<p>LncRNA GAS5 Regulates Osteosarcoma Cell Proliferation, Migration, and Invasion by Regulating RHOB via Sponging miR-663a</p>

Abstract

Introduction Emerging evidence has revealed the importance of long non-coding RNAs (lncRNAs) in carcinogenesis. The aim of this work was to investigate the roles of lncRNA growth arrest specific 5 (GAS5) in osteosarcoma (OS) progression. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to explore GAS5, microRNA-663a (miR-663a), and ras homolog family member B (RHOB) expression levels in OS tissues and cells. Moreover, cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were conducted to investigate biological roles of GAS5 in OS progression. In addition, mechanisms underlying the functions of GAS5 in OS were investigated by bioinformatic analysis, luciferase activity reporter assay, and rescue experiments. Results The GAS5 expression level was significantly decreased in OS tissues and cells compared with normal tissues and cells, and could negatively regulate miR-663a expression. Moreover, we found RHOB expression can be negatively regulated by miR-663a. Overexpression of GAS5 and RHOB suppresses, while overexpression of miR-663a stimulates, OS cell proliferation, migration, and invasion in vitro. In summary, we revealed lncRNA GAS5 was a downregulated lncRNA in OS and impaired OS malignant behaviors. In addition, this regulation relied on miR-663a and its target gene, RHOB. Discussion To sum up, we showed lncRNA GAS5 regulates OS progression via regulating the miR-663a/RHOB axis.

Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas

“…Such sponging of miR-21 was found to be much more than all the miRNAs tested. Some of the tested miRNAs have previously been shown to be targeted by GAS5 in osteosarcoma, such as miR-221 (Ye et al, 2017), miR-203a (Wang andKong, 2018), miR-23a (Liu et al, 2020), and miR-663a (Yao et al, 2020;Zhao et al, 2020). Our analysis thus yielded novel information on the miRNA that could be targeted by GAS5.…”

The Involvement of Long Non-Coding RNAs in Bone

“…Ye et al have also reported that GAS5 could suppress cell growth, migration, and epithelialmesenchymal transition (EMT) in OS by modulating the miR-221/aplasia Ras homolog member I (ARHI) axis [88]. At the same time, Yao et al observed that GAS5 could also stimulate OS progression suppressing Ras Homolog Family Member B (RHOB) expression through sponging miR-663a [89].…”

RHO GTPase-Related Long Noncoding RNAs in Human Cancers

“…As critical gene regulators, lncRNAs interact with DNA, RNA, and proteins to modulate gene expression at the pretranscriptional, transcriptional, and posttranscriptional levels [ 48 , 49 , 50 , 51 ]. In this regard, the associations between lncRNA and the regulatory machinery of chromatin remodeling, transcription, splicing, and nuclear trafficking clarify the details of the regulatory aspects of these RNA species [ 52 , 53 , 54 ]. lncRNAs act as competing endogenous RNAs (ceRNAs) to regulate other RNA transcripts by competing for shared miRNAs [ 52 , 55 ].…”

“…According to the dysregulation of many miRNAs in RHO GTPase-dependent malignancies, lncRNAs are, as negative regulators of miRNAs, likely to become a focus in the future development of new RHO GTPase-based therapies [ 56 ]. Significantly, recent studies have reported that lncRNAs and members of RHO GTPase signaling cascades are dysregulated in various human cancers ( Figure 2 ) [ 53 , 54 ].…”

“…Furthermore, the capacity of GAS5 to bind to other oncogenic miRNAs confirms the pivotal role of this lncRNA in the modulation of different cancer-related genes [ 130 , 131 , 132 ]. Strikingly, regulation of RHOB by GAS5 illustrates the ability of this RNA molecule to be a modulator of the RHO GTPase family [ 53 ]. It was discovered that miR-663a expression was remarkably elevated in both tissues and plasmas of osteosarcoma patients [ 133 ].…”