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Identification and characterization of human MIBP1 gene in glioma cell differentiation
Lijun Sun1, Xiwen Chen, Xingnan Jin
1Department of Neurosurgery, Tianjin Huanhu Hospital, 122 Qixiangtai Road, Tianjin, 300060, People's Republic of China, sunlijun0808@sina.com.
Abstract:
Malignant gliomas are the most common and lethal intracranial tumors; differentiation therapy is a promising candidate for their treatment. In order to reveal the mechanisms related to glioma differentiation, after confirming that differentiation was induced by sodium phenylbutyrate in SHG-44 human glioma cells, RNA arbitrary primer differential display was used to screen differentially expressed genes. One gene was found to be upregulated by differential display, and this was also confirmed by reverse northern blot and quantitative real-time PCR analysis. After it was cloned and sequenced, the 505-bp fragment was identified as the MIBP1 (c-myc intron-binding protein 1) gene, also named Hivep2/MBP-2/Schnurri-2. Quantitative real-time PCR analysis of 30 human tissue samples revealed that the expression of MIBP1 tended to decrease with increasing WHO grade and was significantly depressed in the high malignancy gliomas group (WHO grade IV). We cloned and sequenced the MIBP1 gene, which was accepted by GenBank as number DQ231041. Finally, transfection of MIBP1 in a reverse transcription vector into glioma cells inhibited cell growth, induced differentiation, and blocked the cell cycle. Here, we identify and describe the structure and function of a differentiation-related gene, human MIBP1, in human glioma.
Insights
Malignant gliomas are lethal brain tumors. Researchers identified MIBP1 (c-myc intron-binding protein 1) as a gene that inhibits glioma cell growth and promotes differentiation, offering a new therapeutic target.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Genetics
Background:
- Malignant gliomas represent the most frequent and fatal primary brain tumors.
- Differentiation therapy shows promise for treating gliomas by inducing tumor cell maturation.
- Understanding the molecular mechanisms of glioma differentiation is crucial for developing effective treatments.
Purpose of the Study:
- To identify genes involved in glioma cell differentiation induced by sodium phenylbutyrate.
- To characterize the function of the identified differentiation-related gene, MIBP1, in human glioma.
Main Methods:
- Sodium phenylbutyrate treatment of SHG-44 human glioma cells.
- RNA arbitrary primer differential display for gene screening.
- Reverse northern blot and quantitative real-time PCR for gene validation.
- Gene cloning, sequencing, and GenBank submission (DQ231041).
- MIBP1 transfection and cell cycle analysis.
Main Results:
- MIBP1 (c-myc intron-binding protein 1) was identified as upregulated during glioma cell differentiation.
- MIBP1 expression decreased with increasing WHO grade and was significantly lower in high-grade gliomas.
- Transfection of MIBP1 inhibited glioma cell growth, induced differentiation, and blocked cell cycle progression.
Conclusions:
- MIBP1 is a differentiation-related gene in human glioma.
- Downregulation of MIBP1 correlates with glioma malignancy.
- MIBP1 functions as a tumor suppressor by inhibiting cell growth and promoting differentiation, representing a potential therapeutic target.
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