AI Article Synopsis

  • RasGRP3 is found to be overexpressed in papillary thyroid cancer (PTC) tissues and cell lines, suggesting it plays a significant role in the disease.
  • Downregulation of RasGRP3 via small interfering RNA reduces cell proliferation and migration, as well as tumor growth, indicating its oncogenic properties.
  • The study reveals that RasGRP3 influences PTC progression through the activation of MDM2 via the Akt signaling pathway, highlighting its potential as a therapeutic target.

Article Abstract

Accumulating evidence has shown that Ras guanylnucleotide releasing peptide 3 (RasGRP3) is up-regulated in several distinct cancer types; however, its role in papillary thyroid cancer (PTC) remains unclear. In this study, we demonstrate that RasGRP3 was overexpressed in PTC tissues and cell lines. Downregulation of RasGRP3 using small interfering (si) RNA significantly inhibited PTC cell proliferation and migration in vitro, and tumor growth in vivo, reflecting an oncogenic role of RasGRP3 in PTC. We subsequently identified that the expression of mouse double minute 2 homolog (MDM2) and phosphorylated Akt (p-Akt) was significantly decreased in RasGRP3-downregulated PTC cells. Overexpression of MDM2 attenuated the function of si-RasGRP3. Taken together, our data show that RasGRP3 exerts its oncogenic effect in PTC through Akt-mediated MDM2 activation. RasGRP3 may serve as a potential new therapeutic target for PTC.

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Source
http://dx.doi.org/10.1016/j.gene.2017.08.024DOI Listing

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