MicroRNA-200b acts as a tumor suppressor in osteosarcoma via targeting ZEB1

Abstract

Yusheng Li,1 Chao Zeng,1 Min Tu,2 Wei Jiang,3 Zixun Dai,4 Yuling Hu,5 Zhenhan Deng,1 Wenfeng Xiao1 1Department of Orthopedics, Xiangya Hospital Central South University, Changsha, Hunan, 2Department of Orthopedics, Second People’s Hospital of Jingmen, Jingmen, Hubei, 3Department of Bone and Joint, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, 4Department of Orthopedics, The Affiliated Cancer Hospital of Xiangya School of Medicine, 5Department of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China Abstract: Osteosarcoma is the most common type of cancer that develops in bone, mainly arising from the metaphysis of the long bones. MicroRNA (miR)-200b has been found to generally act as a tumor suppressor in multiple types of human cancers. However, the detailed role of miR-200b in osteosarcoma still remains to be fully understood. This study aimed to investigate the exact role of miR-200b in the progression of osteosarcoma and the underlying mechanism. Real-time reverse transcription-polymerase chain reaction data showed that miR-200b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Low miR-200b level was associated with the advanced clinical stage and positive distant metastasis. Besides, it was also downregulated in osteosarcoma cell lines (U2OS, Saos2, HOS, and MG63) compared to normal osteoblast cell line NHOst. In vitro study showed that restoration of miR-200b led to a significant decrease in proliferation, migration, and invasion of osteosarcoma cells. Moreover, ZEB1 was identified as a target gene of miR-200b, and its expression levels were negatively mediated by miR-200b in osteosarcoma cells. In addition, ZEB1 was significantly upregulated in osteosarcoma cells compared to the normal osteoblast cell line NHOst, and inhibition of ZEB1 expression also suppressed the proliferation, migration, and invasion in osteosarcoma cells. Finally, we showed that ZEB1 was frequently upregulated in osteosarcoma tissues compared to their matched adjacent normal tissues, and its expression was reversely correlated to the miR-200b levels in osteosarcoma tissues. Based on these findings, our study suggests that miR-200b inhibits the proliferation, migration, and invasion of osteosarcoma cells, probably via the inhibition of ZEB1 expression. Therefore, miR-200b/ZEB1 may become a potential target for the treatment of osteosarcoma. Keywords: osteosarcoma, microRNA-200b, proliferation, migration, invasion, metastasis

Keywords

• Osteosarcoma
• microRNA-200b
• proliferation
• migration
• invasion
• metastasis