Mps1 Knockdown in Glioblastoma Induces DNA Damage and up Regulation of Histone Methyltransferase SETD2
Objectives: The diagnosis and treatment of glioblastoma are challenging due to the fast-growing nature of the tumour. Identifying new hallmarks of the disease is important for improving patient care. This study investigates the association between the overexpression of cell cycle checkpoint kinase Mps1 and patient outcomes in glioblastoma.
Methods: We analyzed available online transcriptomic and proteomic data following Mps1 knockdown in U251 glioblastoma cells. Gene ontology enrichment analysis was performed to identify key pathways activated after Mps1 knockdown.
Results: The analysis revealed that cell cycle transition and the intrinsic apoptosis pathway in response to DNA damage were the top pathways activated following Mps1 knockdown. Three genes and proteins emerged as common targets: BCL2L1 (encoding the protein Bcl-xL) was downregulated, while CDKN1A (encoding p21) and SETD2 (encoding the histone methyltransferase SETD2) were upregulated.
Conclusion: This study is the first to report the association of Mps1 inhibition with SETD2 overexpression, providing a new perspective for glioblastoma therapeutics.
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