The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1

Abstract

We previously discovered that rs7911488T>C in pre-miR-1307 was closely correlated to the risk of colorectal cancer (CRC). However, the roles of rs7911488 in CRC are still largely unknown. Here we explored the roles of rs7911488 in the growth and metastasis of CRC. We firstly generated cell lines SW480-T and SW480-C for stable expression of rs7911488 T-allelic and C-allelic pre-miR-1307, respectively. We subcutaneously grafted the cells into nude mice. We found that SW480-T tumors with high expression of miR-1307 obviously grew faster than the SW480-C tumors. Moreover, liver metastases (5/8) were observed in the mice bearing SW480-T tumors but not the SW480-C tumor-bearing mice. The results from colony formation assays, transwell assays, and wound healing assays demonstrated that the proliferative and metastatic abilities of SW480-T cells were evidently more potent than the SW480-C cells. Then we utilized gene array, real-time PCR, western blotting, and dual-luciferase reporter assays to figure out that miR-1307 directly inhibited PPRX1 expression by binding to its 3′-UTR. Thereafter, we confirmed that the proliferative and metastatic abilities of SW480 and HCT-116 cells were markedly enhanced by miR-1307, but were suppressed by PRRX1. Moreover, the regulatory roles of miR-1307 in the proliferation and metastasis of CRC cells were reversed by PRRX1. Notably, we also found that PRRX1 repressed CRC tumor growth in nude mice. In summary, our current study revealed that rs7911488-T allele led to over-expression of miR-1307, which inhibited PRRX1 and consequently promoted the proliferation and migration of CRC cells. This might offer a novel insight into the progression of CRC.