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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
hsa_circ_0010889 downregulation inhibits malignant glioma progression by modulating the miR-590-5p/SATB1 axis
1Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, China.
Abstract:
Glioma is a general neurological tumor and circular RNAs (circRNAs) have been implicated in glioma development. However, the underlying mechanisms and circRNA biological functions responsible for the regulation of glioma progression remain unknown. In this study, we employ next-generation sequencing (NGS) to investigate altered circRNA expression in glioma tissues. Regulatory mechanisms were studied using luciferase reporter analyses, transwell migration, CCK8, and EdU analysis. Tumorigenesis and metastasis assays were utilized to determine the function of hsa_circ_0010889 in glioma. Our results showed that hsa_circ_0010889 expression increased in glioma cell lines and tissues, indicating that hsa_circ_0010889 may be involved in glioma progression. Downregulation of hsa_circ_0010889 inhibited glioma invasion and proliferation in both in vitro and in vivo experiments and luciferase report assays found that miR-590-5p and SATB1 were downstream targets for hsa_circ_0010889. SATB1 overexpression or miR-590-5p inhibition reversed glioma cells proliferation and migration post-silencing of hsa_circ_0010889. Taken together, our study demonstrates that hsa_circ_0010889 downregulation inhibits glioma progression through the miR-590-5p/SATB1 axis.
Insights
Circular RNAs (circRNAs) play a role in glioma. This study found that downregulating hsa_circ_0010889 inhibits glioma progression by targeting the miR-590-5p/SATB1 pathway.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genomics
Background:
- Glioma is a common brain tumor.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer, including glioma.
- The specific functions and regulatory mechanisms of circRNAs in glioma progression are not fully understood.
Purpose of the Study:
- To investigate the role of circRNAs in glioma development.
- To identify specific circRNAs involved in glioma progression.
- To elucidate the molecular mechanisms by which circRNAs regulate glioma.
Main Methods:
- Next-generation sequencing (NGS) to profile circRNA expression in glioma tissues.
- In vitro assays (luciferase reporter, Transwell migration, CCK8, EdU) to study regulatory mechanisms and cellular functions.
- In vivo tumorigenesis and metastasis assays to confirm the role of hsa_circ_0010889.
Main Results:
- hsa_circ_0010889 expression was significantly upregulated in glioma tissues and cell lines.
- Downregulation of hsa_circ_0010889 suppressed glioma cell proliferation, invasion, and metastasis in vitro and in vivo.
- Luciferase reporter assays identified miR-590-5p and SATB1 as direct downstream targets of hsa_circ_0010889.
Conclusions:
- hsa_circ_0010889 acts as an oncogenic circRNA in glioma.
- hsa_circ_0010889 promotes glioma progression by sponging miR-590-5p, leading to SATB1 upregulation.
- Targeting the hsa_circ_0010889/miR-590-5p/SATB1 axis represents a potential therapeutic strategy for glioma.
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