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RASSF10 regulates bone invasion of growth hormone-secreting adenomas via exosomes
Tianyu Wang1, Haibin Liu1, Zhenhua Ji1
1Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 20003, China.
Background:
Invasion of pituitary growth hormone-secreting adenoma into surrounding tissues poses a challenge for complete resection in surgery, which is the main reason for recurrence of this type of cancer. Studies have shown that abnormal methylation of RASSF10 can promote the expression of MDM2 and regulate the tumor microenvironment by affecting the secretion of exosomes. In the present study, we aim to uncover the specific underlying mechanism of this effect.
Method:
Transwell co-culture assays was performed using GT1.1 cells or exosomes and RAW264.7 cells. RAW264.7 cells were collected for invasion, proliferation and apoptosis assays, RT-qPCR and western blotting. RNA-seq was performed and used to assess the potential molecular pathways of the effect of GT1.1 cell-exosomes on RAW264.7 cells.
Results:
GT1.1 cells with reduced RASSF10 expression could promote the proliferation and migration of RAW264.7 cells, and promote their expression of osteoclast markers TRAP and CK. The effect of GT1.1 cell exosomes on the RAW264.7-cell phenotype was shown to be achieved through the RASSF10-MDM2 pathway. RNA-seq allowed the identification of PI3K-AKT, MAPK, and calcium signaling as important in this regulation system of RASSF10-MDM2.
Conclusion:
Our results indicate that GT1.1 cells activate PI3K-AKT, MAPK and calcium signaling via the RASSF10-MDM2 pathway, and promote the differentiation of RAW264.7 cells into osteoclasts through exosomes. This study may provide new ideas to aid in early diagnosis, prognostic assessment and treatment of aggressive pituitary adenomas.
Insights
Reduced RASSF10 expression in pituitary adenoma cells promotes osteoclast differentiation via exosomes, activating key signaling pathways. This discovery offers new avenues for diagnosing and treating aggressive pituitary tumors.
Area of Science:
- Endocrinology and Oncology
- Molecular Biology
- Cell Biology
Background:
- Pituitary growth hormone-secreting adenoma invasion complicates surgical resection, leading to cancer recurrence.
- Aberrant RASSF10 methylation influences tumor microenvironment by affecting exosome secretion and MDM2 expression.
Purpose of the Study:
- To elucidate the specific molecular mechanism by which RASSF10 affects pituitary adenoma progression.
- To investigate the role of exosomes in mediating the interaction between pituitary adenoma cells and the tumor microenvironment.
Main Methods:
- Transwell co-culture assays using pituitary adenoma GT1.1 cells/exosomes and RAW264.7 cells.
- Assessment of RAW264.7 cell invasion, proliferation, apoptosis, gene expression (RT-qPCR), and protein levels (western blotting).
- RNA sequencing (RNA-seq) to identify molecular pathways involved in GT1.1 cell-exosome mediated effects on RAW264.7 cells.
Main Results:
- Reduced RASSF10 expression in GT1.1 cells enhanced RAW264.7 cell proliferation, migration, and osteoclast marker expression (TRAP, CK).
- GT1.1 cell-derived exosomes mediated these effects through the RASSF10-MDM2 pathway.
- RNA-seq identified PI3K-AKT, MAPK, and calcium signaling pathways as crucial in the RASSF10-MDM2 regulatory system.
Conclusions:
- GT1.1 cells, via exosomes and the RASSF10-MDM2 pathway, activate PI3K-AKT, MAPK, and calcium signaling to promote RAW264.7 cell differentiation into osteoclasts.
- Findings suggest potential for novel diagnostic, prognostic, and therapeutic strategies for aggressive pituitary adenomas.
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