Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis.

Background: Circular RNAs (circRNAs) have been disclosed to exert important roles in human cancers, including gastric cancer (GC). CircRNA hsa_circ_0000144 was identified as an oncogene in GC development. The aim of our study was to explore the role of hsa_circ_0000144 in oxaliplatin (OXA) resistance of GC.

Methods: Expression levels of hsa_circ_0000144, microRNA-502-5p (miR-502-5p) and A disintegrin and metalloproteinase 9 (ADAM9) were examined by quantitative real-time PCR (RT-qPCR) or Western blot assay. The OXA resistance of GC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was performed to assess the colony formation capacity. Cell apoptosis was determined by flow cytometry and caspase 3 activity. And cell migration and invasion were detected by Transwell assay. Target association between miR-502-5p and hsa_circ_0000144 or ADAM9 was demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Moreover, role of hsa_circ_0000144 in vivo was analyzed by xenograft tumor assay.

Results: Hsa_circ_0000144 and ADAM9 were highly expressed, while miR-502-5p was downregulated in OXA-resistant GC tissues and cells. Depletion of hsa_circ_0000144 could inhibit OXA resistance, proliferation and metastasis in OXA-resistant GC cells, which was attenuated by miR-502-5p inhibition. Hsa_circ_0000144 sponged miR-502-5p to positively regulate ADAM9 expression. MiR-502-5p suppressed OXA resistance, proliferation and metastasis in OXA-resistant GC cells by targeting ADAM9. Hsa_circ_0000144 knockdown could hamper tumor growth in vivo.

Conclusion: Hsa_circ_0000144 exerted inhibitory effects on OXA resistance, proliferation and metastasis of OXA-resistant GC cells by regulating miR-502-5p/ADAM9 axis, at least in part.