RESUMO
Aberrant Siglec expression in the tumour microenvironment has been implicated in tumour malignancies and can impact tumour behaviour and patient survival. Further to this, engagement with sialoglycans induces masked antigen recognition and promotes immune evasion, highlighting deregulated immune function. This necessitates the elucidation of their expression profiles in tumour progression. MicroRNAs (miRNAs) mediated targeting represents a novel approach to further elucidate Siglec potential and clinical relevance. Although miRNA activity in Siglec expression remains limited, we highlight current literature detailing miRNA:Siglec interactions within the tumour landscape and provide insights for possible diagnostic and therapeutic strategies in targeting the Siglec/sialic acid axis.
Assuntos
Progressão da Doença , MicroRNAs , Neoplasias , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Animais , Microambiente Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3' untranslated region (3'UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management.