miR-146a-5p targets interleukin-1 receptor-associated kinase 1 to inhibit the growth, migration, and invasion of breast cancer cells

Oncol Lett. 2019 Feb;17(2):1573-1580. doi: 10.3892/ol.2018.9769. Epub 2018 Nov 28.

Abstract

MicroRNAs (miRNAs) are associated with the formation and progression of many types of cancers. In the present study, the aim was to elucidate the involvement of miR-146a-5p in the regulation of human breast cancer (BC) cell growth and invasion, as well as the mechanisms underlying its effects. Reverse transcription-quantitative polymerase chain reaction results revealed that miR-146a-5p was markedly downregulated in BC tissues relative to those of adjacent normal tissues. miR-146a-5p expression was also markedly downregulated in BC cells. Overexpression of miR-146a-5p significantly suppressed the proliferation, invasion and migration of BC MDA-MB-453 and MCF7 cells. Furthermore, the results indicated that miR-146a-5p downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) by directly binding to its 3'-untranslated region in BC cells. Furthermore, IRAK1 expression was observed to be markedly upregulated and inversely correlated with miR-146a-5p expression in BC tissues. Mechanical studies indicated that restoring IRAK1 expression reversed the miR-146a-5p-induced inhibitory effects on proliferation and invasion of BC cells. In conclusion, miR-146a-5p may act as a tumor suppressor in BC by directly targeting IRAK1. These results highlighted the potential of miR-146a-5p as a novel therapeutic target for the treatment of BC.

Keywords: breast cancer; growth; interleukin-1 receptor-associated kinase 1; invasion; microRNA-146a-5p; migration.