Hsa-circ-0081143 promotes cisplatin resistance in gastric cancer by targeting miR-646/CDK6 pathway

Abstract

Background: Increasing studies indicated that circRNAs play critical roles in tumor progression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain largely unclear. Methods: Microarray assay was used to screen the abnormally expressed circRNAs in GC. Cell viability assay, transwell assay and in vivo assay were performed to assess the effects of hsa-circ-0081143 on GC cells. Next, interaction between hsa-circ-0081143 and miR-646 was detected by luciferase reporter assay and RNA pull-down assay. Results: High throughput microarray assay showed that hsa-circ-0081143 was upregulated in GC tissues, which was further confirmed by qRT-PCR. Correlation analysis showed that high hsa-circ-0081143 expression was associated with the advanced TNM stage, lymphnode metastases, and poor overall survival of GC patients. Hsa-circ-0081143 inhibition decreased GC cells viability, invasion ability and induced the sensitivity of GC cells to cisplatin (DDP) in vitro. Mechanistically, we showed that hsa-circ-0081143 could act as an endogenous sponge by directly binding to miR-646 and downregulation of miR-646 efficiently reversed the inhibition of CDK6 induced by hsa-circ-008114 knockdown. Additionally, hsa-circ-0081143 silencing suppressed the tumorigenesis and remarkably enhance DDP inhibitory effects of GC cells in vivo. Conclusions: Our study indicated a novel regulatory loop that hsa-circ-0081143/miR-646/CDK6 axis in GC progression. These data suggested that hsa-circ-0081143 might act as a potential novel therapeutic strategy for GC treatment.