Abstract 3042: Investigating microRNA expression profiles in colon cancer cells in response to cyclooxygenase 2 signaling

Abstract

Abstract MicroRNAs (miRNAs) are emerging as central players in cancer progression. Aberrant expression of miRNAs leads to malignant transformation and correlates with staging, progression and prognosis of cancers. Unfortunately, signaling pathways leading to altered expression of miRNAs are largely unknown. During early development of colon cancer, the expression of cyclooxygenase 2 (COX-2) is constitutively induced. We and others have shown that constitutive expression of COX-2 promotes colon carcinogenesis. However, the underlying mechanisms are not completely understood. To determine if COX-2 signaling alters expression of miRNAs, we used the Human Cancer RT2-miRNA PCR arrays to profile miRNA expression in HCA-7 human colon cancer cells treated with or without the COX-2 selective inhibitor NS-398. HCA-7 cells constitutively express endogenous COX-2. We found that expression levels of 39 miRNAs are different in HCA-7 cells as compared to HCA-7 cells treated with NS-398; 8 miRNAs were up-regulated and 31 miRNAs were down-regulated. To confirm the data from the PCR array, we used quantitative RT-PCR to quantify expression of 8 miRNAs in HCA-7 cells with or without NS-398 treatment. These 8 miRNAs were selected due to their relevance to cancer invasion and metastasis. We also compared the expression of these miRNAs in HCT-15 human colon cancer cells that were engineered to stably express COX-2 (HCT-15-COX-2) to the parental HCT-15 cells. Expression levels of 6 of the 8 examined miRNAs (miR-23b, 124, 146b-5p, 155, 183, 184) were significantly lower in HCT-15-COX-2 or HCA-7 cells than in parental HCT-15 or HCA-7 cells that were treated with NS-398. Therefore, we identified 6 miRNAs that are modulated by COX-2 and may play a role in mediating COX-2 signaling to promote colon carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3042.