LncRNA GHET1 Promotes the Progression of Triple-Negative Breast Cancer via Regulation of miR-377-3p/GRSF1 Signaling Axis.

Abstract

Objective This study is aimed at investigating the role of lncRNA GHET1 in the progression of triple-negative breast cancer (TNBC). Methods Tumor tissues and paracancerous tissues (normal) of TNBC patients were collected. Human normal breast cells (MCF10A) and TNBC cells (MDA-MB-468 and HCC1937) were employed for in vitro analysis. The expression of lncRNA GHET1, miR-377-3p, and GRSF1 was detected by qRT-PCR. The lncRNA GHET1 and miR-377-3p were overexpressed or knocked down in the TNBC cells, respectively. To determine the specific biological activities of the TNBC cells, MTT, flow cytometry, and wound healing assay were adopted to evaluate the cellular proliferation, apoptosis, and migration abilities, respectively. MMP-9 and MMP-2 protein expression levels were detected as well by Western blot in the cells. The relationship between miR-377-3p and lncRNA GHET1, miR-377-3p, and GRSF1 was validated using dual-luciferase reporter assay. Results lncRNA GHET1 was significantly upregulated in the TNBC patients' tissues and the TNBC cell lines. Overexpression of lncRNA GHET1 significantly increased the proliferation and migration ability, but decreased apoptosis in the TNBC cells. Additionally, overexpression of lncRNA GHET1 upregulated both MMP-9 and MMP-2 protein expression levels. Correlation analysis found that miR-377-3p had a positive relationship with GRSF1, but had a negative relationship with lncRNA GHET1. miR-377-3p mimic attenuated the effects of lncRNA GHET1 on cellular proliferation, apoptosis, and migration of the TNBC cells. Conclusion lncRNA GHET1 promotes TNBC progression through the miR-377-3p/GRSF1 signaling axis.