Long non‐coding RNA (lncRNA) is involved in the regulation of tumorigenesis and metastasis. In this study, we focused on the clinical relevance, biological effects, and molecular mechanisms of the lncRNA differentiation antagonizing non‐protein coding RNA (DANCR) in breast cancer. We compared the expression of DANCR between breast cancer and normal tissues, and between breast cancer cell lines and normal breast epithelial cells using quantitative real‐time PCR (qRT‐PCR) analysis. By knocking down and overexpressing DANCR, we assessed its significance in regulating viability (MTT assay), migration/invasion (Transwell assay), epithelial‐mesenchymal transition (western blot), stemness (mammosphere formation assay and western blot), and production of inflammatory cytokines (qRT‐PCR and ELISA) of breast cancer cells in vitro, as well as xenograft growth in vivo. Furthermore, using ChIP and RNA immunoprecipitation, we examined the reciprocal regulation between DANCR and suppressor of cytokine signaling 3 (SOCS3) in breast cancer. DANCR was significantly up‐regulated in tissue samples from patients with breast cancer, as well as in breast cancer cell lines, as compared with normal tissues and breast epithelial cells, respectively. The highest DANCR expression levels were associated with advanced tumor grades or lymph node metastasis. DANCR was necessary and sufficient to control multiple malignant phenotypes of breast cancer cells in vitro and xenograft growth in vivo. Mechanistically, DANCR promoted the binding of enhancer of zeste homolog 2 (EZH2) to the promoter of SOCS3, thereby epigenetically inhibiting SOCS3 expression. Functionally, SOCS3 up‐regulation or EZH2 inhibition could rescue multiple malignant phenotypes induced by DANCR. Our data indicate that DANCR is a pleiotropic oncogenic lncRNA in breast cancer. Boosting SOCS3 expression may reverse the oncogenic activities of DANCR and thus provide a therapeutic strategy for breast cancer treatment.

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The application of magnetic fluid hyperthermia (MFH) with nanoparticles has been shown to inhibit tumor growth in several animal models. However, the feasibility of using MFH in vivo to treat breast cancer is uncertain, and the mechanism is unclear. In the present study, it was observed that the intratumoral administration of MFH induced hyperthermia significantly in rats with Walker-265 breast carcinomas. The hyperthermia treatment with magnetic nanoparticles inhibited tumor growth in vivo and promoted the survival of the tumor-bearing rats. Furthermore, it was found that MFH treatment downregulated the protein expression of vascular endothelial growth factor (VEGF) in the tumor tissue, as observed by immunohistochemistry. MFH treatment also decreased the gene expression of VEGF and its receptors, VEGF receptor 1 and 2, and inhibited angiogenesis in the tumor tissues. Taken together, these results indicate that the application of MFH with nanoparticles is feasible for the treatment of breast carcinoma. The MFH-induced downregulation of angiogenesis may also contribute to the induction of an anti-tumor effect.

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