Silencing Herg1 by shRNA inhibits the proliferation and invasion of osteosarcoma in vivo and in vitro

Abstract Background: Osteosarcoma is the most common malignant bone tumor of childhood, and improvements in the survival rates have reached a plateau phase. This study was aimed to explore the the importance of the human ether-a-go-go-related potassium channel (Herg1) in the proliferation and invasion of osteosarcoma.Methods: The effects of Herg1 silenced on osteosarcoma cell proliferation and invasion were detected by were detected by CCK-8 assay, wound healing assay and transwell assay, respectively. Tandem affinity purification, mass spectrometry and Dual luciferase reporter assay were used to find out possible molecules responsible for the action of Herg1 on osteosarcoma cells. Nude mouse model was used to investigate the in vivo functions of Herg1. Results: Herg1 silencing by shRNA significantly suppressed the proliferation and invasion of osteosarcoma cells in vitro as well as tumorigenicity and metastasis in nude mice. Moreover, Herg1 promoted osteosarcoma progression via turning off Hippo signaling pathway, leading to the activation of Yes-associated protein (YAP). Mechanistically, Herg1 co-localized and interacted with NF2 (also called Merlin), and this interaction probably caused the de-phosphorylation of MST1/2 and LATS1/2, which drove YAP nuclear translocation and transcriptional activation. Conclusion: Herg1 acts as an oncogene in osteosarcoma and may therefore serve as a useful therapeutic target for osteosarcoma patients.