OncoTargets and Therapy (Apr 2021)
Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis
Abstract
Haifeng Gao,1,* Jiajia Xu,2,* Fen Qiao,3 Liangjun Xue4 1Department of Clinical Laboratory, Baoji Central Hospital, Baoji City, 721008, Shaanxi Province, People’s Republic of China; 2Department of Organic Chemistry and Pharmaceutical Chemistry, Pharmaceutical College of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Pediatrics, Baoji Central Hospital, Baoji City, Shaanxi Province, People’s Republic of China; 4Department of Radiotherapy, Yijishan Hospital of Wannan Medical College, Wuhu City, Anhui Province, 241001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liangjun XueDepartment of Radiotherapy, Yijishan Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu City, Anhui Province, 241001, People’s Republic of ChinaTel +86 553-5738279Email [email protected]: 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.Keywords: GC, OXA resistance, hsa_circ_0000144, miR-502-5p, ADAM9, OXA-resistant GC cells
