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RNF213 suppresses carcinogenesis in glioblastoma by affecting MAPK/JNK signaling pathway
1Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Purpose:
Glioblastoma is the most common malignant brain tumor in central nervous system. Due to absence of the mechanism underlying glioblastoma, the clinical outcome is poor. RNF213 is a ring finger protein and mutation in RNF213 gene is detected in cancers. But the role of RNF213 in glioblastoma is unknown.
Methods:
RNF213 expression was detected by qPCR, western blotting, IHC technology. RNF213 was overexpressed in plasmid pcDNA3.1. Assays including CCK-8, plate colony formation, wound healing, transwell and FITC/PI dye were used to detect cell behaviors.
Results:
RNF213 was shown to express much lower in tumor tissues and in tumor cell lines compared to control. The patients with higher RNF213 expression displayed longer survival time. When RNF213 was overexpressed in U87MG cells, cell proliferation and colony formation were inhibited significantly. The ability of cell migration and invasion was also suppressed. FAC analysis demonstrated that cell apoptosis was increased after RNF213 overexpression. But cell cycle distribution was not affected by RNF213. Then the expression level of MEKK1, JNK, c-Jun, and cdc42 was decreased after RNF213 overexpression, but increased reversely when RNF213 was knocked down by RNAi technology.
Conclusions:
RNF213 suppresses carcinogenesis and affects MAPK/JNK signaling pathway in glioblastoma. This study suggests that RNF213 might be a promising target for therapy of glioblastoma.
Insights
RNF213 protein expression is low in glioblastoma, and higher levels correlate with longer survival. Overexpressing RNF213 inhibits glioblastoma cell growth, migration, and invasion, suggesting it as a potential therapeutic target.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioblastoma is a prevalent and aggressive central nervous system malignancy with poor prognosis due to poorly understood mechanisms.
- RNF213, a ring finger protein, has known mutations in various cancers, but its role in glioblastoma remains unelucidated.
Purpose of the Study:
- To investigate the role of RNF213 in glioblastoma.
- To determine the potential of RNF213 as a therapeutic target for glioblastoma.
Main Methods:
- RNF213 expression was quantified using qPCR, western blotting, and immunohistochemistry.
- Cell proliferation, colony formation, migration, invasion, and apoptosis were assessed after RNF213 overexpression or knockdown.
- The study utilized cell lines and tumor tissues for analysis.
Main Results:
- RNF213 expression was significantly lower in glioblastoma tissues and cell lines compared to normal controls.
- Higher RNF213 expression in patients correlated with improved survival outcomes.
- Overexpression of RNF213 suppressed glioblastoma cell proliferation, colony formation, migration, and invasion, while increasing apoptosis.
- RNF213 modulated the expression of key signaling molecules including MEKK1, JNK, c-Jun, and cdc42.
Conclusions:
- RNF213 acts as a tumor suppressor in glioblastoma, inhibiting carcinogenesis.
- RNF213 influences glioblastoma progression through the MAPK/JNK signaling pathway.
- RNF213 presents a promising therapeutic target for glioblastoma treatment.
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