MicroRNA-24 alleviates colorectal cancer progression via a rs28382740 single nucleotide polymorphism in the long noncoding region of X-linked inhibitor of apoptosis protein
Colorectal cancer (CRC) is one of the most prevalent malignant diseases worldwide. Recurrence correlates with the poor survival of patients with CRC. Targeted therapy and precision medicine for recurrent CRC may improve the clinical outcome. Therefore, finding biomolecules that can detect CRC early, assess its prognosis and survival, and predict its treatment response is key to improving the clinical prognosis. Here, we evaluated CRC recurrence by analyzing molecular differences using postoperative specimens. In the present study, whole-exome sequencing was first used to evaluate the molecular differences in CRC tissues from patients with recurrent disease, and the results were then verified with tissue array methods. The regulation of single nucleotide polymorphisms (SNPs) in long noncoding regions of interest was analyzed in the presence of target microRNAs via luciferase assays. The results showed that in patients with recurrent CRC, we mainly detected the G allele at the rs28382740 SNP in the 3'-untranslated region of the X-linked inhibitor of apoptosis (XIAP)-encoding gene. From the tissue arrays, up to 60% (3 of 5) of patients with the G allele at the rs28382740 SNP were diagnosed with CRC recurrence, while only 10% (1 of 10) of patients without the G allele had recurrent CRC (P = 0.039). Moreover, XIAP levels were high in non-CRC (50%, 2 of 4) and CRC (75%, 3 of 4) tissues of patients with recurrent disease and CRC (54.5%, 6 of 11) tissues of patients without recurrent disease, but only 9.1% (1 of 11) of non-CRC tissues of nonrecurrent patients expressed significantly high XIAP levels (P = 0.022). Using a luciferase assay, we found that miR-24s (miR-24-1-5p and miR-24-2-5p) targeting the rs28382740 SNP may reduce XIAP levels in CRC cells with rs28382740 SNP genotype G. These results indicated that apoptosis-related proteins, such as XIAP, may be therapeutic targets or biomarkers for tumor development. Our data support an inhibitory effect of miR-24s on XIAP expression. However, this inhibitory potency depends on the rs28382740 SNP genotype and may alleviate CRC progression by regulating the expression of XIAP.