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Published on: October 4, 2019
Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128-3p/SZRD1 axis in glioma
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Fengtai District, Beijing, China. liwei.zhang@ccmu.edu.cn.
Objective:
Long non-coding RNAs (lncRNAs) participate in multiple processes of malignant tumors, including glioma. In this study, we aimed to explore the effect of LINC00346 on glioma and its underlying mechanism.
Materials And Methods:
The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the expression patterns and survival risk of LINC00346, miR-128-3p and SUZ RNA binding domain containing 1 (SZRD1) in glioma tissues. The binding sites were predicted by bioinformatic databases, and then, validated by Dual-Luciferase assay and RNA immunoprecipitation (RIP). qRT-PCR and Western blot were performed to evaluate the gene expression levels. CellTiter-Glo® and colony formation assays were used to detect the proliferation of glioma cells. Flow cytometric analysis was used to evaluate the apoptosis of glioma cells. The xenograft models were established to investigate the impact of LINC00346 on tumor growth in vivo.
Results:
We found that both LINC00346 and SZRD1 expression were negatively related to the poor overall survival rate in glioma patients. However, miR-128-3p showed the opposite effect of survival outcomes. LINC00346 knockdown remarkably restrained cell proliferation both in vitro and in vivo, as well as inducing apoptosis by acting as a molecular sponge of miR-128-3p. Moreover, miR-128-3p bound to SZRD1 3'-UTR in a sequence-specific manner. In addition, LINC00346 knockdown significantly inhibited the expression of SZRD1 and the inhibition could be reversed by miR-128-3p mimics. Furthermore, cell proliferation and apoptosis affected by LINC00346 were partially rescued by modulating miR-128-3p or SZRD1 expression.
Conclusions:
LINC00346/miR-128-3p/SZRD1 axis played a crucial role in modulating the malignant progression of glioma, which may serve as a prognostic indicator and a probable therapeutic target for glioma.
Insights
Long non-coding RNA LINC00346 promotes glioma progression by sponging miR-128-3p, leading to increased SUZ12 expression. This axis impacts patient survival and offers potential therapeutic targets for glioma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are implicated in various cancer processes, including glioma.
- Understanding the specific roles of lncRNAs like LINC00346 in glioma is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of LINC00346 in glioma progression.
- To elucidate the underlying molecular mechanism involving miR-128-3p and SUZ12 (SZRD1).
Main Methods:
- Analysis of TCGA and CGGA databases for expression and survival data.
- Bioinformatic prediction, Dual-Luciferase assay, and RIP to validate interactions.
- qRT-PCR, Western blot, cell proliferation, apoptosis assays, and in vivo xenograft models.
Main Results:
- LINC00346 and SZRD1 expression correlated with poor glioma patient survival; miR-128-3p showed an opposite trend.
- LINC00346 knockdown inhibited glioma cell proliferation and induced apoptosis by sponging miR-128-3p.
- LINC00346 regulates SZRD1 expression via the miR-128-3p pathway, affecting tumor growth and apoptosis.
Conclusions:
- The LINC00346/miR-128-3p/SZRD1 axis is critical in glioma malignant progression.
- This axis represents a potential prognostic biomarker and therapeutic target for glioma.
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