Wang Peipei, Zhu Jianwei, Long Qingqin, Wang Yan, Xu Huihua, Tao Huimin, Wu Biwen, Li Jiajun, Wu Yong, Liu Sihong
Department of Oncology, the Second Affiliated Hospital, and School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, Guangdong 510180, PR China.
Department of Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, PR China.
J Bone Oncol. 2023 Jun 27;41:100491. doi: 10.1016/j.jbo.2023.100491. eCollection 2023 Aug.
Our previous report has identified a lncRNA SATB2-AS1, which was significantly up-regulated in osteosarcoma tissue and promotes the proliferation of osteosarcoma cells in . However, the mechanisms of SATB2-AS1 regulating the growth and metastasis of osteosarcoma cells in and its role in the prognosis of osteosarcoma patients are still unclear. In this study, the transcriptome sequencing data of 87 patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and 7 patients from our clinical center (GZFPH) was used to evaluate the importance of SATB2-AS1 and SATB2 on the prognosis. The effect of SATB2-AS1 on the growth and metastasis of osteosarcoma cells in was verified by a mouse tumor model. The potential mechanisms of SATB2-AS1 regulating SATB2 were further explored by dual-luciferase reporter gene assay, RNA pull-down assay, and bioinformatics analysis. The results suggested that increased co-expression of SATB2-AS1 and SATB2 was significantly associated with poor overall survival (OS) and relapse-free survival (RFS), and was a biomarker for risk stratification in patients with osteosarcoma. Mechanistically, SATB2-AS1 promotes tumor growth and lung metastasis by regulating SATB2 in . SATB2-AS1 directly binds to POU3F1 for mediating SATB2 expression in MNNG/HOS cells. In addition, SATB2-AS1 and SATB2 might be potential immunomodulators for negatively affecting immune cell infiltration by the IL-17 signaling pathway. In summary, SATB2-AS1 promoted tumor cell growth and lung metastasis by activating SATB2, thereby associated with poor prognosis in patients with osteosarcoma, which indicated that SATB2-AS1 and SATB2 might be novel biomarkers for risk stratification and promising therapeutic targets for osteosarcoma.
我们之前的报告鉴定出一种长链非编码RNA SATB2-AS1,其在骨肉瘤组织中显著上调,并促进骨肉瘤细胞的增殖。然而,SATB2-AS1调控骨肉瘤细胞生长和转移的机制及其在骨肉瘤患者预后中的作用仍不清楚。在本研究中,我们使用了来自治疗应用研究以产生有效治疗方法(TARGET)数据库的87例骨肉瘤患者以及我们临床中心(GZFPH)的7例患者的转录组测序数据,来评估SATB2-AS1和SATB2对预后的重要性。通过小鼠肿瘤模型验证了SATB2-AS1对骨肉瘤细胞生长和转移的影响。通过双荧光素酶报告基因检测、RNA下拉检测和生物信息学分析进一步探索了SATB2-AS1调控SATB2的潜在机制。结果表明,SATB2-AS1和SATB2共表达增加与总生存期(OS)和无复发生存期(RFS)较差显著相关,并且是骨肉瘤患者风险分层的生物标志物。从机制上讲,SATB2-AS1通过调控SATB2促进肿瘤生长和肺转移。SATB2-AS1直接与POU3F1结合以介导MNNG/HOS细胞中SATB2的表达。此外,SATB2-AS1和SATB2可能是潜在的免疫调节剂,通过IL-17信号通路对免疫细胞浸润产生负面影响。总之,SATB2-AS1通过激活SATB2促进肿瘤细胞生长和肺转移,从而与骨肉瘤患者的不良预后相关,这表明SATB2-AS1和SATB2可能是风险分层的新型生物标志物以及骨肉瘤有前景的治疗靶点。