Background

Till now, little is known regarding expression pattern and specific roles of lncRNA ASMTL antisense RNA 1 (ASMTL-AS1) in osteosarcoma (OS). Therefore, our current research measured the expression of ASMTL-AS1 in OS, unveiled the roles of ASMTL-AS1 in the modulation of malignant characteristics of OS, and identified the downstream mechanism.

Methods

The regulatory actions of ASMTL-AS1 ablation in OS cells were explored utilizing loss-of-function experiments. Mechanistic studies were implemented utilizing bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation and rescue experiments.

Results

ASMTL-AS1 expression in OS was elevated in both TCGA database and our own cohort. Interfering with ASMTL-AS1 restricted cell proliferation, migration and invasion while increasing cell apoptosis in vitro. Additionally, silencing ASMTL-AS1 blocked tumour growth in vivo. Mechanistically, ASMTL-AS1 could act as a competing endogenous RNA for microRNA-342–3p (miR-342–3p) and inhibit its activity in OS cells, consequently causing an increase in ADAM metallopeptidase domain 9 (ADAM9) levels. Furthermore, inhibiting miR-342–3p or upregulating ADAM9 abated silenced ASMTL-AS1-induced antitumour activity in OS cells.

Conclusion

ASMTL-AS1 aggravated OS progression by regulating the miR-342–3p/ADAM9 axis.

中文翻译：

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长链非编码 RNA ASMTL-AS1 通过诱骗 microRNA-342-3p 从而提高 ADAM9 表达来降低骨肉瘤的致癌性

背景

到目前为止，关于 lncRNA ASMTL 反义 RNA 1 (ASMTL-AS1) 在骨肉瘤 (OS) 中的表达模式和具体作用知之甚少。因此，我们目前的研究测量了 ASMTL-AS1 在 OS 中的表达，揭示了 ASMTL-AS1 在调节 OS 恶性特征中的作用，并确定了下游机制。

方法

利用功能丧失实验探索了 OS 细胞中 ASMTL-AS1 消融的调节作用。利用生物信息学分析、荧光素酶报告基因测定、RNA 免疫沉淀和救援实验实施了机制研究。

结果

在 TCGA 数据库和我们自己的队列中，OS 中的 ASMTL-AS1 表达均升高。干扰 ASMTL-AS1 限制细胞增殖、迁移和侵袭，同时增加体外细胞凋亡。此外，沉默 ASMTL-AS1 可阻止体内肿瘤生长。从机制上讲，ASMTL-AS1 可以作为 microRNA-342-3p (miR-342-3p) 的竞争性内源 RNA 并抑制其在 OS 细胞中的活性，从而导致 ADAM 金属肽酶结构域 9 (ADAM9) 水平的增加。此外，抑制 miR-342-3p 或上调 ADAM9 减弱了 OS 细胞中沉默的 ASMTL-AS1 诱导的抗肿瘤活性。

结论

ASMTL-AS1 通过调节 miR-342-3p/ADAM9 轴加重 OS 进展。