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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-378a-3p regulates glioma cell chemosensitivity to cisplatin through IGF1R
1Department of Neurosurgery, Yancheng Third People's Hospital, Yancheng City, Jiangsu Province, 224001, China.
Abstract:
Glioma is a type of common intracranial tumor. In this study, we investigated the molecular mechanism by which miR-378a-3p regulates cisplatin (CDDP) chemosensitivity in glioma cells via insulin-like growth factor 1 receptor (IGF1R). U251/CDDP cells were treated with CDDP and transfected with miR-378a-3p mimics, NC mimics, or pcDNA-IGF1R. qRT-PCR was used to measure the differential level of miR-378a-3p. CCK-8 assay was used to test cell proliferation, and flow cytometry was used to analyze apoptosis. The targeting relationship between miR-378a-3p and IGF1R was tested through a dual-luciferase reporter gene assay. In contrast to normal glial cells, the miR-378a-3p level decreased in human glioma U251 cells and had lower expression in U251/CDDP cells. Compared with the CDDP group, miR-378a-3p significantly caused the inhibition of U251/CDDP cell proliferation and enhanced apoptosis in the miR-378a-3p mimics + CDDP group. Another experiment confirmed that IGF1R was a target gene of miR-378a-3p, and overexpression of miR-378a-3p inhibited IGF1R expression. In addition, co-overexpression of miR-378a-3p and IGF1R induced the upregulation of the U251/CDDP cell proliferation and the inhibition of apoptosis in the miR-378a-3p mimics + pcDNA-IGF1R + CDDP group. This study confirmed that miR-378a-3p promoted the sensitivity of glioma cells to CDDP in glioma patients via targeting IGF1R to increase the therapeutic effect during chemotherapy.
Insights
MicroRNA miR-378a-3p enhances chemotherapy sensitivity in glioma by targeting the insulin-like growth factor 1 receptor (IGF1R). This finding offers a new therapeutic strategy for glioma patients undergoing cisplatin treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma is a prevalent intracranial tumor with limited treatment options.
- Chemotherapy resistance remains a significant challenge in glioma treatment.
- MicroRNAs play crucial roles in regulating gene expression and cellular processes.
Purpose of the Study:
- To investigate the role of miR-378a-3p in regulating cisplatin (CDDP) chemosensitivity in glioma cells.
- To elucidate the molecular mechanism involving insulin-like growth factor 1 receptor (IGF1R).
- To explore the potential of miR-378a-3p as a therapeutic target for improving glioma chemotherapy.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure miR-378a-3p levels.
- Cell Counting Kit-8 (CCK-8) assay for cell proliferation assessment.
- Flow cytometry to analyze apoptosis.
- Dual-luciferase reporter gene assay to confirm the targeting relationship between miR-378a-3p and IGF1R.
Main Results:
- miR-378a-3p expression was decreased in human glioma U251 cells and U251/CDDP cells compared to normal glial cells.
- Overexpression of miR-378a-3p inhibited U251/CDDP cell proliferation and enhanced apoptosis.
- IGF1R was identified as a direct target gene of miR-378a-3p, with its expression being inhibited by miR-378a-3p overexpression.
- Co-overexpression of miR-378a-3p and IGF1R reversed the effects on cell proliferation and apoptosis.
Conclusions:
- miR-378a-3p acts as a tumor suppressor in glioma by targeting IGF1R.
- miR-378a-3p significantly enhances the chemosensitivity of glioma cells to cisplatin.
- Targeting miR-378a-3p could be a promising strategy to improve therapeutic outcomes in glioma patients undergoing chemotherapy.
