX17 strengthened chemosensitivity of CRC to 5-Fu and blocked CRC progression by regulating miR-31-5p/KANK1 axis, which might provide an effective treatment strategy for CRC patients.

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