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Updated: Nov 27, 2025
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
MiR-376a-3p alleviates the development of glioma through negatively regulating KLF15
1Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University, Beijing, China. lei0470@ccmu.edu.cn.
Objective:
The purpose of this study was to uncover the role of microRNA-376a-3p (miR-376a-3p) in mediating migratory and invasive capacities of glioma, as well as the underlying mechanism.
Patients And Methods:
MiR-376a-3p levels in 39 collected glioma tissues were detected. After collecting clinical data of included glioma patients, the relationship between miR-376a-3p level and clinical features of glioma was analyzed. Next, regulatory effects of miR-376a-3p on proliferative and metastatic capacities of U251 and T98-G cells were assessed. Downstream genes of miR-376a-3p were searched by bioinformatics approach. At last, the involvement of KLF15 in the development of glioma regulated by miR-376a-3p was explored.
Results:
It was found that miR-376a-3p was lowly expressed in glioma tissues. Low level of miR-376a-3p was linked to high metastasis rate and poor prognosis in glioma. Besides, overexpression of miR-376a-3p suppressed proliferative and metastatic capacities of glioma cells. KLF15, the downstream gene binding miR-376a-3p, was highly expressed in glioma, and displayed a negative correlation to miR-376a-3p. Notably, KLF15 was able to abolish the regulatory effects of miR-376a-3p on phenotypes of glioma cells.
Conclusions:
MiR-376a-3p is related to lymphatic metastasis and distant metastasis of glioma, and alleviates metastasis of glioma by negatively regulating KLF15.
Insights
MicroRNA-376a-3p (miR-376a-3p) is downregulated in glioma, correlating with metastasis and poor prognosis. Upregulating miR-376a-3p inhibits glioma cell proliferation and metastasis by targeting KLF15.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma is a primary brain tumor with significant mortality.
- MicroRNAs play crucial roles in cancer development and progression.
- Understanding the specific roles of microRNAs in glioma is vital for therapeutic development.
Purpose of the Study:
- To investigate the role of microRNA-376a-3p (miR-376a-3p) in glioma cell migration and invasion.
- To elucidate the underlying molecular mechanisms of miR-376a-3p in glioma.
- To explore the relationship between miR-376a-3p expression and clinical features of glioma patients.
Main Methods:
- Quantification of miR-376a-3p levels in glioma tissues.
- Correlation analysis between miR-376a-3p expression and clinical data.
- In vitro assessment of miR-376a-3p effects on glioma cell proliferation and metastasis.
- Bioinformatic identification of miR-376a-3p downstream targets.
- Investigation of KLF15 involvement in miR-376a-3p-mediated glioma regulation.
Main Results:
- miR-376a-3p was found to be downregulated in glioma tissues.
- Lower miR-376a-3p expression correlated with higher rates of metastasis and poorer prognosis.
- Overexpression of miR-376a-3p significantly suppressed glioma cell proliferation and metastatic potential.
- KLF15 was identified as a direct target of miR-376a-3p and was upregulated in glioma.
- KLF15 overexpression counteracted the inhibitory effects of miR-376a-3p on glioma cell phenotypes.
Conclusions:
- miR-376a-3p is implicated in the lymphatic and distant metastasis of glioma.
- miR-376a-3p functions as a tumor suppressor in glioma by inhibiting metastasis.
- The anti-metastatic effect of miR-376a-3p is mediated through the negative regulation of KLF15.
