Low microRNA150 expression is associated with activated carcinogenic pathways and a poor prognosis in patients with breast cancer

Abstract

Breast cancer is the most common type of cancer amongst women worldwide, and numerous microRNAs (miRNAs/miRs) are involved in the initiation and progression of breast cancer. The aim of the present study was to identify hub miRNAs and determine the underlying mechanisms regulated by these miRNAs in breast cancer. Breast invasive carcinoma transcriptome data (including mRNAs and miRNAs), and clinical data were acquired from The Cancer Genome Atlas database. Differential gene expression analysis, co‑expression network analysis, gene set enrichment analysis (GSEA) and prognosis analysis were used to screen the hub miRNAs and explore their functions. Functional experiments were used to determine the underlying mechanisms of the hub miRNAs in breast cancer cells. The results revealed that low miR150 expression predicted a more advanced disease stage, and was associated with a less favorable prognosis. Through the combined use of five miRNA‑target gene prediction tools, 31 potential miR150 target genes were identified. GSEA revealed that low miR150 expression was associated with the upregulation of several cancer‑associated signaling pathways, and the downregulation of several tumor suppressor genes. Furthermore, miR150 independently affected overall survival in patients, and interacted with its target genes to indirectly affect overall and disease‑free survival. Functional experiments demonstrated that miR150 positively regulated B and T lymphocyte attenuator (BTLA), and the downregulation of miR150 and BTLA combined promoted cell migration. In conclusion, the present study revealed that low miR150 expression was associated with less favorable clinical features, upregulation of several carcinogenic signaling pathways, and poor patient survival. Additionally, a miR150‑BTLA axis was suggested to regulate cell viability and migration.

Keywords: breast cancer,; prognosis; microRNA150; B and T lymphocyte attenuator; cell migration.