Abstract 5403: Discovery of high metastatic potential microRNAs in human colorectal cancer

Abstract

Abstract Background and Aim: Colorectal cancer (CRC) is the third most common cancer worldwide. More than half of the CRC patients have liver metastasis at the time of diagnosis, which is the major cause of cancer-related death in CRC. MicroRNAs (miRNAs) have been identified as modulators of the epithelial-mesenchymal transition (EMT)-mesenchymal to epithelial transition (MET) process by regulating transcription factors. However, it is not clear which specific miRNAs are critical drivers of CRC metastasis development. The aim of this study was to discovery novel high metastatic potential miRNAs in matched CRC and metastasis tissues, serum-exosome, and CRC cells with high metastasis property. Materials and Methods: We isolated total RNAs from pairs of normal colon (NC), primary CRC (pCRC), liver metastasis (LM), normal liver (NL) tissue specimens, and pre-OP/post-OP serum-exosome sample from 15 each CRC patients. We also prepared total RNAs from 4 CRC cell lines (SW480, LS174T, COLO 205, and EMT-induced SW480) as well as exosome from their culture medium. To induce EMT process, epithelial phenotype CRC cell (SW480) was treated with epidermal growth factor (EGF). Next, miRNAs discovery step was conducted via NanoString analysis. Further miRNAs expression was determined by quantitative real-time PCR (qRT-PCR), and miRNAs expression was normalized relative to U6 and cel-miR-39 expression for tissue and serum-exosome samples, respectively. Results: We successfully generated miRNAs expression profiles to distinguish NC vs. pCRC, pCRC vs. LM, LM vs. NL, and epithelial phenotype cells vs. high metastatic phenotype cells. Interestingly, a subset of miRNAs, including miRNA-100-5p, -339-3p, -549a, -1304-5p, and -1972, was commonly enhanced in LM, EMT-induced SW480, and high metastatic phenotype CRC cells compared to pCRC, SW480, and low metastatic phenotype CRC cells. In our further miRNAs validation analysis using pairs of pCRC and LM tissues from 15 CRC patients, miRNA-100-5p (P<0.0001), miR-339-3p (P=0.0022), and miR-1972 (P<0.0001) were significantly upregulated in pCRC than matched LM tissues. We also observed discordance expression patterns of miRNAs between CRC tissues and serum-exosome specimens. Conclusions: Our findings suggest that a unique subset of miRNAs is involved in CRC metastasis development, which may associate with EMT process and acquiring of high metastatic potential in CRC cells. Moreover, our metastasis specific miRNAs profile might be useful for development of markers predicting and/or treatment of CRC patients with metastasis. Citation Format: Jee Hyun Lee, Gyeonghwa Kim, Hye Jin Kim, Gyu-Seog Choi, Keun Hur. Discovery of high metastatic potential microRNAs in human colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5403.