Department of Hand, Foot and Ankle Surgery, Zaozhuang Municipal Hospital, Shandong, 277100, China.
Medical College, Zaozhuang Vocational College, Shandong, 277800, China.
Biochem Biophys Res Commun. 2021 Nov 19;579:89-96. doi: 10.1016/j.bbrc.2021.09.049. Epub 2021 Sep 22.
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.
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.
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.
ASMTL-AS1 aggravated OS progression by regulating the miR-342-3p/ADAM9 axis.
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。
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。
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。
ASMTL-AS1 通过调节 miR-342-3p/ADAM9 轴加重 OS 进展。
