Abstract: Objective To investigate the effection of miR-146a and its target gene EGFR on the migration of breast cancer cells. Methods Recombinant soluble TRAIL (rsTRAIL) was used at a final concentration of 50, 100, 200, and 500 μg /L to continually stimulate TRAIL-sensitive MDA-MB-231 cells for four weeks, respectively, and a TRAIL-insensitive breast cancer cell line named MDA-MB-231/TR was screened. MiR-146a expression level was evaluated using RT-PCR. Transwell cell invasion assay and wound-healing experiment were performed to examine the migration of breast cancer cells. The relationship between miR-146a level and EGFR expression was identified in MDA-MB-231/TR cells by dual luciferase reporter assay and Western blot. The expression of DR4, DR5, IRAK1, CXCR4, p-IκBα and apoptosis-related proteins were detected by Western blot. Chromatin immunoprecipitation(ChIP) analysis revealed the binding activity of NF-κB p65 subunit to the binding sites of miR-146a promoter element in MDA-MB-231/TR cells. Result MiR-146a expression in a TRAIL-insensitive breast cancer cell line MDA-MB-231/TR was decreased significantly. Down-regulation of miR-146a increased its target EGFR expression, and eventually promoted breast cancer cell migration. Furthermore, we found that NF-κB regulated the low expression of miR-146a in the MDA-MB-231/TR cells. Conclusion miR-146a plays an important regulatory role in the migration of TRAIL-insensitive breast cancer cells.

Key words: Key words: TRAIL, breast cancer cells, miR-146a, migration