长链非编码 RNA ASMTL-AS1 通过诱饵 microRNA-342-3p 从而提高 ADAM9 表达来恶化骨肉瘤的致癌性。

Long non-coding RNA ASMTL-AS1 deteriorates the oncogenicity of osteosarcoma by decoying microRNA-342-3p and consequently raising ADAM9 expression.

机构信息

Department of Hand, Foot and Ankle Surgery, Zaozhuang Municipal Hospital, Shandong, 277100, China.

Medical College, Zaozhuang Vocational College, Shandong, 277800, China.

出版信息

Biochem Biophys Res Commun. 2021 Nov 19;579:89-96. doi: 10.1016/j.bbrc.2021.09.049. Epub 2021 Sep 22.

DOI:10.1016/j.bbrc.2021.09.049

PMID:34597997

Abstract

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.

摘要

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 ASMTL-AS1 缺失在 OS 细胞中的调控作用。利用生物信息学分析、荧光素酶报告基因检测、RNA 免疫沉淀和挽救实验进行机制研究。

结果

TCGA 数据库和我们自己的队列均显示 OS 中 ASMTL-AS1 的表达升高。干扰 ASMTL-AS1 可抑制体外细胞增殖、迁移和侵袭，增加细胞凋亡。此外，沉默 ASMTL-AS1 可抑制体内肿瘤生长。机制上，ASMTL-AS1 可作为 microRNA-342-3p（miR-342-3p）的竞争性内源性 RNA，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）水平升高。此外，抑制 miR-342-3p 或上调 ADAM9 可减弱沉默 ASMTL-AS1 诱导的 OS 细胞抗肿瘤活性。