Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/233977
Title: INVESTIGATION OF THE ROLE OF METTL8 IN GLIOBLASTOMA
Authors: LEE WOON LI BERNICE
ORCID iD:   orcid.org/0000-0003-4081-9435
Keywords: METTL8, glioblastoma, stem cells, mitochondria
Issue Date: 17-Jun-2022
Citation: LEE WOON LI BERNICE (2022-06-17). INVESTIGATION OF THE ROLE OF METTL8 IN GLIOBLASTOMA. ScholarBank@NUS Repository.
Abstract: Glioblastoma (GBM) is driven by stem-like cancer cells known as GBM stem cells (GSCs). Clinically, the failure of conventional anti-cancer therapies has been widely attributed to GSCs. Hence, studies are needed for novel therapeutic strategies to target this subpopulation. Literature has demonstrated a metabolic dependency of GSCs on the mitochondria and oxidative phosphorylation to fuel GBM. Very recently, methyltransferase-like 8 (METTL8) has been shown to catalyze the formation of m3C32 in the anticodon loop of tRNASer(UCN) and tRNAThr. We demonstrate that mitochondrial translation is augmented in GBM which correlates with H2AZ-mediated, high METTL8 expression. Loss-of-function analyses further revealed a role of METTL8 in regulating GSC proliferation/self-renewal, invasiveness, stemness and tumorigenicity due to the disruption of polysome formation in the mitochondria and hence OXPHOS impairment. Interestingly, transcriptomic analysis of METTL8 depleted versus intact GSC identified the downregulation of genes that are enriched in receptor tyrosine kinase signaling pathways. These gene expression changes are associated with adaptive chromatin remodelling. Our current data supports a novel role of METTL8 in influencing GSC hallmarks via nuclear-mitochondrial crosstalk. As there are no available inhibitors against METTL8, we are also exploring mechanism-guided combinatorial treatments to indirectly target GBM’s dependency on mitochondrial translation.
URI: https://scholarbank.nus.edu.sg/handle/10635/233977
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