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Author Spotlight: RNA FISH for Locating lncRNA-SNHG6 in Osteosarcoma Cells
Published on: June 16, 2023
LncRNA LBX2-AS1 impacts osteosarcoma sensitivity to JQ-1 by sequestering miR-597-3p away from BRD4
Jiayu Li1,2, Xuhui Yuan1,2, Cong Ma3
1Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Central Laboratory, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Objective:
Recent knowledge concerning the significance of long non-coding RNA (lncRNA)-mediated ceRNA networks provides new insight into their possible roles as specific biomarkers for the treatment of osteosarcoma (OS). Thus, this study aims to clarify the functional relevance and mechanistic actions of lncRNA LBX2-AS1 in OS.
Methods:
Differential analysis was performed by integrating the TCGA and GTEx databases. Cox regression analysis was then employed to assess the prognostic value of the model. The expression of lncRNA LBX2-AS1 and miR-597-3p was quantified in OS cell lines by qRT-PCR. The proliferation, migration, invasion, and apoptosis of OS cell lines in response to manipulated lncRNA LBX2-AS1 were evaluated by MTT, colony formation, transwell, Western blot, and flow cytometry assays. Luciferase activity was assayed to validate the reciprocal regulation between lncRNA LBX2-AS1 and miR-597-3p. The protein levels of BRD4 and EMT-related factors were examined by Western blot assay. Finally, tumor growth in response to LBX2-AS1 knockdown was evaluated in xenograft-bearing nude mice.
Results:
By integrating the GTEx and TCGA databases, we identified 153 differentially expressed lncRNAs. Among them, 5 lncRNAs, RP11-535M15.1, AC002398.12, RP3-355L5.4, LBX2-AS1, and RP11.47A8.5, were selected to establish a model, which predicted the prognosis of OS. Higher lncRNA LBX2-AS1 expression was noted in OS tissues relative to that in normal tissues. Silencing lncRNA LBX2-AS1 facilitated apoptosis and curtailed proliferative, migratory, and invasive capacities of OS cells. Mechanistically, lncRNA LBX2-AS1 could elevate the expression of BRD4, an oncogene, by competitively binding to miR-597-3p. More importantly, knockdown of lncRNA LBX2-AS1 increased the sensitivity of OS cells to the BRD4 inhibitor JQ-1. Finally, the tumor growth of OS cell xenografts was constrained in vivo in the presence of lncRNA LBX2-AS1 knockdown.
Conclusion:
In conclusion, lncRNA LBX2-AS1 promotes the growth of OS and represses the sensitivity to JQ-1 by sponging miR-597-3p to elevate the expression of BRD4.
Insights
Long non-coding RNA LBX2-AS1 promotes osteosarcoma growth by sponging miR-597-3p and elevating BRD4. Knockdown of LBX2-AS1 inhibits tumor growth and enhances sensitivity to JQ-1 in osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
- ceRNA networks involving lncRNAs offer potential biomarkers for osteosarcoma (OS) treatment.
- Understanding the specific functions of lncRNAs like LBX2-AS1 in OS is crucial.
Purpose of the Study:
- To investigate the functional significance of lncRNA LBX2-AS1 in osteosarcoma.
- To elucidate the underlying molecular mechanisms of LBX2-AS1 in OS progression.
- To assess the potential of LBX2-AS1 as a therapeutic target in OS.
Main Methods:
- Differential expression analysis using TCGA and GTEx databases.
- Prognostic value assessment via Cox regression.
- In vitro assays (qRT-PCR, MTT, colony formation, transwell, Western blot, flow cytometry) to evaluate OS cell behavior.
- Luciferase assays to confirm interactions.
- In vivo xenograft mouse models to assess tumor growth.
Main Results:
- LBX2-AS1 was identified as a key lncRNA in a prognostic model for OS.
- Higher LBX2-AS1 expression correlated with OS tissues.
- Silencing LBX2-AS1 inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis.
- LBX2-AS1 upregulates the oncogene BRD4 by sponging miR-597-3p.
- Knockdown of LBX2-AS1 increased OS cell sensitivity to the BRD4 inhibitor JQ-1.
- LBX2-AS1 knockdown suppressed tumor growth in vivo.
Conclusions:
- lncRNA LBX2-AS1 promotes osteosarcoma progression.
- LBX2-AS1 acts as a molecular sponge for miR-597-3p, leading to increased BRD4 expression.
- Targeting LBX2-AS1 may be a viable strategy to enhance the efficacy of BRD4 inhibitors like JQ-1 in osteosarcoma treatment.
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