STAT3-induced HLA-F-AS1 promotes cell proliferation and stemness characteristics in triple negative breast cancer cells by upregulating TRABD

Abstract

Breast cancer (BC) is one of the most common malignances and is a leading cause of cancer-related deaths in women globally. Triple negative breast cancer (TNBC) is a common subtype of BC. Emerging evidence has indicated the crucial roles of long noncoding RNAs (lncRNAs) in the tumorigenesis of TNBC. Our aim was to explore the role and regulatory mechanism of lncRNA HLA-F antisense RNA 1 (HLA-F-AS1) in TNBC cells. Cell counting kit‐8 (CCK-8) assay, colony formation assay, flow cytometry analysis and western blot analysis were used to measure HLA-F-AS1-mediated cellular behaviors in TNBC. Xenograft tumor assay was applied to assess biological function of HLA-F-AS1 in vivo. Luciferase reporter assay and RNA pull down assay were used to verify the binding ability between molecules. Our findings demonstrated that HLA-F-AS1 expression was significantly upregulated in TNBC tissues and cells, and high level of HLA-F-AS1 indicated the poor prognosis of patients with TNBC. HLA-F-AS1 promoted TNBC progression by facilitating cell proliferation and stemness maintenance and inhibiting cell cycle arrest at G0/G1 stage and apoptosis in vitro as well as inducing tumor growth in vivo. HLA-F-AS1. In addition, signal transducer and activator of transcription 3 (STAT3) transcriptionally induced HLA-F-AS1 upregulation in TNBC cells via interacting with HLA-F-AS1 promoter. Moreover, HLA-F-AS1 acted as the molecular sponge of microRNA 541-3p (miR-541-3p) to elevate TRABD (TraB domain containing) expression in TNBC cells. Rescue experiments confirmed that the decrease of cell proliferation and stemness characteristics under silenced HLA-F-AS1 was rescued by TRABD overexpression in TNBC cells. In conclusion, STAT3-induced HLA-F-AS1 facilitates cell proliferation and stemness characteristics in TNBC by miR-541-3p-dependent upregulation of TRABD, which might provide a potential novel direction for the treatment of TNBC.