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

• Activation of S100P/RAGE signaling induces expression of the oncomiR-miR-21.
• The induction of miR-21 by S100P/RAGE signaling is AP-1 dependent.
• S100P, RAGE receptor, and miR-21 expression are inversely correlated with the miR-21 target gene RECK in human colorectal cancers.

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.