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Long Non-coding RNA MINCR Regulates miR-876-5p/GSPT1 Axis to Aggravate Glioma Progression
Zheng Li1, Xiaoxia Xie2, Xiangyun Fan3
1Department of Neurosurgery, Deyang People's Hospital, Deyang, 618000, Sichuan, China.
Abstract:
Emerging evidence underlined the crucial roles played by long non-coding RNAs (lncRNAs) in glioma. MINCR has been reported in multiple malignancies. Here, we studied its function and potential mechanism in glioma, which remain unclear. Gene expressions were analyzed by qRT-PCR assay. Both in vitro and in vivo assays were conducted to evaluate the cellular function of MINCR in glioma. The subcellular situation of MINCR was detected by subcellular fractionation and FISH assays. Luciferase reporter, RNA pull-down and RNA immunoprecipitation (RIP) assays were combined to investigate potential mechanisms of relevant genes. MINCR was up-regulated in glioma. MINCR depletion markedly refrained glioma cell proliferation, migration and invasion via sponging miR-876-5p. MiR-876-5p suppressed the malignant behaviors of glioma via binding to GSPT1. MINCR shared the binding sites with the 3'-untranslated region of GSPT1 and prevented the binding of miR-876-5p to GSPT1 mRNA, thus up-regulating the level of GSPT1. Moreover, miR-876 inhibition and GSPT1 up-regulation counteracted the functional effect induced by silencing MINCR on glioma progression. Our findings uncovered that MINCR might aggravated glioma cell proliferation and migration via acting as competing endogenous RNA (ceRNA), indicating prospective novel therapeutic target for glioma.
Insights
Long non-coding RNA MINCR promotes glioma progression by sponging miR-876-5p and up-regulating GSPT1. Silencing MINCR inhibits glioma cell proliferation and migration, suggesting MINCR as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play critical roles in glioma development.
- The specific function and mechanism of lncRNA MINCR in glioma are not well understood.
Purpose of the Study:
- To investigate the role and underlying mechanism of MINCR in glioma.
- To explore MINCR as a potential therapeutic target for glioma.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for gene expression analysis.
- In vitro and in vivo assays to assess cellular functions.
- Subcellular fractionation and Fluorescence in situ hybridization (FISH) for localization.
- Luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays for mechanism investigation.
Main Results:
- MINCR was found to be significantly up-regulated in glioma tissues.
- Depletion of MINCR inhibited glioma cell proliferation, migration, and invasion.
- MINCR functions as a competing endogenous RNA (ceRNA) by sponging miR-876-5p, which in turn targets GSPT1.
- Restoring miR-876 inhibition or GSPT1 up-regulation reversed the effects of MINCR depletion.
Conclusions:
- MINCR exacerbates glioma cell proliferation and migration through the ceRNA mechanism involving miR-876-5p and GSPT1.
- MINCR represents a promising novel therapeutic target for glioma treatment.
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