Background
A number of microRNAs (miRNAs) have been demonstrated to be correlated with the diagnosis, progression and prognosis of colorectal cancer (CRC). However, the key miRNAs and the associated signaling pathways that regulate the growth and metastasis of CRC remain unclear.
Methods
miRNA array was analyzed in CRC CT26 cell-transplanted BALB/c mice. The effects of miR-762 mimics and inhibitors on the growth, invasion, cell cycle, and regulatory pathways of CRC CT26 cells were assessed. Cell cycle and sub-G1 assay were collected from the treated CT26 cells. Finally, blood samples were collected from patients with CRC. Further analysis to compare miR-762 levels in blood samples collected from CRC patients and normal control donors. Patients’ basic data were retrieved from electronic medical records and analyzed for age, gender, tumor staging, and survival.
Results
The miRNA levels in mice with CRC cell implantation indicated that plasma mmu-miR-762 was upregulated. Transfection of mmu-miR-762 mimic to CT26 cells increased cell viability, invasion, and EMT, whereas transfection of mmu-miR-762 inhibitor decreased the above abilities. Cells treated with high-concentration mmu-miR-762 inhibitor induced cell cycle arrest at G0/G1 phase. However, mmu-miR-762 did not cause apoptosis of cells. Western blot analysis showed that mmu-miR-762 mimic transfection upregulated the expression of Wnt-1 and β-catenin, as well as increased the nuclear translocation of β-catenin. Further analysis was performed to demonstrate the correlation of has-miR-762 with CRC, and blood samples were collected from CRC patients and control donors. The results showed that serum has-miR-762 levels in CRC patients were higher than in control donors. Among the CRC patients, patients with distant metastasis showed higher serum has-miR-762 levels than patients without distant metastasis.
Conclusions
The present study demonstrated that circulating miR-762 might be a biomarker with upregulation of CRC cell growth and invasion through the Wnt/β-catenin signaling.