The polymorphic terminal-loop of pre-miR-1307 binding with MBNL1 contributes to colorectal carcinogenesis via...

Colorectal cancer (CRC) is one of the most common malignancies in the world. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in microRNA genes (miRSNPs) are involved in the occurrence of cancers. However, the relationship between the miRSNPs within the terminal-loops of microRNA precursors and the development of CRC is still largely unknown. In this study, we found that a miRSNP rs7911488 T>C in the terminal-loop of pre-miR-1307 was significantly associated with the occurrence of CRC. The C allele of rs7911488 is more prevalent in CRC patients than in healthy controls (P < 0.001), and this C allele prevalence is related to low level of miR-1307 expression. A RNA-binding protein MBNL1 binds with a 'UGCUGC' motif in the terminal-loop of the C-allelic pre-miR-1307 and blocks Dicer processing, resulting in downregulation of miR-1307 expression. Consequently, the antiapoptosis protein Bcl2, which is a direct target of miR-1307, is overexpressed in CRC. Furthermore, MBNL1 participates in processing of both C-allelic and T-allelic pre-miR-1307. In summary, our results show that rs7911488 C-allelic pre-miR-1307 binds to MBNL1 and infers with Dicer processing, leading to reduced miR-1307 and increased Bcl2 expression, thus representing an important process in the initiation of CRC.