OncoTargets and Therapy (May 2020)
Downregulation of miR-575 Inhibits the Tumorigenesis of Gallbladder Cancer via Targeting p27 Kip1
Abstract
Yiyu Qin,1,* Wunan Mi,2,* Cheng Huang,1 Jian Li,1 Yizheng Zhang,2 Yang Fu2 1Clinical Medical College, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu 224005, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiyu QinClinical Medical College, Jiangsu Vocational College of Medicine, 283 Jiefang South Road, Yancheng, Jiangsu 224005, People’s Republic of ChinaEmail [email protected] FuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan 450052, People’s Republic of ChinaEmail [email protected]: Gallbladder cancer (GBC) is the most common biliary tract malignant cancer worldwide. It has been reported that microRNA-575 (miR-575) was involved in the tumorigenesis of many cancers. However, the role of miR-575 during the progression of GBC remains largely unknown.Methods: The expression of miR-575 in GBC cells was detected by quantitative real-time polymerase chain reaction. The proliferation of GBC cells was examined by CCK-8 assay and Ki-67 staining. Apoptosis of GBC cells was measured by flow cytometry, and cell invasion was tested by transwell assay. Moreover, protein expressions in GBC cells were evaluated using Western blot. The target gene of miR-575 was predicted using Targetscan and miRDB. Finally, xenograft tumor model was established to verify the function of miR-575 in GBC in vivo.Results: Our findings indicated that miR-575 antagonist decreased the proliferation and invasion of GBC cells. In addition, miR-575 antagonist significantly induced apoptosis of GBC cells via inducing G1 arrest. Meanwhile, p27 Kip1 was found to be a direct target of miR-575 with luciferase reporter assay. Moreover, miR-575 antagonist significantly decreased the expressions of CDK1 and cyclin E1 and upregulated the levels of cleaved caspase3 and p27 Kip1 in GBC cells. Finally, miR-575 antagonist notably suppressed GBC tumor growth in vivo.Conclusion: Downregulation of miR-575 significantly inhibited the tumorigenesis of GBC via targeting p27 Kip1. Thus, miR-575 might be a potential novel target for the treatment of GBC.Keywords: miR-575, p27 Kip1, gallbladder cancer
