MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma

Figure 1 MicroRNAs targeting receptor tyrosine kinase signaling pathway in esophageal squamous cell carcinoma metastasis. The receptor tyrosine kinases (RTKs) signaling pathway effect many signals, including epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF) and their receptors, as well as intracellular signaling pathways, such as mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K). The dysregulation of miRNAs on the RTK signaling pathway is play important roles in ESCC metastasis[10,12,13,15,23,24,26,30-33,36,39,44,50,53,62,63,66,69,70-73,76-78,80,81,83,85,86,88-91,93,95,97,100-104,107-109,112,117,123,125,128,140-144,146,151,154,160,163,169,174,175,178-180,185-187,189,192,193,195,199,200,203-205,207,208,216,222,224,226,227,229,231,232,234,235,244,253,257,260-265,266,269-271,273,274,278,279,281,282,285,289-309,311]. ZEB1/2, Snail1/2, E-cadherin, N-cadherin, C-myc, Vimentin and MMPs are specific target and key factors for esophageal squamous cell carcinoma metastasis. “Green” and “Red” indicated oncomiRs and tumor-suppressive miRNAs, respectively. The dashed arrow and solid arrow indicated direct targeting effect and indirect targeting effect, respectively.

Figure 2 MicroRNAs targeting the pathways of Wnt/β-catenin, IL6/Stat3, and TGF-β in esophageal squamous cell carcinoma metastasis. In esophageal squamous cell carcinoma (ESCC), miRNAs serve as crucial effector to Wnt/β-catenin, IL-6/STAT3 and TGF-β signalings, which is consistently involved in cancer metastasis[9,12,14,23,27,28,33,44,59,61,70,73,78,80,81,83,85,86,88-91,93-95,109,111,113,114,116,118,119,142-144,151,156,161,164,165,169,174,178,181,189,193,195,200,201,204,209,211,215,219,227,229,235,238,253,263,270,273,284-287,289,310]. Wnt/β-catenin signaling includs Wnts, receptors (such as Frizzled, FZD and low-density lipoprotein receptor-related proteins, LRP), Dishevelled (Dsh/Dvl), β-catenin, glycogen synthase kinase 3β (GSK-3β), Axin, APC (adenomatous polyposis coli), IL-6 is known to activate the downstream JAK/STAT3 signaling, and canonical TGF-β pathway is mediated by SMAD2, SMAD3, and SMAD4. ZEB1/2, Snail1/2, E-cadherin, N-cadherin, C-myc, Vimentin and MMPs are specific target and key factors for ESCC metastasis. “Green” and “Red” indicated oncomiRs and tumor-suppressive miRNAs, respectively. The dashed arrow and solid arrow indicated direct targeting effect and indirect targeting effect, respectively.