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Updated: Jul 14, 2025
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
[miRNA-128-3p inhibits malignant behavior of glioma cells by downregulating KLHDC8A expression]
Zhengtao Yu1, Jiameng Li1, Junwen Jiang1
1Department of Neurosurgery, Affiliated Haikou Hospital of Xiangya School of Central South University, Haikou 570208, China.
Objective:
To determine whether miRNA-128-3p regulates malignant biological behavior of glioma cells by targeting KLHDC8A.
Methods:
Dual-luciferase reporter assays, qRT-PCR and Western blotting were used to verify the targeting of miRNA-128-3p to KLHDC8A. Edu assay, flow cytometry, Transwell assay and would healing assay were used to determine the effects of changes in miRNA-128-3p and KLHDC8A expression levels on malignant behavior of glioma cells. Rescue experiment was carried out to verify that miRNA-128-3p regulated glioma cell proliferation, apoptosis, invasion and migration by targeting KLHDC8A.
Results:
The expression level of KLHDC8A was significantly increased in high-grade glioma tissue and was closely related to a poor survival outcome of the patients. Overexpression of KLHDC8A promoted glioma cell proliferation, migration and invasion, and miRNA-128-3p overexpression inhibited proliferative and metastatic capacities of glioma cells. Mechanistically, KLHDC8A expression was directly modulated by miRNA-128-3p, which, by targeting KLHDC8A, inhibited malignant behavior of glioma cells.
Conclusion:
Upregulation of miRNA-128-3p inhibits uncontrolled growth of glioma cells by negatively regulating KLHDC8A expression and its downstream effectors, suggesting that the miRNA-128-3p-KLHDC8A axis may serve as a potential prognostic indicator and a therapeutic target for developing new strategies for glioma treatment.
Insights
MicroRNA-128-3p (miRNA-128-3p) inhibits glioma cell growth and metastasis by targeting Kelch-like family domain containing 8A (KLHDC8A). This miRNA-KLHDC8A interaction offers a potential therapeutic target for glioma treatment.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Context:
- Glioma is a primary brain tumor with significant morbidity and mortality.
- Aberrant gene expression, including microRNAs and their targets, plays a crucial role in glioma pathogenesis.
- Understanding the molecular mechanisms underlying glioma progression is essential for developing effective therapies.
Purpose:
- To investigate the regulatory role of miRNA-128-3p in the malignant biological behavior of glioma cells.
- To determine if KLHDC8A is a direct target of miRNA-128-3p.
- To elucidate the therapeutic potential of the miRNA-128-3p-KLHDC8A axis in glioma.
Summary:
- KLHDC8A expression is elevated in high-grade glioma and correlates with poor patient survival.
- Overexpression of KLHDC8A promotes glioma cell proliferation, migration, and invasion.
- miRNA-128-3p directly targets KLHDC8A, inhibiting these malignant behaviors and suggesting a tumor-suppressive role.
Impact:
- Identifies a novel miRNA-KLHDC8A regulatory axis in glioma.
- Provides mechanistic insights into glioma cell proliferation and metastasis.
- Suggests that the miRNA-128-3p-KLHDC8A pathway could be a prognostic biomarker and therapeutic target for glioma.
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