Department of Orthopaedics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, PR China.
Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, PR China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):260-266. doi: 10.1016/j.bbrc.2018.11.019. Epub 2018 Nov 13.
Osteosarcoma is the most common primary bone tumor and occurs most frequently in adolescents. Cancer stem cells (CSCs) are resistant to chemotherapy and radiotherapy, and can drive cancer recurrence. In this study, we aimed to investigate the effect of Long noncoding RNAs (lncRNAs) DLX6-AS1 on osteosarcoma stemness and the underlying mechanism involved. DLX6-AS1 enhanced osteosarcoma stemness in vitro and in vivo. Moreover, DLX6-AS1 competitively interacted with miR-129-5p to DLK1, resulting in activation of Wnt signaling and promotion of stemness in osteosarcoma. DLX6-AS1 functionally interplayed with miR-129-5p to form a reciprocal feedback loop to activate Wnt signaling. High DLX6-AS1 expression was observed in osteosarcoma tissues, and predicted a poor prognosis for osteosarcoma patients. Our study suggests that DLX6-AS1, combined with miR-129-5p and DLK1, can be utilized as factors for the clinical diagnosis and prognosis of osteosarcoma, and may be potential targets for the treatment of osteosarcoma.
成骨肉瘤是最常见的原发性骨肿瘤,多见于青少年。癌症干细胞(CSCs)对化疗和放疗具有抗性,并可导致癌症复发。在本研究中,我们旨在研究长非编码 RNA(lncRNA)DLX6-AS1 对成骨肉瘤干细胞特性的影响及其涉及的潜在机制。DLX6-AS1 增强了成骨肉瘤的体外和体内干细胞特性。此外,DLX6-AS1 与 miR-129-5p 竞争性相互作用于 DLK1,导致 Wnt 信号通路的激活,并促进成骨肉瘤的干细胞特性。DLX6-AS1 与 miR-129-5p 具有功能相互作用,形成一个相互反馈回路以激活 Wnt 信号通路。在成骨肉瘤组织中观察到高表达的 DLX6-AS1,并且预示着成骨肉瘤患者的预后不良。我们的研究表明,DLX6-AS1 与 miR-129-5p 和 DLK1 结合,可以作为成骨肉瘤临床诊断和预后的指标,并可能成为成骨肉瘤治疗的潜在靶点。