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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
miR‑497/MIR497HG inhibits glioma cell proliferation by targeting CCNE1 and the miR‑588/TUSC1 axis
Li-Ya Ji1, Ming Wei2, Yuan-Yuan Liu2
1Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China.
Abstract:
Emerging evidence has shown that microRNA (miR)‑497 serves pivotal roles in tumorigenesis, cancer progression, metastasis and chemotherapy resistance in several types of cancer. In the present study, the expression and biological functions of miR‑497 host gene (MIR497HG) were investigated in glioma tissue. The expression levels of miR‑497 and MIR497HG were measured in glioma, adjacent non‑cancerous and normal brain tissue and their association with the prognosis of patients with glioma were analyzed. The biological roles of miR‑497 and MIR497HG were investigated in glioma cell lines. In addition, bioinformatics analysis, luciferase reporter assay and functional experiments were performed to identify and validate the downstream targets of miR‑497 or MIR497HG. The expression levels of miR‑497 and MIR497HG were downregulated in glioma tissue and cell lines compared with those in adjacent non‑cancerous and normal brain tissue and normal human cortical neuron cell line. Patients with low miR‑497 or MIR497HG expression levels exhibited a poor prognostic outcome. In addition, forced overexpression of miR‑497 or MIR497HG significantly inhibited the proliferation and cell cycle progression of glioma cell lines. Furthermore, the results indicated that miR‑497 and MIR497HG exerted their biological functions by direct targeting of cyclin E1 and miR‑588/tumor suppressor candidate 1. In summary, the data indicated that miR‑497 and MIR497HG served as tumor suppressors and may be used as potential therapeutic targets and prognostic biomarkers in glioma.
Insights
MicroRNA-497 and its host gene MIR497HG are downregulated in glioma, acting as tumor suppressors. Low expression correlates with poor prognosis, suggesting their potential as therapeutic targets and biomarkers for glioma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-497 (miR-497) is implicated in various cancers, affecting tumorigenesis, progression, metastasis, and chemotherapy resistance.
- The role and expression of the miR-497 host gene (MIR497HG) in glioma remain largely unexplored.
Purpose of the Study:
- To investigate the expression patterns and biological functions of miR-497 and MIR497HG in glioma.
- To determine the association between miR-497/MIR497HG expression and patient prognosis.
- To identify downstream targets and elucidate the underlying mechanisms of miR-497/MIR497HG in glioma.
Main Methods:
- Quantitative analysis of miR-497 and MIR497HG expression in glioma tissues and cell lines.
- Bioinformatics analysis, luciferase reporter assays, and functional experiments (e.g., cell proliferation, cell cycle assays).
- Correlation analysis between gene expression levels and patient survival data.
Main Results:
- miR-497 and MIR497HG were significantly downregulated in glioma tissues and cell lines compared to normal controls.
- Lower expression levels of miR-497 or MIR497HG were associated with poorer prognostic outcomes in glioma patients.
- Overexpression of miR-497 or MIR497HG suppressed glioma cell proliferation and cell cycle progression.
- miR-497 and MIR497HG directly target cyclin E1 and miR-588/tumor suppressor candidate 1.
Conclusions:
- miR-497 and MIR497HG function as tumor suppressors in glioma.
- These molecules represent potential therapeutic targets and prognostic biomarkers for glioma management.
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