Ding Lei, Liu Taiyuan, Qu Yuan, Kang Zhichen, Guo Lixin, Zhang Haina, Jiang Junjie, Qu Fuling, Ge Wanbao, Zhang Shanyong
Department of Rehabilitation, The Second Hospital of Jilin University, Changchun 130000, Jilin, China.
Department of Breast Surgery, The Second Hospital of Jilin University, Changchun 130000, Jilin, China.
Mol Ther Nucleic Acids. 2021 Aug 26;26:787-797. doi: 10.1016/j.omtn.2021.08.022. eCollection 2021 Dec 3.
Osteosarcoma is a highly aggressive cancer common in children and adolescents. There is still a lack of effective treatments for metastatic or recurrent osteosarcoma. The role of long non-coding RNAs (lncRNAs) in osteosarcoma has gradually attracted attention. Here, we identified lncRNAs that were abnormally expressed in metastatic osteosarcoma through analyzing the sequencing data of osteosarcoma tissues and selected upregulated lncRNA MELTF-AS1 for detailed study. The qRT-PCR analysis showed that the expression of MELTF-AS1 was increased in osteosarcoma tissues and cells, and the high expression of MELTF-AS1 indicated a poor prognosis of osteosarcoma patients. The high expression of MELTF-AS1 in osteosarcoma was partly due to the transcriptional activation of RREB1. The results of transwell assays, scratch wound healing assays, and the tail vein injection lung metastasis model demonstrated that knocking down MELTF-AS1 inhibited metastasis ability of osteosarcoma cells. Furthermore, the results of RNA pull-down assays, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays revealed that MELTF-AS1 could regulate MMP14 expression through interaction with miR-485-5p. Our study suggested that MELTF-AS1 functioned as a pro-metastasis gene in osteosarcoma by upregulating MMP14 and that it could be a potential therapeutic and diagnostic target for osteosarcoma.
骨肉瘤是一种在儿童和青少年中常见的侵袭性很强的癌症。对于转移性或复发性骨肉瘤，仍然缺乏有效的治疗方法。长链非编码RNA（lncRNA）在骨肉瘤中的作用逐渐受到关注。在此，我们通过分析骨肉瘤组织的测序数据，鉴定出在转移性骨肉瘤中异常表达的lncRNA，并选择上调的lncRNA MELTF-AS1进行详细研究。qRT-PCR分析表明，MELTF-AS1在骨肉瘤组织和细胞中的表达增加，MELTF-AS1的高表达表明骨肉瘤患者预后不良。骨肉瘤中MELTF-AS1的高表达部分归因于RREB1的转录激活。Transwell实验、划痕伤口愈合实验和尾静脉注射肺转移模型的结果表明，敲低MELTF-AS1可抑制骨肉瘤细胞的转移能力。此外，RNA下拉实验、荧光素酶报告基因实验和RNA免疫沉淀（RIP）实验的结果显示，MELTF-AS1可通过与miR-485-5p相互作用来调节MMP14的表达。我们的研究表明，MELTF-AS1通过上调MMP14在骨肉瘤中发挥促转移基因的作用，并且它可能是骨肉瘤潜在的治疗和诊断靶点。
