Fig. 4.

circRTN4 promotes HOTTIP expression by sponging miR-497-5p in PDAC. A Schematic diagram showing the putative binding sites of circRTN4 on miR-497-5p. B Reduction of luciferase activity of circRTN4-reporter in HEK293 cells co-transfected with miR-497-5p mimics with potential binding sites on circRTN4. C Mutating the miR-497-5p binding site on circRTN4-reporter restored the luciferase activity in HEK293 cells co-transfected with miR-497-5p mimics. D CircRTN4 was enriched by biotin-labelled miR-497-5p mimics in PANC-1 cells. E CircRTN4 knockdown increased the expression of miR-497-5p in PANC-1 cells. F Transfecting miR-497-5p mimics did not alter the expression of circRTN4 in PANC-1 cells. G-H (G) HOTTIP and (H) HOAX13 level were reduced after circRTN4 knockdown in PDAC cells. I CircRTN4 knockdown in mice subcutaneous tumors inhibited HOXA13 expression, revealed by immunohistochemical staining. J HOTTIP and HOXA13 expression were rescued in circRTN4-overexpressing HPDE cells after transfecting miR-497-5p mimics. K The upregulated HOTTIP were positively correlated with circRTN4 level in PDAC primary tumors. Data represent mean ± SD from at least three independent experiments (*p < 0.05; **p < 0.01; ***p < 0.001)