90P - The role of miR-133a-3p/SP1/IGF1R axis in the progression of colorectal cancer

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.