An article published this year in “Human
Molecular Genetics” using our “FITC AnnexinV” and our “PI/RNAsesolution” by our customers from the University of Coimbra, Portugal, in the
analysis of how High-throughput screening uncovers miRNAs enhancing
glioblastoma cell susceptibility to tyrosine kinase inhibitors. Congrats and Thanks.
Summay:
Glioblastoma (GBM) is a deadly and
therapy resistant malignant brain tumour, characterized by an aggressive and
diffuse growth pattern, which prevents complete surgical resection. Despite
advances in the identification of genomic and molecular alterations that fuel
the tumour, average patient survival post-diagnosis remains very low (∼14.6-months). In addition to being highly heterogeneous, GBM tumour
cells exhibit high adaptive capacity to targeted molecular therapies owing to
an established network of signalling cascades with functional redundancy, which
provides them with robust compensatory survival mechanisms. Here, we
investigated whether a multimodal strategy combining multitargeted tyrosine
kinase inhibitors (MTKIs) and microRNA (miRNA) modulation could overcome the
signalling pathway redundancy in GBM and, hence, promote tumour cell death. By
performing a high-throughput screening, we identified a myriad of miRNAs,
including those belonging to the miR-302-3p/372-3p/373-3p/520-3p family, which
coordinately act with the MTKI sunitinib to decrease GBM cell viability. Two
members of this family, hsa-miRNA-302a-3p and hsa-miRNA-520 b, were found to
modulate the expression of receptor tyrosine kinase mediators (including AKT1,
PIK3CA and SOS1) in U87 and DBTRG human GBM cells. Importantly, administration
of mimics of these miRNAs with sunitinib or axitinib resulted in decreased
tumour cell proliferation and enhanced cell death, whereas no significant
effect was observed when coupling miRNA modulation with temozolomide, the
first-line drug for GBM therapy. Overall, our results provide evidence that
combining the ‘horizontal’ inhibition of signalling pathways promoted by MTKIs
with the ‘vertical’ inhibition of the downstream signalling cascade promoted by
hsa-miR-302a-3p and hsa-miR-520 b constitutes a promising approach towards GBM
treatment.
Reference:
Product links:
FITC AnnexinV
PI/RNAse Solution
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