Circ_0060967 contributes to colorectal cancer progression by sponging miR-1184 to up-regulate SRC proto-oncogene

Background and study aims: Circular RNAs (circRNAs) are closely associated with cancer pathogenesis. The purpose of our current study was to explore the role and mechanism of circ_0060967 in colorectal cancer (CRC) development. Patients and methods: Human CRC specimens and paired healthy tissues were used to examine variable expres-sion. The expression of circ_0060967 and microRNA (miR)-1184 was examined by quantitative reverse transcription-PCR. The protein levels of proliferating cell nuclear antigen, BCL2-associated X, apoptosis regulator (Bax), proto-oncogene nonreceptor tyrosine kinase Src (SRC), nuclear factor-& kappa;B inhibitor alpha (I & kappa;B & alpha;), phos-phorylated-I & kappa;B & alpha; (p-I & kappa;B & alpha;), RELA proto-oncogene, nuclear factor-& kappa;B subunit (p65), and phosphorylated-p65 (p-p65) were determined by western blot. Proliferation and motility of HCT-116 and SW480 CRC cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and transwell assays, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay were used to determine the binding relation between miR-1184 and circ_0060967 or SRC. Animal studies were used to detect the role of circ_0060967 in CRC cell tumorigenicity. Results: Circ_0060967 abundance was enhanced in human CRC tissue samples versus paired normal colorectal tissues and in HCT-116 and SW480 CRC cells versus normal HCO cells. Decreased expression of circ_0060967 could suppress cell growth, motility, and invasiveness of CRC cells in vitro and tumor growth in vivo. Circ_0060967 sponged miR-1184, and miR-1184 targeted SRC. Furthermore, we also found circ_0060967 affected cell growth by modulating miR-1184/SRC axis in CRC. Conclusion: This study demonstrates a novel circ_0060967/miR-1184/SRC regulatory cascade in affecting CRC cell malignant behaviors, which can have a broad effect on the field of molecularly targeted therapeutics.