miR-455-3p Functions as a Tumor Suppressor by Restraining Wnt/β-Catenin Signaling via TAZ in Pancreatic Cancer

Ting Zhan, 1,* Qingxi Zhu, 1,* Zheng Han, 1 Jie Tan, 1 Meng Liu, 1 Weijie Liu, 1 Wei Chen, 1 Xiaoli Chen, 1 Xueting Chen, 2 Junsheng Deng, 2 Xia Tian, 1 Xiaodong Huang 1 1Department of Gastroenterology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan 430060, People’s Republic of China; 2Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Huang; Xia Tian Tel +86 1388619054; +86 13871480868Email 13297056720@163.com; hcwy100@163.comBackground: Pancreatic cancer (PC) is a highly invasive tumor with a poor prognosis, short overall survival rate and few chemotherapeutic choices. Despite the importance of finding ways to treat pancreatic cancer, the mechanisms of tumor progression have not been fully elucidated. microRNA-455-3p (miR-455-3p) has been reported to play an important role in several cancers, but its function in pancreatic cancer remains unclear.Methods: To investigate the biological functions, miRNAs mimics or inhibitors were transfected into pancreatic cancer cells. Flow cytometry was used to detect cell apoptosis. Wound healing and Transwell assays were employed to observe cell invasion and migration abilities. The expression of Bcl-2, Bax, caspase-3, E-cadherin, N-cadherin, Snail, β-Catenin, c-Myc and Cyclin D1 were evaluated by qPCR and Western blot.Results: We confirmed that inhibition of miR-455-3p decreases cell apoptosis and increases cell migration, invasion and EMT of pancreatic cancer, whereas forced overexpression of miR-455-3p has the opposite effect. Furthermore, we demonstrated that the tumor suppression effects of miR-455-3p were partially reversed by TAZ overexpression. In addition, miR-455-3p led to inactivation of Wnt/β-catenin signaling in pancreatic cancer cells, and TAZ overexpression restored the inhibition of Wnt/β-catenin signaling.Conclusion: Taken together, our data demonstrated that miR-455-3p functions as an important tumor suppressor that suppresses the Wnt/β-catenin signaling pathway via TAZ to inhibit tumor progression in pancreatic cancer. We conclude that the miR-455-3p/TAZ/Wnt axis may be a potential therapeutic target for pancreatic cancer.Keywords: miR-455-3p, Wnt, apoptosis, metastasis, EMT