Department of Spine Surgery of Traditonal Chinese Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830000, China.
Department of Spine Surgery of Traditonal Chinese Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830000, China.
Biomed Pharmacother. 2018 Oct;106:890-895. doi: 10.1016/j.biopha.2018.06.173. Epub 2018 Jul 12.
Osteosarcoma is the most common primary malignant bone tumor and long non-coding RNAs (lncRNAs) have been proved to epigenetically regulate the oncogenesis of osteosarcoma. In this research, we investigate the role of lncRNA HOXD-AS1 on the osteosarcoma oncogenesis. Results revealed that HOXD-AS1 expression level was significantly up-regulated in osteosarcoma tissue and cells, moreover, the aberrant overexpression predicted the poor prognosis of osteosarcoma patients. Loss-of-functional experiments indicated that HOXD-AS1 silencing inhibited the osteosarcoma cells proliferation and induced G1/G0 phase arrest in vitro, and repressed tumor cell growth in vivo. Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. Rescue experiments revealed that p57 could recover the oncogenic role of HOXD-AS1 on osteosarcoma. In conclusion, our study confirmed that HOXD-AS1 could interact with EZH2, and then repress p57 expression, to aggravate osteosarcoma oncogenesis. which provide new idea for the osteosarcoma tumorigenesis.
骨肉瘤是最常见的原发性恶性骨肿瘤，长链非编码 RNA（lncRNA）已被证明能通过表观遗传调控骨肉瘤的发生。在这项研究中，我们研究了 lncRNA HOXD-AS1 对骨肉瘤发生的作用。结果表明，HOXD-AS1 在骨肉瘤组织和细胞中的表达水平显著上调，此外，异常高表达预示着骨肉瘤患者预后不良。功能丧失实验表明，HOXD-AS1 沉默抑制骨肉瘤细胞增殖，并在体外诱导 G1/G0 期停滞，在体内抑制肿瘤细胞生长。机制研究表明，HOXD-AS1 通过招募增强子结合锌指蛋白 2（EZH2）到 p57 启动子上来表观遗传抑制 p57。挽救实验表明，p57 可以恢复 HOXD-AS1 对骨肉瘤的致癌作用。总之，我们的研究证实 HOXD-AS1 可以与 EZH2 相互作用，然后抑制 p57 的表达，从而加重骨肉瘤的发生。这为骨肉瘤的肿瘤发生提供了新的思路。
