Differential MicroRNA Expression Profile of Colon Cancer Stem Cells Derived from Primary Tumor and HT-29 Cell line

Background: Colorectal cancer (CRC) is one of the most prevalent cancers in the world. Cancer stem cells (CSC) have been reported in many human tumors and are thought to be responsible for tumor initiation, therapy resistance, progression, relapse, and metastasis. Recent studies revealed that microRNAs (miRNA) play important roles in maintaining stemness of embryonic stem cells and CSCs. Objectives: With regard to the crucial role of cancer stem cells in colon cancer initiation and maintenance, the miRNA expression profile in primary and cell line cancer stem cells compared to non-stem cells cancer cells were evaluated. Methods: In this study, a population of colon CSCs from primary colon cancer and human HT-29 colonic adenocarcinoma cell line was isolated from serum free medium and their microRNA profiles were evaluated using miRNA PCR array. Results: The isolated cells with high expression of EPCAM+/CD44+ markers showed greater colony-forming efficiency and higher tumorigenic potential. Furthermore, expression of “stemness” genes including C-myc, Klf4, Nanog, Sox2 and Oct4 was higher in isolated cancer stem cells. Moreover, miRNA expression profile of colon CSCs was performed using miRNA PCR array. There are 39 differentially expressed miRNAs, 24 of which had lower mean expression in the cancer stem cells samples. By contrast, 15 miRNAs had higher expression levels in CSCs samples. Of these, miR-495, miR-125, and miR-199a were the most significantly up-regulated miRNAs. Conclusions: Our results suggest that miRNAs might play important roles in maintenance and regulation of colon CSCs and specific miRNA expression signatures may contribute to cancer initiation and expansion.