Circ_0000128 increases the progression of NSCLC through the miR-654-5p/OTUB1/Wnt pathway axis

Increasing evidence has shown that circRNAs play important roles in cancer. We focused on exploring the molecular mechanism of circ_0000128 in NSCLC. We first analysed the expression of circ_0000128, OTUB1 and miR-654-5p in NSCLC by RT-qPCR. The effects of circ_0000128 knockdown and upregulation of miR-654-5p expression on the phenotype of NSCLC cells were detected by plate cloning, scratch repair, transwell chamber, flow cytometry and Western blotting. The interaction relationships between circ_0000128, miR-654-5p and OTUB1 were determined by Rip and dual-luciferase assays. Furthermore, the associations between OTUB1 and miR-654-5p as well as between circ_0000128/miR-654-5p/OTUB1 were determined through retrospective experiments. Finally, the regulatory effect of circ_0000128 in mice was verified through in vivo experiments. The results revealed that in NSCLC cells and tissues, the expression of circ_0000128 and OTUB1 increased, whereas the expression of miR-654-5p decreased. Both reducing circ_0000128 expression and upregulating miR-654-5p expression increased the tumour suppressor effect of NSCLC cells and promoted apoptosis. Interestingly, upregulating OTUB1 reversed the inhibitory effect of miR-654-5p on NSCLC cells. Moreover, overexpression of OTUB1 or knockdown of miR-654-5p reversed the reduction in the invasion ability of NSCLC cells reduced by circ_0000128. Moreover, inhibiting circ_0000128 expression can suppress tumour growth in mice. In summary, our results show that circ_0000128 regulates the molecular mechanism of NSCLC through the Wnt signalling pathway by reducing miR-654-5p expression and increasing OTUB1 transcription.