The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells

S100P/RAGE信号通路调控结肠癌细胞中microRNA-21的表达

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作者:Melania E Mercado-Pimentel, Benjamin C Onyeagucha, Qing Li, Angel C Pimentel, Jana Jandova, Mark A Nelson

Abstract

S100P signaling through the receptor for advanced glycation end-products (RAGE) contributes to colon cancer invasion and metastasis, but the mechanistic features of this process are obscure. Here, we investigate whether activation of S100P/RAGE signaling regulates oncogenic microRNA-21 (miR-21). We show that exogenous S100P up-regulates miR-21 levels in human colon cancer cells, whereas knockdown of S100P results in a decrease of miR-21. Furthermore, blockage of RAGE with anti-RAGE antibody suppresses S100P induction of miR-21. In addition, we found that S100P induction of miR-21 expression involves ERK and is suppressed by the MEK inhibitor U0126. Also, S100P treatment stimulates the enrichment of c-Fos, and AP-1 family members, at the miR-21 gene promoter.

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