Turner et al. [49] proposed that soluble SCF-receptors regulate kit activation.
Interferon gamma (Ifng) down regulates Kit ligand (Kitl) and Epor and may be an important contributor to anaemia of infection [33].
Similarly, it can not be firmly concluded that miR-17 and miR-20a directly regulate KIT.
This result is consistent with the ability of Lyn to down-regulate Kit expression.
We show that Epo down-regulates Kit expression and that Lyn kinase behaves as a mediator of SCF signaling through controlling Kit expression.
Furthermore, enforced expression of Lyn in the cell lines increased cell proliferation in response to Epo, but reduced cell growth in response to SCF in accordance with Lyn ability to down-regulate Kit expression.
Although miR-17 and miR-20a regulate ETV1 and miR-222 regulates KIT, they will most likely also target additional genes in the context of GIST cells.
It is therefore possible that a similar mechanism exists in EAC and SCC cells, so miR-148a down-regulates KIT and, by inhibiting its signaling activity, increases cisplatin efficacy.
Down-regulated KIT expression in thyroid tumors is in contrast with the over-expression of other tyrosine kinase receptors, such as c-RET and c-MET, or oncogenes, such as c-RAS, indicating that the signaling pathways of different tyrosine kinase receptors can control opposite biological mechanisms, or alternatively affect cell proliferation or differentiation in a specific cell type.
We found that c-Kit protein levels were higher in older individuals (Fig. 4B D), but that c-Kit mRNA levels were not changed between the different groups, consistent with the fact that miR-221 has been reported to predominantly regulate c-Kit translation rather than c-Kit mRNA levels [26].
