Gu Wanli, Chen Peng, Ren Peng, Wang Yanhai, Li Xiaobing, Gong Mingzhi
Department of Orthopaedics, The Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Obstetrical Department, The Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Onco Targets Ther. 2021 Apr 30;14:2917-2927. doi: 10.2147/OTT.S264786. eCollection 2021.
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.
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.
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 3'UTR 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.
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.
骨肉瘤（OS）是一种具有高转移潜能的恶性骨肿瘤。作为细胞凋亡的调控因子，TATA盒结合蛋白（TBP）相关因子9B（TAF9B）在肿瘤中的研究较少。
我们通过过表达和敲低来研究TAF9B在OS细胞中的作用及机制。进行CCK8、集落形成、Transwell和流式细胞术分析以检测增殖、迁移、侵袭和凋亡。
TAF9B过表达促进OS细胞的增殖、迁移和侵袭，而TAF9B敲低则产生相反的结果。TAF9B通过上调Bcl-2和下调Bax及Cleaved-caspase-3来抑制细胞凋亡。通过starBase分析发现，miR-7-5p可与TAF9B的3'UTR区域结合，双荧光素酶报告系统检测进一步证实了这一点。miR-7-5p下调MG63和U2OS细胞中TAF9B的表达。转染miR-7-5p模拟物后OS细胞的增殖和侵袭受到抑制，转染miR-7-5p抑制剂后则受到促进。TAF9B可挽救miR-7-5p对OS细胞的抑制作用。TAF9B还激活AKT/mTOR信号通路。
根据我们的结果，miR-7-5p抑制TAF9B的翻译，进而通过AKT/mTOR信号通路抑制OS细胞的生长和转移，从而表明miR-7-5p和TAF9B作为人类OS治疗靶点的潜在价值。
