Abstract 3102: miRNA-mRNA regulatory networks by integrating miRNA and mRNA expression profiling of esophageal squamous cell carcinoma.
Authors: Wei Qiao , Zhao Kuaile , Yu Weiwei , Qin Guangqi , Zhang Zhuanxu , Du Xiang , Sun Menghong 
Published: August 2014

Background: miRNA expression profiling of esophageal squamous cell carcinoma(ESCC) has identified some miRNAs related to the clinical diversity of the disease and this potentially provides novel diagnostic and prognostic tools for ESCC therapy. In order to further understand the associations between miRNA expression and their target mRNA in ESCC, we performed integrating miRNA and mRNA expression profiling in ESCC. Material & Methods: Eight esophageal squamous carcinoma of Stage T2N1MO matched with their corresponding normal tissues was included in the study. Microdissection was performed to assure that more than 70% tumor components were selected for RNA extraction. Microarray technology (Agilent Human miRNA microarray and Agilent whole Human gene expression microarray) was used for miRNA expression and genome wide mRNA profiling. Integrated analysis of miRNAs and their target mRNAs by multi-step bioinformatics methods. Seven important differentiate expressed miRNAs (miR-21, miR-196b, miR-1, miR-29c, miR-125b, miR-195, let-7c) and 4 predicted target mRNAs(CDK-6, VEGFA, IGF1, and FLNC) were selected for future validation in an extended cohort of 50 ESCC by qRT-PCR. The relationship of the miRNA and genes were calculated by their differentiate expression values, and according to the interactions of MicroRNA and genes in Sanger MicroRNA database to create the MicroRNA-Gene-Network by the bioinformatic tools. Results:Compared to esophageal normal tissues, there were 67 differentiately expressed miRNAs and 2992 mRNAs in ESCC. The differentially expressed miRNAs and mRNAs were confirmed by real-time PCR. These differentiated miRNAs and their target genes were associated with many biological processes such as signal transduction, angiogenesis, cell proliferation, cell-cell signaling, response to drug. In the MicroRNA-Gene-Network, the significant pathways were Pathways in cancer, Cell cycle, TGF-beta signaling pathway, p53 signaling pathway, MAPK signaling pathway, mTOR signaling pathway and Jak-STAT signaling pathway. Conclusions: It is the first large-scale study to identify miRNA-mRNA regulatory networks in ESCC by combining expression profiles and bioinformatics analysis demonstrating that miRNA expression is highly associated with the proliferation, prognosis and metastasis of ESCC. Our findings provided a valuable source for future studying the differentially expressed miRNAs and their promising target genes, pathways and processes that may be useful for diagnostic or therapeutic applications in ESCC.

Citation Format: Qiao Wei, Kuaile Zhao, Weiwei Yu, Guangqi Qin, Zhuanxu Zhang, Xiang Du, Menghong Sun. miRNA-mRNA regulatory networks by integrating miRNA and mRNA expression profiling of esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3102. doi:10.1158/1538-7445.AM2013-3102