MIR205 host gene (MIR205HG) drives osteosarcoma metastasis via regulating the microRNA 2114-3p (miR-2114-3p)/twist family bHLH transcription factor 2 (TWIST2) axis

Abstract

Osteosarcoma (OS) is an aggressive malignant tumor with a high rate of lung metastasis and a lack of therapeutic targets. Although the anomalous expression of long non-coding RNA (lncRNA) has been extensively documented in human cancer, its contribution to OS metastasis remains poorly understood. In this study, we found that MIR205 host gene (MIR205HG) was significantly elevated in human OS tissues, especially in metastatic OS tissues. Stable knockdown of MIR205HG inhibited OS cell invasion and lung metastatic foci formation, but did not affect cell viability. The vast majority of MIR205HG was situated in the cytosol, and served as a competing endogenous RNA (ceRNA) that directly bound to microRNA 2114-3p (miR-2114-3p), resulting in increased twist family bHLH transcription factor 2 (TWIST2) level. Pre-clinically, high MIR205HG was linked with dismal overall and relapse-free survival. Functionally, the attenuated cell invasion caused by MIR205HG knockdown was effectively rescued by miR-2114-3p silencing or TWIST2 overexpression. Overall, our findings suggest that the previously uncharacterized regulatory axis of MIR205HG/miR-2114-3p/TWIST2 plays a critical role in promoting OS metastasis, which implies a potential therapeutic target in OS patients with metastasis.

RETRACTED ARTICLE: Long non-coding RNA taurine up regulated 1 promotes osteosarcoma cell proliferation and invasion through upregulating Ezrin expression as a competing endogenous RNA of micro RNA-377-3p

“…For instance, lncRNA MRPL23-AS1 promotes OS progression through inhibiting micro RNA (miRNA) miR-30b to enhance myosin heavy chain 9 (MYH9) expression and activate Wnt/β-catenin pathway [ 8 ]. Moreover, lncRNA MIR205 host gene (MIR205HG) enhances OS metastasis by miR-2114-3p/twist family bHLH transcription factor 2 (TWIST2) axis [ 9 ]. In addition, previous studies have demonstrated that lncRNA taurine upregulated 1 (TUG1) contributes to the proliferation and apoptosis of multiple tumor cells, which is a promising tumor therapeutic target.…”

LINC00467 Is Upregulated by DNA Copy Number Amplification and Hypomethylation and Shows ceRNA Potential in Lung Adenocarcinoma

“…According to the ceRNA hypothesis, lncRNAs can form a sponge with miRNAs to regulate the expression of target genes at the mRNA level (6). Recent studies have confirmed that ceRNAs have significant roles in cancer pathogenesis by altering the expression of key tumorigenic or tumor suppressive genes (6,(36)(37)(38). Two prior studies have investigated the ceRNA function of LIN00467 in LUAD (17,18).…”

Development of an Inflammation-Related lncRNA-miRNA-mRNA Network Based on Competing Endogenous RNA in Breast Cancer at Single-Cell Resolution

“…By combination of correlation analysis, expression analysis and survival analysis, miR-3127-5p and miR-2114-3p were selected as the two most potential downstream binding miRNAs of LRRC75A-AS1 in breast cancer. Both of the two miRNAs have been reported to be involved in initiation and progression of human malignancies, including osteosarcoma (Wang et al, 2021), papillary thyroid cancer (Zhou et al, 2021), colorectal cancer (Ma et al, 2021) and ovarian cancer (Yu Z et al, 2020).…”