Xu Yining, Yao Teng, Huang Kangmao, Liu Gang, Huang Yizhen, Gao Jun, Ye Huali, Shen Shuying, Ma Jianjun
Shaoxing University School of Medicine, Shaoxing, Zhejiang 312000, People's Republic of China.
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China.
Onco Targets Ther. 2020 May 4;13:3729-3737. doi: 10.2147/OTT.S245366. eCollection 2020.
Prevailing evidences have demonstrated that circular RNAs (circRNAs) are closely associated with various stages of carcinogenesis. However, very few studies have delineated the specific mechanism of association between circRNAs and osteosarcoma (OS). It offers a novel insight that circRNAs can be explored as a potential therapeutic strategy for OS.
In this study, circTUBGCP3 was chosen from the existing reported circRNA microarray data obtained from OS cell lines and normal bone cells. Subsequently, qRT-PCR was performed to evaluate the expression level of circTUBGCP3 in OS samples and cell lines. Functional assays were conducted to estimate the impact of circTUBGCP3 on human OS cells proliferation, vitality, survivability, and migration. Western blot, luciferase reporter and in vivo tumorigenesis assays were performed to analyze the signaling pathways underlying the interaction of circTUBGCP3, miR-30b, and Vimentin.
The data indicate that circTUBGCP3 may act as a sponge of miR-30b that further alters the expression of Vimentin, and promotes the proliferation and metastatic properties of OS cells.
circTUBGCP3 serves as a tumor promoter in tumorigenesis by increasing the possibilities of OS initiation and proliferation.
现有证据表明,环状RNA(circRNA)与癌症发生的各个阶段密切相关。然而,很少有研究阐明circRNA与骨肉瘤(OS)之间关联的具体机制。这为将circRNA作为OS的潜在治疗策略进行探索提供了新的见解。
在本研究中,circTUBGCP3是从现有的已报道的骨肉瘤细胞系和正常骨细胞的circRNA微阵列数据中选取的。随后,进行qRT-PCR以评估circTUBGCP3在骨肉瘤样本和细胞系中的表达水平。进行功能测定以评估circTUBGCP3对人骨肉瘤细胞增殖、活力、生存能力和迁移的影响。进行蛋白质免疫印迹、荧光素酶报告基因和体内肿瘤发生试验,以分析circTUBGCP3、miR-30b和波形蛋白相互作用的信号通路。
数据表明,circTUBGCP3可能作为miR-30b的海绵,进而改变波形蛋白的表达,并促进骨肉瘤细胞的增殖和转移特性。
circTUBGCP3通过增加骨肉瘤起始和增殖的可能性,在肿瘤发生中作为肿瘤促进因子发挥作用。