He Jia-Wen, Li De-Jian, Zhou Jian-Hua, Zhu Ya-Long, Yu Bao-Qing
Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai, China.
Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai, China.
Biochem Biophys Res Commun. 2020 Jun 4;526(3):670-677. doi: 10.1016/j.bbrc.2020.03.151. Epub 2020 Apr 2.
Growing studies have indicated the involvements of long noncoding RNAs (lncRNAs) in the initiation and progression of various tumors. We aimed to investigated the role of lncRNA LMCD1 antisense RNA 1 (LMCD1-AS1) in osteosarcoma development. We found that LMCD1-AS1 and SP1 were highly expressed in osteosarcoma tissues and cell lines. High levels of LMCD1-AS1 were correlated with positively metastasis and poor clinical prognosis. Moreover, we showed that SP1 can bind to the promoter region of LMCD1-AS1, resulting in its overexpression in osteosarcoma. Functionally, silencing of LMCD1-AS1 suppressed the proliferation, migration, invasion and EMT progress of osteosarcoma cells. Mechanistic studies revealed that LMCD1-AS1 was a sponge of miR-106b-5p activity. LMCD1-AS1 modulated survival of osteosarcoma via targeting miR-106b-5p. Overall, we firstly indicated that LMCD1-AS1 overexpression contributes to osteosarcoma development and poor clinical outcome, suggesting that LMCD1-AS1 may be a novel diagnostic and prognostic biomarker for osteosarcoma and a target for osteosarcoma therapy.
越来越多的研究表明，长链非编码RNA（lncRNA）参与了各种肿瘤的发生和发展。我们旨在研究lncRNA LMCD1反义RNA 1（LMCD1-AS1）在骨肉瘤发生中的作用。我们发现LMCD1-AS1和SP1在骨肉瘤组织和细胞系中高表达。高水平的LMCD1-AS1与骨肉瘤的转移和不良临床预后呈正相关。此外，我们发现SP1可以结合到LMCD1-AS1的启动子区域，导致其在骨肉瘤中过表达。在功能上，沉默LMCD1-AS1可抑制骨肉瘤细胞的增殖、迁移、侵袭和上皮-间质转化进程。机制研究表明，LMCD1-AS1是miR-106b-5p活性的海绵。LMCD1-AS1通过靶向miR-106b-5p调节骨肉瘤的生存。总体而言，我们首次表明LMCD1-AS1的过表达促进了骨肉瘤的发生和不良临床结局，提示LMCD1-AS1可能是骨肉瘤的一种新型诊断和预后生物标志物以及骨肉瘤治疗的靶点。
