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Long Noncoding RNA XIST Promotes Osteosarcoma Progression by Targeting Ras-Related Protein RAP2B via miR-320b
Gong-Yi Lv1, Jun Miao1, Xiao-Lin Zhang1
1Department of Spinal Surgery, Tianjin Hospital, Tianjin, P.R. China.
Abstract:
Abnormal expression of long noncoding RNAs (lncRNAs) often contributes to the unrestricted growth and invasion of cancer cells. lncRNA X-inactive specific transcript (XIST) expression is upregulated in several cancers; however, its underlying mechanism in osteosarcoma (OS) has not been elucidated. In the present study, we found that XIST expression was significantly increased in OS tissues and cell lines by LncRNA Profiler and qRT-PCR. The effects of XIST and miR-320b on OS cell proliferation and invasion were studied by MTT and Transwell invasion assays. The competing relationship between XIST and miR-320b was confirmed by luciferase reporter assay. Our results showed that XIST knockdown strikingly inhibited cell proliferation and invasion. Furthermore, XIST could directly bind to miR-320b and repress miR-320b expression. Moreover, XIST overexpression significantly relieved the inhibition on OS cell proliferation and invasion mediated by miR-320b overexpression, which involved the derepression of Ras-related protein RAP2B. We propose that XIST is responsible for OS cell proliferation and invasion and that XIST exerts its function through the miR-320b/RAP2B axis. Our findings suggest that lncRNA XIST may be a candidate prognostic biomarker and a target for new therapies in OS patients.
Insights
Long noncoding RNA XIST promotes osteosarcoma progression by inhibiting miR-320b, leading to increased proliferation and invasion. Targeting XIST may offer new therapeutic strategies for osteosarcoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Abnormal long noncoding RNA (lncRNA) expression is linked to cancer progression.
- X-inactive specific transcript (XIST) is upregulated in various cancers, but its role in osteosarcoma (OS) remains unclear.
Purpose of the Study:
- To investigate the mechanism of lncRNA XIST in osteosarcoma (OS) cell proliferation and invasion.
- To explore the relationship between XIST, miR-320b, and RAP2B in OS.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and LncRNA Profiler to assess XIST expression.
- MTT and Transwell invasion assays to evaluate cell proliferation and invasion.
- Luciferase reporter assay to confirm the interaction between XIST and miR-320b.
Main Results:
- XIST expression was significantly elevated in OS tissues and cell lines.
- XIST knockdown inhibited OS cell proliferation and invasion.
- XIST directly targets and represses miR-320b, affecting the miR-320b/RAP2B axis.
Conclusions:
- XIST promotes osteosarcoma cell proliferation and invasion via the miR-320b/RAP2B pathway.
- lncRNA XIST is a potential prognostic biomarker and therapeutic target for osteosarcoma.