Selection and characterization of novel DNA aptamers targeting colorectal cancer cells with malignant potential

Colorectal cancer (CRC) is associated with high morbidity and mortality rates worldwide. Therefore, early diagnosis and treatment are of great significance for improving the survival rate of CRC patients. Herein, we performed subtractive cell-SELEX using two cell lines (LS174T and CL187) with the same genetic background but different malignant potentials for the target and negative cells. Two aptamers LS1 and LS52 showed high affinity with target LS174T cells and high specificity for CRC cells with malignant potential, and exhibited good biological stability. In addition, we found that aptamer LS1 had the effect of promoting in vitro proliferation and monoclonal formation of CRC cells, and upregulated the expression of proliferation related proteins. Based on the high affinity of aptamer LS52, using LS52 as a molecular probe could effectively distinguish clinical CRC tissues and adjacent normal tissues, CRC metastatic tissues and non-metastatic tissues. Analysis of protein expression in magnetic bead sorted cells showed that the expression of malignant potential related proteins in LS52^high cells was higher than that in LS52^low cells. Finally, a cell membrane protein SRSF6 was identified as the target of aptamer LS52, which may serve as a new molecular target for CRC. Therefore, our work provides a systematic novel approach of studying potential biomarkers and a promising tool for cancer diagnosis and therapy.

Graphical Abstract