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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
MicroRNA-128 increases glioma cell radio-sensitivity by suppressing senescent evasion through oncogene Bmi-1
Junhua Sun1, Lan Ye1, Cuihong Wang1
1Cancer Center, The Second Hospital of Shandong University Jinan, Shandong, P. R. China.
Abstract:
Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Classical treatment of glioblastoma includes surgical resection followed by radiation and chemotherapy. However, radio-resistance is always a challenge for the treatment. MicroRNA-128 was found at lower expression in glioma tissues compared to normal tissue. Its downstream target gene, Bmi-1, was associated with self-renewal and differentiation of neural stem cells and could promote the growth of glioma. Our previous studies showed that expression of Bmi-1 can increase following exposure to X-ray radiation, implying that Bmi-1 may confer radio-resistance to glioma. However, the mechanism is still unclear. In this study, we found that overexpression microRNA 128 could inhibit growth of glioma cells and expression of Bmi-1 (P<0.05). Following exposure the 8 Gy X-ray, the growth of cells was inhibited in the microRNA-128 overexpression group compared to the control group (P<0.05). Expression of Bmi-1 was also lower (P<0.05) and the ratio of senescent cells was higher (P<0.05) in the microRNA-128 overexpression group than the control group. Thus, our results suggest that overexpression of micro-RNA128 could increase the radio-sensitivity of glioma cells through Bmi-1. This mechanism may inhibit senescent evasion in glioma cells and provides a novel view for how to resolve the radio-resistance of glioma and investigate a new strategy for glioma radiation treatment regimens.
Insights
Overexpressing microRNA-128 in glioblastoma (GBM) cells inhibits growth and Bmi-1 expression. This enhances radio-sensitivity, offering a new strategy against radio-resistant brain tumors.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Radiation Oncology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with challenging radio-resistance.
- MicroRNA-128 (miR-128) is downregulated in gliomas, while its target Bmi-1 promotes glioma growth and radio-resistance.
- The mechanism by which Bmi-1 confers radio-resistance remains unclear.
Purpose of the Study:
- To investigate the role of microRNA-128 in glioblastoma radio-resistance.
- To elucidate the mechanism involving Bmi-1 and cellular senescence.
Main Methods:
- Overexpression of microRNA-128 in glioma cells.
- Exposure to 8 Gy X-ray radiation.
- Assessment of cell growth, Bmi-1 expression, and senescence.
Main Results:
- MicroRNA-128 overexpression inhibited glioma cell growth and Bmi-1 expression.
- Radiation exposure showed reduced cell growth in miR-128 overexpressing cells.
- Lower Bmi-1 expression and increased senescence were observed in the miR-128 overexpression group.
Conclusions:
- Overexpression of microRNA-128 enhances glioma cell radio-sensitivity by downregulating Bmi-1.
- This mechanism may involve inhibiting senescent evasion, providing a novel strategy for glioma radiation therapy.
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