Glioblastoma is one of the most aggressive and deadly forms of brain cancer, with a median survival rate of just 15 months. Despite advances in treatment options, the prognosis for patients with glioblastoma remains poor, highlighting the urgent need for a better understanding of the molecular mechanisms driving this disease.
A recent study published in Cell Discovery sheds light on the role of RBBP6 in sustaining glioblastoma stem cells through CPSF3-dependent alternative polyadenylation. Glioblastoma stem cells are a subpopulation of cancer cells that possess stem cell-like properties, including self-renewal and differentiation capabilities, and are thought to be responsible for tumor initiation, progression, and resistance to therapy.
The study, led by researchers from the Chinese Academy of Sciences, found that RBBP6, a protein involved in RNA processing and gene expression regulation, is highly expressed in glioblastoma stem cells compared to non-stem cancer cells. Through a series of experiments, the researchers demonstrated that RBBP6 plays a critical role in maintaining the stemness of glioblastoma cells by promoting alternative polyadenylation of key genes involved in cell proliferation and survival.
Alternative polyadenylation is a process that regulates gene expression by determining the length of the 3′ untranslated region (UTR) of mRNA transcripts. In glioblastoma stem cells, RBBP6 interacts with CPSF3, a key component of the polyadenylation machinery, to promote the usage of distal polyadenylation sites in target genes. This results in the production of mRNA isoforms with longer 3′ UTRs, which are more stable and resistant to degradation, leading to increased expression of genes that support stem cell properties.
The researchers also found that inhibition of RBBP6 or CPSF3 in glioblastoma stem cells reduced their self-renewal capacity and tumor-forming ability in mouse models, highlighting the potential therapeutic implications of targeting this pathway in glioblastoma treatment.
Overall, this study provides valuable insights into the molecular mechanisms underlying glioblastoma stem cell maintenance and identifies RBBP6 as a potential therapeutic target for this deadly disease. Further research is needed to fully understand the complex interplay between RBBP6, CPSF3, and alternative polyadenylation in glioblastoma, but these findings represent a promising step towards developing more effective treatments for patients with this devastating form of brain cancer.
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- Source Link: https://platohealth.ai/rbbp6-maintains-glioblastoma-stem-cells-through-cpsf3-dependent-alternative-polyadenylation-cell-discovery/