Association between TP53 genetic polymorphisms and the methylation and expression of miR-34a 34b/c in colorectal cancer tissues

摘要

Colorectal cancer (CRC) is one of the most common types of cancers, as evidenced by the >1.2 million patient diagnoses and 600,000 mortalities globally each year. Recently, the microRNA (miR/miRNA)-34 miRNA precursor family was revealed to participate in the tumor protein (TP)-53 pathway, which is frequently involved in CRC. Furthermore, the expression of miR-34 is reportedly regulated by DNA methylation. Accordingly, the present study investigated the correlation between the methylation status of miR-34 miRNAs and miR-34 expression in paired CRC tumor and normal tissues. The methylation status of miR-34a and miR-34b/c was determined using the MethyLight assay, and the expression of miR-34a and miR-34b/c in the same paired tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. The results revealed significantly elevated miR-34a (P=0.012) and miR-34b/c (P<0.0001) methylation levels in tumor tissues when compared with normal tissues, whereas only the expression of miR-34b/c differed (P=0.005) between the paired tissues. In addition, an association between TP53 haplotypes and miR-34 family expression levels was observed. The miR-34a methylation levels in the TP53 PIN A1A1 (48.56±36.49) and TP53 MSP GG (49.00±36.44) genotypes were increased in the tumor tissues when compared with normal tissues. In conclusion, it was determined that miR-34 promoter methylation and TP53 polymorphisms may be associated with CRC pathogenesis.