Breast cancer is one of the most common malignancies and a major cause of cancer-related mortality all over the world. A growing body of reports revealed that microRNAs play essential roles in the progression of cancers. Aberrant expression of miR-503 has been reported in several kinds of cancer. The aim of the current study was to elucidate the role of miR-503 in the pathogenesis of breast cancer. In the present study, our results suggested that miR-503 expression was markedly downregulated in breast cancer tissues and cells. Overexpression of miR-503 in breast cancer cell lines reduced cell proliferation through inducing G0/G1 cell cycle arrest by targeting CCND1. Together, our findings provide new knowledge regarding the role of miR-503 in the progression of breast cancer and indicate the role of miR-503 as a tumor suppressor microRNA (miRNA) in breast cancer.

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Background: This study aimed to explore the potentially predictive role and dynamic changes of immune checkpoints on T cell subsets in patients with breast cancer receiving neoadjuvant chemotherapies. Methods: Fluorescent multiplex immunohistochemistry (mIHC) was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in paired breast cancer samples before and after neoadjuvant therapies (NAT) in a prospective cohort (n = 50). Singleplex IHC was conducted to stain for CD3 in 100 cases with inclusion of extra retrospective 50 cases. Cell levels were correlated with clinicopathological parameters and pathological complete response (pCR). Results: In pretreatment tumors, the percentages of infiltrating CD8 + , PD1 + , PD1 + CD8 + , and the ratio of PD1 + CD8 + /CD8 + cells, were higher in pCR than non-pCR patients in either the stromal or intratumoral area, but PD1 + CD4 + , TIM3 + CD4 + , TIM3 + CD8 + cells and CD4 + /CD8 + ratio was not. Multivariate analyses showed that the percentage of intratumoral CD8 + cells (OR, 1.712; 95% CI: 1.052-2.786; P = 0.030) and stromal PD1 + CD8 + /CD8 + ratio (OR, 1.109; 95% CI: 1.009-1.218; P = 0.032) were significantly associated with pCR. Dynamically, reduction in the percentages of PD1 + , CD8 + and PD1 + CD8 + cells after therapy strongly correlated with pCR. Notably, incremental percentages of PD1 + CD8 + cells, rather than TIM3 + CD8 + , were shown in tumors from non-pCR patients after NAT. CD3 staining confirmed the percentage of T cells were associated with pCR. Conclusions: PD1 + CD8 + rather than TIM3 + CD8 + cells are main predictive components within tumor-infiltrating T cells in NAT breast cancer patients. Dynamically incremental levels of PD1 + CD8 + cells occurred in non-pCR cases after NAT, suggesting the combination of chemotherapy with PD1 inhibition might benefit these patients.

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Breast cancer (BC) is a common cancer and leading cause of cancer-associated mortality in women. Abnormal expression of long non-coding RNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was associated with the development of a number of tumors. However, whether FOXD2-AS1 is dysregulated in BC and its underlying mechanisms remain unclear. In the present study, it was identified that FOXD2-AS1 expression was upregulated in BC tissue, cell lines and sphere subpopulation. Additionally, the abnormal upregulation of FOXD2-AS1 predicted poor prognosis in patients with BC. Furthermore, downregulation of FOXD2-AS1 decreased cell proliferation, and migratory and invasive abilities in BC cells, and decreased the growth of transplanted tumors in vivo. Downregulation of FOXD2-AS1 decreased the percentage of CD44 antigen + /signal transducer CD24in breast cancer stem cell (BCSC) cells, and decreased the expression of numerous stem factors, including Nanog, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (SOX2), and inhibited the epithelial-mesenchymal transition process. FOXD2-AS1 was identified to be primarily located in the cytoplasm. Using bioinformatics analysis, a reporter gene assay and reverse transcription-polymerase chain reaction assays, it was demonstrated that microRNA (miR)-150-5p was able to bind directly with the 3'-untranslated region of FOXD2-AS1 and PFN2 mRNA. miR-150-5p mimics decreased the cell proliferation, migration and invasion of BC cells. FOXD2-AS1 knockdown significantly inhibited the miR-150-5p inhibitor-induced increase in Nanog, Oct4 and SOX2 expression. The miR-150-5p inhibitor-induced increase in N-cadherin, and decrease in E-cadherin and vimentin was inhibited by FOXD2-AS1 knockdown. Profilin 2 (PFN2) expression was significantly upregulated in BC tissues. Additionally, the abnormal upregulation of PFN2 was associated with poor prognosis in patients with BC. FOXD2-AS1 and PFN2 expression was positively correlated. Collectively, the present results demonstrated the role of the FOXD2-AS1/miR-150-5p/PFN2 axis in the development of BC, and provides novel targets for the treatment of BC, and potential biomarkers for diagnosis and prognosis of BC.