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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-1908 functions as a glioblastoma oncogene by suppressing PTEN tumor suppressor pathway
Xuewei Xia1, Yong Li2, Wenbo Wang1
1Department of Neurosurgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.
Background:
We aimed to investigate whether miRNA-1908 is an oncogene in human glioblastoma and find the possible mechanism of miR-1908.
Methods:
We investigated the growth potentials of miRNA-1908-overexpressing SW-1783 cells in vitro and in vivo. In order to identify the target molecule of miRNA-1908, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human glioblastoma tissues. We also investigated the miRNA-1908 expression in 34 patients according to the postoperative risk of recurrence.
Results:
The overexpression of miRNA-1908 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MiRNA-1908 significantly suppressed the luciferase activity of mRNA combined with the PTEN 3'-UTR. Furthermore, the expression levels of miRNA-1908 were significantly increased in the patients with a high risk of recurrence compared to that observed in the low-risk patients, and this higher expression correlated with a poor survival.
Conclusions:
miRNA-1908 functions as an oncogene in glioblastoma by repressing the PTEN pathway. MiR-1908 is a potential new molecular marker for predicting the risk of recurrence and prognosis of glioblastoma.
Insights
MicroRNA-1908 (miRNA-1908) acts as an oncogene in glioblastoma by inhibiting the PTEN pathway. Elevated miRNA-1908 levels predict recurrence risk and poor prognosis in glioblastoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma is an aggressive brain tumor with limited treatment options.
- The role of microRNAs (miRNAs) in glioblastoma pathogenesis is an area of active research.
- Investigating novel molecular players like miRNA-1908 is crucial for understanding glioblastoma.
Purpose of the Study:
- To determine if miRNA-1908 functions as an oncogene in human glioblastoma.
- To elucidate the molecular mechanism underlying miRNA-1908's role in glioblastoma.
- To assess miRNA-1908 as a potential biomarker for glioblastoma recurrence and prognosis.
Main Methods:
- Assessed the effects of miRNA-1908 overexpression on glioblastoma cell growth in vitro and in vivo.
- Utilized luciferase reporter assays to identify miRNA-1908's direct molecular targets.
- Examined downstream signaling pathways via immunohistochemistry in patient tissues.
- Correlated miRNA-1908 expression levels with recurrence risk in 34 glioblastoma patients.
Main Results:
- Overexpression of miRNA-1908 significantly enhanced anchorage-independent growth and tumor formation in vivo.
- MiRNA-1908 was found to directly suppress the PTEN pathway by targeting its 3'-UTR.
- Higher miRNA-1908 expression levels were observed in glioblastoma patients with a high risk of recurrence.
- Increased miRNA-1908 expression correlated significantly with poorer patient survival.
Conclusions:
- MiRNA-1908 promotes glioblastoma progression by repressing the PTEN signaling pathway, thus acting as an oncogene.
- MiRNA-1908 represents a promising novel molecular marker for predicting glioblastoma recurrence risk and overall prognosis.
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