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Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma
Xuechao Wu1, Yingyi Wang1, Tianfu Yu1
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
Background:
MIR155 host gene (MIR155HG) is a long noncoding RNA that has been considered as the primary micro (mi)RNA of miR-155. MIR155HG plays an essential role in hematopoiesis, inflammation, and tumorigenesis. Our study investigated the clinical significance, biological function, mechanisms, and small-molecule inhibitors of the MIR155HG/miR-155 axis in glioma.
Methods:
We analyzed the expression of the MIR155HG/miR-155 axis and the correlation with glioma grade and patient survival using 2 different glioma gene expression datasets. Biological significance was elucidated through a series of in vitro and in vivo experiments. Furthermore, we conducted a high-throughput screening for small molecules to identify a potential inhibitor of the MIR155HG/miR-155 axis.
Results:
Increased MIR155HG was associated with glioma grade, mesenchymal transition, and poor prognosis. Functionally, MIR155HG reduction by small interfering RNA inhibited cell proliferation, migration, invasion, and orthotopic glioma growth by repressing the generation of its derivatives miR-155-5p and miR-155-3p. Bioinformatics and luciferase reporter assays revealed that protocadherin 9 and protocadherin 7, which act as tumor suppressors by inhibiting the Wnt/β-catenin pathway, were direct targets of miR-155-5p and miR-155-3p, respectively. Finally, we identified NSC141562 as a potent small-molecule inhibitor of the MIR155HG/miR-155 axis.
Conclusions:
Our results demonstrate that the MIR155HG/miR-155 axis plays a critical role in facilitating glioma progression and serves as a prognostic factor for patient survival in glioblastoma. High-throughput screening indicated that the MIR155HG/miR-155 axis inhibitor NSC141562 may be a useful candidate anti-glioma drug.
Insights
The MIR155 host gene (MIR155HG)/miR-155 axis promotes glioma. Inhibiting this axis with NSC141562 may offer a new anti-glioma therapy, showing promise for glioblastoma patients.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The MIR155 host gene (MIR155HG) is a long noncoding RNA and primary source of microRNA (miR)-155.
- MIR155HG/miR-155 axis is implicated in hematopoiesis, inflammation, and tumorigenesis.
Purpose of the Study:
- Investigate the clinical significance and biological role of the MIR155HG/miR-155 axis in glioma.
- Identify potential small-molecule inhibitors targeting this axis.
Main Methods:
- Analyzed MIR155HG/miR-155 expression in glioma datasets, correlating with grade and survival.
- Performed in vitro and in vivo experiments to elucidate biological functions.
- Conducted high-throughput screening for small-molecule inhibitors.
Main Results:
- Elevated MIR155HG correlates with higher glioma grade, mesenchymal transition, and poorer prognosis.
- MIR155HG reduction inhibited glioma cell proliferation, migration, invasion, and tumor growth.
- Identified NSC141562 as a potent inhibitor of the MIR155HG/miR-155 axis.
Conclusions:
- The MIR155HG/miR-155 axis is crucial for glioma progression and a prognostic marker for glioblastoma.
- NSC141562 shows potential as an anti-glioma therapeutic agent.