Abstract #552: Identification of differentially expressed microRNAs based on esophageal cancer signatures

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive and lethal malignancies in the world. Patients with ESCC are very poor prognosis because most cases are not diagnosed until the disease is at advanced stage. The understanding of the new molecular pathways of ESCC carcinogenesis would be helpful in improving diagnosis and therapy of the disease. MicroRNA(miRNA) are endogenous short non-coding RNA molecules, which regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Growing evidence has suggested that miRNAs are aberrantly expressed in many human cancers and they may play significant roles in carcinogenesis and progression of cancer. MiRNA over-expression could result in down-regulation of tumor suppressor genes, whereas their under-expression could lead to oncogenes activation. A few studies of the relationship between miRNAs and ESCC have been reported, but the functions of each miRNAs in ESCC are still unknown absolutely. In the present study, we examined differentially expressed miRNAs in ESCC specimens and identified differentially expressed miRNAs from head and neck squamous cell cancer expression signatures. These specimens were obtained from patients in the Chiba University hospital, Japan from 2003 to 2007 with informed consent and agreement. In all the samples, clinicopathological information (age, gender, pathology, differentiation, TNM classification, tumor stage, and survival time after surgery) was available. In this study, we identified 14 up-regulated mature miRNAs and 15 down-regulated mature miRNAs. Transient transfection of down-regulated miRNAs (such as miR-504, miR-145, miR-1, miR-375, and miR-326) inhibited cell growth in cancer cell line. These miRNAs might play tumor suppressor role in the proliferative process of the ESCC. To search target genes of miR-504, combining experimental and bioinformatics data identified several cancer-related genes. Our miRNA expression signatures and identification of target genes may provide an understanding of the potential mechanisms in ESCC carcinogenesis. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 552.