Fei Dan, Zhang Xiaona, Lu Yang, Tan Long, Xu Mingzhu, Zhang Yang
Department of Ultrasonographic, The Third Hospital of Jilin University Changchun 130033, P. R. China.
Department of Anesthesiology, The First Hospital of Jilin University Changchun 130021, P. R. China.
Am J Transl Res. 2020 May 15;12(5):2155-2168. eCollection 2020.
Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been reported to be involved in the progression of multiple cancers. However, exact function and regulatory mechanism of AFAP1-AS1 in osteosarcoma (OS) remain largely unclear. In this study, quantitative real time polymerase chain reaction (qRT-PCR) revealed that AFAP1-AS1 was upregulated in OS tissues and cell lines. Increased AFAP1-AS1 was associated with poor prognosis. Loss-of-function experiments demonstrated that knockdown of AFAP1-AS1 inhibited the proliferation, colony formation, migration, invasion and induced cell apoptosis. Bioinformatics analysis and luciferase reporter assays confirmed that mircoRNA-497 (miR-497) was a directly target of AFAP1-AS1. Rescue experiments confirmed that miR-497 inhibition could partially reverse the inhibitory effect of AFAP1-AS1 knockdown on OS cells. Moreover, AFAP1-AS1 modulated the expression of insulin-like growth factor 1 receptor (IGF1R, a target of miR-497) indirectly. xenograft tumor assay showed that AFAP1-AS1 knockdown inhibited tumor tumorigenesis. Taken together, these findings indicate that AFAP1-AS1 promotes OS progression by regulating miR-497/IGF1R axis, providing a therapeutic target for OS.
长链非编码RNA（lncRNA）肌动蛋白丝相关蛋白1反义RNA 1（AFAP1-AS1）已被报道参与多种癌症的进展。然而，AFAP1-AS1在骨肉瘤（OS）中的具体功能和调控机制仍不清楚。在本研究中，定量实时聚合酶链反应（qRT-PCR）显示AFAP1-AS1在OS组织和细胞系中上调。AFAP1-AS1升高与预后不良相关。功能丧失实验表明，敲低AFAP1-AS1可抑制增殖、集落形成、迁移、侵袭并诱导细胞凋亡。生物信息学分析和荧光素酶报告基因检测证实，微小RNA-497（miR-497）是AFAP1-AS1的直接靶点。挽救实验证实，抑制miR-497可部分逆转敲低AFAP1-AS1对OS细胞的抑制作用。此外，AFAP1-AS1间接调节胰岛素样生长因子1受体（IGF1R，miR-497的一个靶点）的表达。异种移植瘤实验表明，敲低AFAP1-AS1可抑制肿瘤发生。综上所述，这些发现表明AFAP1-AS1通过调节miR-497/IGF1R轴促进OS进展，为OS提供了一个治疗靶点。
