KRAS Up-regulates the Expression of miR-181a, miR-200c and miR-210 in a Three-dimensional-specific Manner in DLD-1 Colorectal Cancer Cells

Background: We previously found that oncogenic KRAS induces increased expression of microRNAs (miRNAs), such as miR-200c and miR-221/222, in human colorectal cancer (CRC) HCT116 cells in a three-dimensional (3D)- specific manner, however, the regulation of miRNA expression through oncogenic KRAS in other types of CRC remains unclear. Materials and Methods: The differential expression of 94 cancer-related miRNAs was examined in DLD-1 and DKO-4 cells (DLD-1 cells with a disrupted oncogenic KRAS) in 3D cultures. Results: Increased miR-15b, miR-16, miR- 23a, miR-24, miR-103 and miR-222 expression was observed in 3D and in 2D cultures. Of note, increased miR-181a, miR- 200c and miR-210 expression was only observed in 3D cultures. Furthermore, miR-181a and miR-210 were significantly overexpressed in DLD-1 cells in 3D culture compared with those in HCT116 cells, and were significantly overexpressed in human CRC specimens. Conclusion: Oncogenic KRAS regulates 3D-specific miRNAs that are possibly associated with CRC development in vivo.