Abstract 3979: Identification of microRNA 885-5p as a novel regulator of tumor metastasis in colorectal cancer

Abstract

Abstract Introduction: MicroRNAs (miRNAs) are a class of small non-coding RNAs that play a crucial role in cellular proliferation, differentiation and apoptosis by regulating gene expression. They are involved in the regulation of human diseases as well as colorectal cancer (CRC). CRC is the third most common cancer in the world and second leading cause of cancer death in the Hong Kong. Liver is the most common site of distant metastasis with poor prognosis for CRC patients. Recent evidences suggested that miRNAs affect the cell invasiveness of various cancers and regulate key steps in metastatic cascade. Moreover, studies also demonstrated that miRNAs play critical roles in the regulation of drug resistance. The study of miRNAs mechanism in liver metastasis may provide some new strategies for cancer treatment. Method: Microarrays were used for screening the expression differences of miRNAs between normal colon, CRC and liver metastasis. Lentiviral transduced colon cell lines were sorted with flow cytometer high-speed sorter by green fluorescent protein signal. Functional assay such as wound healing and invasion chamber were used to study the metastatic property (migration and invasion) in vitro. GeneChip expression was used to study the mRNA expression differences between gain-of-function and control. Orthotopic implantation of mi-885-5p-expressing CRC cells into the cecal wall of nude mice was performed to investigate their tumorigenic and metastatic capacity in vivo. Results: We quantified the expression levels of miRNAs in 14 liver metastasis samples and 12 colorectal cancer tissues, and identified hsa-miR-885-5p whose expression levels were significantly up-regulated in liver metastasis samples compared with the CRC samples. Over-expressed miR-885-5p cell line showed more invasive and migratory when comparing with control. 67% of the mice developed liver metastasis with orthotopic implantation of a CRC cell line overexpressing miR-885-5p, as compared with 33% of metastatic incidence in mice injected with the vector-expressing CRC cell line. GeneChip array showed that VCAM1 may be one of a possible target of miR-885-5p, which was comparable with the online database. Conclusion: We conclude that over expression of miR-885-5p is observed in liver metastasis has an important role in regulating the metastatic capacity of CRC cells vitro and in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3979. doi:10.1158/1538-7445.AM2011-3979