13513 Background: MicroRNAs (miRNAs) are small non-cording RNAs (∼ 22 nucleotide) that regulate gene expression by suppressing their target mRNAs at post-transcriptional level. Previous studies from our group have identified a number of dis-regulated miRNAs due to the loss of p53 tumor suppressor in cancer cell lines. As part of the efforts to further investigate the in vivo biological significance of these miRNAs, the expression of both hsa-let-7g and hsa-miR-200c were investigated using formalin-fixed paraffin embedded (FFPE) colon cancer specimens to evaluate the potential correlation with chemosensitivity and tumorigenesis. Methods: Forty-six patients with recurrent or residual colon cancer lesion assessable were treated with 5-FU based antimetabolite S-1. This includes twenty-one pair of tumor and normal samples. Total RNAs were isolated from these samples FFPE specimens (contains either > 90% normal or > 90% tumor tissue). cDNAs were synthesized using primers specific for hsa-let-7g, hsa-miR-200c and internal control 5S. The expression levels of each particular miRNAs were quantified using real time qRT-PCR analysis. The expression level of each miRNAs was quantified by measuring the difference of threshold cycle (CT) of candidate miRNAs and internal control 5S (Δ-CT). Results: The expression level of hsa-let-7g was significantly higher in tumor tissues compare to normal tissues (p=0.0026; Wilcoxon test). In the forty-six tumor tissues, the expression level of hsa-let-7g in disease response group (patients group of complete response, partial response and no change after chemotherapy) was significantly lower than the disease progression group (p=0.03; Mann-Whitney test). The expression of hsa-miR-200c was significantly over-expressed in tumor tissues compare to normal tissues (p=0.0001; Wilcoxon test). Although hsa-let-7g is strongly associated with patient’s response to S-1 treatment, it is not a prognostic factor for predicting survival. Conclusion: hsa-let-7g and hsa-miR-200c may be associated with tumorigenesis in colon cancer. In addition, hsa-let-7g may be a significant indicator for chemoresponse to S-1 based chemotherapy. No significant financial relationships to disclose.

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Colorectal cancer (CRC) has high recurrence rate.Effective biomarkers for the detection of colon cancer are still unavailable. MicroRNA (miRNA) is an epigenetic factor that regulates cell proliferation, tumor cell growth, cancer formation, and metastasis by regulating tumor suppressor genes or oncogenes. miRNA has the potential to be used as a biomarker for the diagnosis of diverse cancers. Previously, we revealed that miR-139-3 p is downregulated and miR-338-5 p is upregulated in recurrent CRC patients. The present study further reveals that the miR-139-3 p expression level is inversely correlated with increased metastatic status in three colon cancer cell lines (SW480, SW620, and colo201), as determined using real-time polymerase chain reaction. Furthermore, in 51 pairs of CRC clinical specimens, the expression level of mir-139-3 p was significantly lower in the tumor sections than in the adjacent normal tissues (p < 0.0001), indicating that they are tumor-suppressive miRNAs. Furthermore, the expression level of mir-338-5 p in the tumor tissues of metastatic patients was significantly higher than in the tumor tissues of nonmetastatic patients (p < 0.05), indicating that mir-338-5 p is positively correlated with metastasis. All together, mir-139-3 p and mir-338-5 p

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