Abstract
BackgroundBreast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified.MethodsThe levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis.ResultsHsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells.ConclusionHsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.
Highlights
Breast cancer (BC) is one of the major malignancies worldwide
Most studies have proven that Circular ribonucleic acid (RNA) (circRNA) act as sponges of microRNAs to further regulate the development of multiple human diseases [8, 12,13,14,15,16]
Tissue specimens A total of 50 pairs of BC tissues and matched normal tissues were collected from BC patients at The First Affiliated Hospital of China Medical University
Summary
Breast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Breast cancer (BC) is the second most common cancer worldwide and is a major cause of female death [1, 2] Some classical biomarkers, such as CEA and CA 15-3, Shi and Liu BMC Cancer (2021) 21:1249 molecular processes of BC to explore novel biomarkers for BC progression and therapeutic targets. Most studies have proven that circRNAs act as sponges of microRNAs (miRNAs) to further regulate the development of multiple human diseases [8, 12,13,14,15,16]. A novel circRNA, hsa_circ_0043278, was identified and found to be downregulated in BC tissues [19]. We predicted five putative target miRNAs. the underlying mechanisms of hsa_circ_0043278 remain to be elucidated. These findings prompted our interest in revealing the association between hsa_circ_0043278 and BC development
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