Abstract 179: Regulation of stromal miR-125b on normal colonic epithelial cell renewal and its putative role in tumorigenesis

MicroRNAs (miRNAs) are small non-coding RNAs which exert their effects by post-transcriptionally silencing target mRNAs. Deregulation of miRNA expression is a frequent event in tumorigenesis. MiR-125b is a highly conserved miRNA among various species and is composed of three homologs: hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125-2. The tumorigenic roles of miR-125b have been studied in various cancers including prostate, colon, glioma etc, and studies have demonstrated that it can act as a tumor suppressor or an oncogene depending on the cellular context. It was characterized as an oncogene in prostate cancer and glioma through down-regulation of pro-apoptotic regulators BAK1 and Bcl-2 modifying factor (BMF), respectively. In colon cancer, a recent clinico-pathological study showed that high expression of miR-125b was associated with tumor invasion and poor prognosis. However, the localization of miR125b in normal colon and tumors is currently unknown. Therefore, we aimed to address the precise expression and the functional role of miR-125b in normal colon, which may provide insight on its potential oncogenic effects during carcinogenesis. We performed gene expression analysis of miR-125b in normal colon tissues from 16 pairs of colon top versus basal crypts and 4 pairs of crypts versus stroma by real-time RT-PCR. Colon top and basal crypts were microdissected from frozen sections, whereas pure normal crypts and stromal fractions were isolated from freshly resected human colon specimens. We found that miR-125b was significantly enriched in the basal crypts (p