A Novel miRNA Located in the HER2 Gene Shows an Inhibitory Effect on Wnt Signaling and Cell Cycle Progression

Abstract

Human epidermal growth factor receptor 2 (HER2) is involved in the development of the majority of cancers. Therefore, it can be a potential target for cancer therapy. It was hypothesized that some of the broad effects of HER2 could be mediated by miRNAs that are probably embedded inside this gene. Here, we predicted and then empirically substantiated the processing and expression of a novel miRNA named HER2-miR1, located in the HER2 gene; transfection of a DNA fragment corresponding to HER2-miR1 precursor sequence (preHER2-miR1) resulted in ~4000-fold elevation of HER2-miR1 mature form in HEK293t cells. Also, the detection of HER2-miR1 in 5637, NT2, and HeLa cell lines confirmed its endogenous production. Following the HER2-miR1 overexpression, TOP/FOP flash assay and RT-qPCR results showed that Wnt signaling pathway was downregulated. Consistently, flow cytometry results revealed that overexpression of HER2-miR1 in Wnt+ cell lines (SW480 and HCT116) was ended in G1 arrest, unlike in Wnt- cells (HEK293t). Taking everything into account, our results report the discovery of a novel miRNA that is located within the HER2 gene sequence and has a repressive impact on the Wnt signaling pathway.