Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V11
Höfundar / Authors: Hafþór Daði Halldórsson, Linda Viðarsdóttir, Stefán Þórarinn Sigurðsson
Starfsvettvangur / Affiliations: Háskóli Íslands
Kynnir / Presenter: Hafþór Daði Halldórsson
Osteosarcoma mainly affects children and young adults where 5-year survival for patients remains at about 67% without therapeutic advances in the past 30 years. FGD5-AS1, a lncRNA, has been found to be upregulated in osteosarcoma tissue and is associated with poor prognosis. FGD5-AS1 is involved in various oncogenic processes including proliferation, metastasis and drug resistance. Our preliminary data suggest a role in autophagy, mitochondrial metabolism and drug resistance. A genome-wide co-expression analysis indicated that FGD5-AS1 expression correlated with several genes related to endosomal fusion and autophagy. Knockdown of FGD5-AS1 negatively affects these pathways, as demonstrated by confocal imaging, showing reduced expression of the protein LC3B and disruption of binding to the endosomal FYVE domain. Reduced LC3B signal was confirmed by western blot upon FGD5-AS1 knockdown. Furthermore, by using RNA immunoprecipitation (RIP) we confirmed an interaction between FGD5-AS1 and LC3B. FGD5-AS1 knockdown cells are smaller in size and show reduced mitochondrial activity in Seahorse mito stress assays. Along with dysregulation in autophagy and respiration, real-time Incucyte measurements indicate that knockdown of FGD5-AS1 increases survival when given doxorubicin and etoposide, suggesting drug resistance. FGD5-AS1 regulates autophagy and mitochondrial metabolism in osteosarcoma. Its knockdown promotes drug resistance, making it a target to overcome chemoresistance.