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Updated: May 27, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
FoxM1 and its association with matrix metalloproteinases (MMP) signaling pathway in papillary thyroid carcinoma
Maqbool Ahmed1, Shahab Uddin, Azhar R Hussain
1Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, MBC#98-16, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Context:
Forkhead boxM1 (FoxM1) transcription factor has been shown to promote pathogenesis of several malignancies. FoxM1 has also been shown to be associated with matrix metalloproteinases (MMP) in various cancers. However, little is known about its function in papillary thyroid carcinoma (PTC).
Objective:
In this study, we investigated the role of FoxM1 in pathogenesis in a large series of PTC in a tissue microarray format followed by in vitro and in vivo studies using PTC cell lines and nude mice.
Design:
Expression of FoxM1 and its associated proteins were investigated in Middle Eastern PTC samples by immunohistochemistry. Apoptosis was measured by flow cytometry and immunoblotting. Invasion and migration studies were performed using 8-μm Transwell plates.
Results:
FoxM1 was overexpressed in 28.4% of PTC and significantly associated with activated matrix metalloproteinase-9 (MMP-9) (P = 0.0004), X-linked inhibitor of apoptosis protein (XIAP) (P = 0.0024), and B-cell lymphoma-extra large (Bcl-XL) (P = 0.0014) expression. Treatment of PTC cell lines with thiostrepton, an inhibitor of FoxM1, resulted in inhibition of cell viability via induction of apoptosis. In addition, thiostrepton treatment of PTC cells or expression of FoxM1-specific small interfering RNA down-regulated expression of FoxM1 accompanied with decreased MMP-2 and MMP-9 expression. Furthermore, inhibition of FoxM1 attenuated migration and invasion of PTC cells. Interestingly, overexpression of FoxM1 rescued the effects of thiostrepton in PTC cell lines. Finally, treatment of PTC cell line xenografts with thiostrepton resulted in growth inhibition of tumors in nude mice via down-regulation of FoxM1 and MMP-9 and MMP-2.
Conclusion:
Altogether, this is the first study showing that FoxM1 and its associated signaling pathway play a critical role in the pathogenesis of PTC and may be a potential target for therapeutic intervention for treatment of these cancers.
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