P3.10 Microrna Profiling in Gastric Cancer

Abstract

ABSTRACT Background and Aims Gastric cancer is the fourth most common malignancy and the second leading cause of cancer death in both sexes worldwide. Despite a global decrease in incidence, gastric cancer remains a disease of prominent morbidity and mortality, especially in Eastern Asia. The clinical outcome of gastric cancer has gradually improved, but the survival rate of patients with advanced gastric cancer is still disappointing. Achieving a better understanding of molecular aberrations associated with gastric carcinogenesis might identify new diagnostic and therapeutic strategies for this disease.MicroRNAs (miRNAs) recently emerged as prominent regulators of cancer processes. MicroRNAs are small, 18- to 24-nucleotide noncoding RNAs, with profound impact on many processes that are frequently disrupted during malignant transformation, including cell proliferation, apoptosis, stress responses, maintenance of stem cell potency and metabolism. Here we aim to identify miRs whose deregulated expression leads to the activation of oncogenic pathways in human gastric cancers. Methods 39 out of 123 tumoral and matched peritumoral gastric specimens from three independent Europian subsets of patients were analyzed for the expression of 851 human miRs using Agilent Platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by qPCR. In vitro and in vivo experimental assays were employed to test the tumor suppressor activities of miR-204 and to functionally validate its mRNAs targets. Results miR-204 falls into a cluster of 8 miRs differentially expressed between tumoral and peritumoral samples in all three analyzed subsets. Its downregulation has prognostic value and correlates with T status. Ectopic expression of miR-204 inhibited colony forming ability, migration and tumor engraftment of gastric cancer cells. Conclusions microRNAs are differentially expressed in gastric tumors and underline specific genetic alterations. MiR 204 is significantly down-regulated in gastric tumor specimens compared to matched peritumoral tissues. These findings strongly indicate that down-regulation of miR-204 in gastric tumors might coincide with loss of tumor suppressor activity and consequently favor gastric transformation.