OncoTargets and Therapy (Apr 2021)
Downregulation of TAF9B by miR-7-5p Inhibits the Progression of Osteosarcoma
Abstract
Wanli Gu,1 Peng Chen,1 Peng Ren,1 Yanhai Wang,2 Xiaobing Li,3 Mingzhi Gong1 1Department of Orthopaedics, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Obstetrical Department, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 3Institute of Basic Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Mingzhi GongDepartment of Orthopaedics, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, 250033, Shandong, People’s Republic of ChinaTel +86 17660081696Email [email protected]: Osteosarcoma (OS) is a malignant bone tumor with high metastatic potential. As a regulatory factor of apoptosis, TATA-box binding protein (TBP) associated factor 9B (TAF9B) is rarely studied in tumors.Methods: We investigated the role and mechanism of TAF9B in OS cells by overexpression and knockdown. CCK8, colony formation, transwell, and flow cytometry analysis were performed to detect proliferation, migration, invasion, and apoptosis.Results: TAF9B overexpression promotes the proliferation, migration, and invasion of OS cells, while TAF9B knockdown gives the opposite result. TAF9B inhibits apoptosis by upregulating Bcl-2 and downregulating Bax and Cleaved-caspase-3. Through starBase analysis, it was found that miR-7-5p can bind to the 3ʹUTR region of TAF9B, which is further confirmed by the dual luciferase reporter system assay. MiR-7-5p downregulates the expression of TAF9B in MG63 and U2OS cells. The proliferation and invasion of OS cells are inhibited after miR-7-5p mimics transfection and are promoted after miR-7-5p inhibitor transfection. TAF9B rescues the inhibitory effect of miR-7-5p on OS cells. TAF9B also activates the AKT/mTOR signaling pathway.Conclusion: According to our results, miR-7-5p inhibits the translation of TAF9B and then suppresses growth and metastasis through the AKT/mTOR signaling pathway in OS cells, thereby indicating the potential value of miR-7-5p and TAF9B as therapeutic targets for human OS.Keywords: TAF9B, osteosarcoma, miR-7-5p, 3ʹUTR
