Competing endogenous RNA networks in the epithelial to mesenchymal transition in diffuse-type of gastric cancer

Abstract

The diffuse-type of gastric cancer is associated with epithelial to mesenchymal transition. Loss of E-cadherin expression is the hallmark of this process and is largely due to the upregulation of the transcription factors ZEB1/2, Snail, Slug, and Twist1/2. However, miRNA and lncRNAs can also participate through these transcription factors which directly target E-cadherin. The competing endogenous RNA (ceRNA) network hypothesis state that lncRNA can sponge the miRNA pool that targets these transcripts. Based on the lack of said networks in the epithelial to mesenchymal transition, we performed a prediction analysis that resulted in novel ceRNA networks which will expand our knowledge of the molecular basis of the diffuse-type of gastric cancer.

The diffuse-type of gastric cancer (DGC), molecularly associated with epithelial to mesenchymal transition (EMT), is increasing in incidence. Loss of E-cadherin expression is the hallmark of the EMT process and is largely due to the upregulation of the EMT-inducing transcription factors ZEB1/2, Snail, Slug, and Twist1/2. However, ncRNA, such as miRNA and lncRNAs, can also participate in the EMT process through the direct targeting of E-cadherin and other EMT-inducing transcription factors. Additionally, lncRNA can sponge the miRNA pool that targets these transcripts through competing endogenous RNA (ceRNA) networks. In this review, we focus on the role of ncRNA in the direct deregulation of E-cadherin, as well as EMT-inducing transcription factors. Based on the relevance of the ceRNA network hypothesis, and the lack of said networks in EMT, we performed a prediction analysis for all miRNAs and lncRNAs that target E-cadherin, as well as EMT-inducing transcription factors. This analysis resulted in novel predicted ceRNA networks for E-cadherin and EMT-inducing transcription factors (EMT-TFs), as well as the expansion of the molecular basis of the DGC.