OncoTargets and Therapy (Feb 2020)
circHIPK3 Promotes Cell Proliferation and Migration of Gastric Cancer by Sponging miR-107 and Regulating BDNF Expression
Abstract
Juan Wei,1,2 Hanfeng Xu,2 Wei Wei,3 ZhaoJing Wang,4 QiJia Zhang,2 Wei De,5 Yongqian Shu1 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Oncology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Gastrosurgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, People’s Republic of China; 4Department of Digestive Oncology Surgery, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 5Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Yongqian ShuDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaEmail [email protected] Wei DeDepartment of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaEmail [email protected]: Circular RNAs (circRNAs) play important regulatory roles in cancer development. However, the mechanisms by which circRNAs regulate gene expression in gastric cancer (GC) remain unclear.Methods: Human GC samples and their matched normal adjacent tissues were obtained from 30 patients to assess the expression of circHIPK3 and its relationship with GC proliferation and migration. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circHIPK3 in GC proliferation and migration, and its underlying molecular mechanisms.Results: Using a circRNA microarray we found a circRNA termed circHIPK3 that performed a significant regulatory role in GC. circHIPK3 was further confirmed to be upregulated in all GC tissues and cells tested. Furthermore, circHIPK3 levels were associated with Tumor & Lymph Node & Metastasis(TNM) stage (P = 0.032). The area under the receiver operating characteristic curve (ROC) was 0.743 (95% confidence interval 0.615– 0.872; P = 0.001). CCK-8, colony formation, Transwell and EdU assays were performed to evaluate the effects of circHIPK3 on cell proliferation and migration in GC. Moreover, circHIPK3 was identified as a sponge of miR-107, and as such it regulated brain-derived neurotrophic factor (BDNF), which plays a pivotal role in the development of GC.Conclusion: circHIPK3 represents a novel potential biomarker and therapeutic target of GC.Keywords: circHIPK3, miR-107, BDNF, proliferation, migration, gastric cancer
