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

• Published in: FEBS letters Vol. 589; no. 18; pp. 2388 - 2393
• Main Authors: Mercado-Pimentel, Melania E., Onyeagucha, Benjamin C., Li, Qing, Pimentel, Angel C., Jandova, Jana, Nelson, Mark A.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 19-08-2015
• Subjects: AP-1; Calcium-Binding Proteins - metabolism; Cell Line, Tumor; Colon cancer; Colonic Neoplasms - pathology; Databases, Genetic; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins - metabolism; Humans; Inflammation; Metastasis; microRNAs; MicroRNAs - genetics; miR-21; Neoplasm Proteins - metabolism; Promoter Regions, Genetic - genetics; RAGE; Receptor for Advanced Glycation End Products; Receptors, Immunologic - metabolism; RECK; Signal Transduction; TCGA; Transcription Factor AP-1 - metabolism; Transcription, Genetic; Up-Regulation; microRNAs; Colon cancer; Inflammation; Metastasis; miR-21; RAGE; RECK; AP-1; TCGA
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2015.07.010

•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.