Validation of miRNAs as diagnostic and prognostic biomarkers, and possible therapeutic targets in medullary thyroid cancers

验证 miRNA 作为甲状腺髓样癌的诊断和预后生物标志物以及可能的治疗靶点

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作者:Alberto Mondin, Loris Bertazza, Susi Barollo, Maria Chiara Pedron, Jacopo Manso, Ilaria Piva, Daniela Basso, Isabella Merante Boschin, Maurizio Iacobone, Raffaele Pezzani, Caterina Mian, Simona Censi

Conclusion

Silencing miR-21, although not showing synergistic activity with TKIs (tyrosine kinase inhibitors), represents a potential alternative worth exploring as a therapeutic target for MTC.

Methods

We used a specific process to silence miR-21 in two human MTC cell lines. We studied the effect of this anti-miRNA process alone and in combination with cabozantinib and vandetanib, two drugs used in targeted therapy for MTC. We analyzed the effect of miR-21 silencing on cell viability, PDCD4 and CT expression, phosphorylation pathways, cell migration, cell cycle, and apoptosis.

Results

Silencing miR-21 alone resulted in a reduction of cell viability and an increase in PDCD4 levels at both mRNA and protein levels. It also led to a reduction in CT expression at both mRNA and secretion levels. When combined with cabozantinib and vandetanib, miR-21 silencing did not affect cell cycle or migration but was able to enhance apoptosis.

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