Androgen receptor (AR) is closely associated with the occurrence and progression of breast cancer; however, the clinical significance of it in triple negative breast cancer (TNBC) has been controversial. There is a limited amount of research regarding the effect of neoadjuvant chemotherapy on AR expression. By examining the expression of AR in patients with TNBC, the aim of the present study is to explore the clinical significance of AR and provide evidence for AR-directed treatment in TNBC. A total of 188 patients with primary TNBC with complete medical records were included in this retrospective study. Tumor sections from 41 patients (21.8%) were positive for AR, which was more often detected in small tumors (P=0.042) and cases with no lymph node involvement (P=0.032). Among them, 102 were treated with neoadjuvant chemotherapy (NAC). A total of 17 patients (16.7%) exhibited pathological complete response. However, the patient response was irrelevant to AR expression. Matched pathological tissues before and after NAC were collected for 49 cases, suggesting an enrichment of AR-expressing tumors following chemotherapy (P=0.008). Further analysis indicated that AR expression had no correlation with the disease-free and overall survival of patients with general TNBC; rather, it predicted a poor survival of the patients with stage III TNBC in comparison with those at earlier stages (P=0.035). AR expression occurs more often in small TNBC tumors or in cases with no lymph node metastasis. It is associated with a poor prognosis of the patients with advanced stages of tumors.

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.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a high degree of malignancy. TNBC is prone to distant metastasis and has a poor prognosis. A number of TNBC-related microRNAs (miRNAs) have been studied and identified. However, the detailed roles of miR-574-5p in TNBC remain poorly understood. miR-574-5p, SRY (sex determining region Y)-box 2 (SOX2), B-cell lymphoma/leukaemia 11A (BCL11A), SKI like proto-oncogene (SKIL) and epithelial-mesenchymal transition (EMT)-related miRNAs and proteins were measured by reverse transcription-quantitative PCR and western blotting analysis, respectively. A luciferase reporter assay was employed to validate the direct targeting of SOX2 and BCL11A by miR-574-5p. MTT, colony formation and Transwell assays were performed to analyse the biological functions of miR-574-5p in TNBC cells. A nude mouse xenograft model was used to verify the effects of miR-574-5p on the tumorigenesis of TNBC in vivo. The results demonstrated that miR-574-5p levels were decreased in breast cancer tissues and cells. miR-574-5p repressed proliferation, migration and EMT in TNBC cells. Further experiments confirmed that miR-574-5p reduced tumour size and metastasis in vivo. miR-574-5p targeted BCL11A and SOX2 to inhibit the SKIL/transcriptional co-activator with PDZ-binding motif/connective tissue growth factor axis, and the inhibitory effect of miR-574-5p in TNBC cells was at least partly dependent on SOX2 and BCL11A. In addition, the regulation of downstream oncogenes by SOX2 was dependent on BCL11A. To the best of our knowledge, this is the first study to report the association between the miR-574-5p/BCL11A/SOX2 axis and the tumorigenesis of TNBC, which provides a new mechanism for understanding the progression of TNBC.