Cao Kun, Fang Yueyang, Wang Hao, Jiang Zheng, Guo Li, Hu Yong
Department of Orthopaedics, The First Hospital Of Anhui Medical University, Hefei, People's Republic of China.
Department of Orthopaedics, The Second Hospital Of Shanxi Medical University, Taiyuan, People's Republic of China.
Cancer Manag Res. 2019 May 16;11:4505-4518. doi: 10.2147/CMAR.S196025. eCollection 2019.
Many studies have shown that long non-coding RNAs (lncRNAs) are closely related to various cancers. This study aims to explore the roles of lncRNA HOXA11-AS in the development and progression of osteosarcoma (OS). The expression levels of HOXA11-AS and miR-125a-5p in tumor tissues and the adjacent tissues were detected by RT-PCR method. The proliferation, migration and invasion of MG-63 and KHOS cells were determined. It was found that HOXA11-AS expression levels in OS tissues and OS cell lines were higher than those in OS adjacent tissues and normal human osteoblast cell lines. The higher expression level of HOXA11-AS was positively correlated with more severe clinical stage, distant metastasis and poor prognosis of OS. Inhibition of HOXA11-AS expression could reduce metastasis and invasion of OS cell lines. In addition, HOXA11-AS was found to be an endogenous inhibitor of miR-125a-5p, it down regulated the expression level of miR-125a-5p, and this process could promote the expression of Rab3D, the target gene of miR-125a-5p. Our study elucidated the role of a new HOXA11-AS/miR-125a-5p/Rab3D regulatory pathway in promoting OS metastasis.
许多研究表明，长链非编码RNA（lncRNA）与多种癌症密切相关。本研究旨在探讨lncRNA HOXA11-AS在骨肉瘤（OS）发生发展及进展中的作用。采用RT-PCR法检测肿瘤组织及癌旁组织中HOXA11-AS和miR-125a-5p的表达水平。检测MG-63和KHOS细胞的增殖、迁移和侵袭能力。结果发现，OS组织和OS细胞系中HOXA11-AS的表达水平高于OS癌旁组织和正常人成骨细胞系。HOXA11-AS的高表达水平与OS更严重的临床分期、远处转移及预后不良呈正相关。抑制HOXA11-AS的表达可降低OS细胞系的转移和侵袭能力。此外，发现HOXA11-AS是miR-125a-5p的内源性抑制剂，它下调miR-125a-5p的表达水平，且该过程可促进miR-125a-5p的靶基因Rab3D的表达。我们的研究阐明了一种新的HOXA11-AS/miR-125a-5p/Rab3D调控通路在促进OS转移中的作用。
