Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. MicroRNA has been reported playing an important role in a variety of cancers including colorectal cancer.
CRC tissues as well as CRC cell lineswere used to evalute the expression and function of miR-133a-3p, SP1 and IGF1R. The relationship between miR-133a-3p and clinical-pathological charateristics of CRC patients were analyzed. The interaction among miR-133a-3p/SP1/IGF1R was assessed using Dual Luciferase reporter.
MiR-133a-3p has been found down-regulated in CRC tissues compared with the adjacent normal tissues. The expression of miR-133a-3p was significantly associated with histological differentiation (P=0.01) and TNM stage (P=0.006) respectively. CRC patients with low miR-133a-3p expression had a significantly shorter survival time than those patients with high miR-133a-3p expression (P=0.04). Gain-of-function assays showed that miR-133a-3p inhibited cellular proliferation and colony formation, but had no effect on migration and invasion of CRC cells. Furthermore, expression of SP1 and IGF1R was reduced by elevating miR-133a-3p expression in CRC cells. Luciferase assay further confirmed that SP1 but not IGF1R was the target gene of miR-133-3p and SP1 could bind to the promoter region of IGF1R gene.
In summary, our findings first demonstrate that miR-133a-3p acts as a tumor suppressor by targeting SP1 and miR-133a-3p/SP1/IGF1R signaling pathway is involved in CRC progression. MiR-133a-3p may be a novel molecular therapeutic target for CRC.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.