Breast cancer angiogenesis is key for metastasis and predicts a poor prognosis. Angiotensin-converting enzyme 2 (ACE2), as a member of the renin-angiotensin system (RAS), was reported to restrain the progression of hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) through inhibiting angiogenesis. However, the relationship between ACE2 and breast cancer angiogenesis remains unclear. The prognosis and relative gene selection were analysed using the GEPIA, GEO, TCGA and STRING databases. ACE2 expression in breast cancer tissue was estimated by reverse transcription-quantitative polymerase chain reaction (qPCR). Breast cancer cell migration, proliferation and angiogenesis were assessed by Transwell migration, proliferation, tube formation, and wound healing assays. The expression of vascular endothelial growth factor A (VEGFa) was detected by qPCR and Western blotting. The phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated protein kinase 1/2 (ERK1/2) was examined by Western blotting. Breast cancer metastasis and angiogenesis in vivo were measured using a zebrafish model. ACE2 was downregulated in breast cancer patients. Patients with higher ACE2 expression had longer relapse-free survival (RFS). In vitro, ACE2 inhibited breast cancer migration. Meanwhile, ACE2 in breast cancer cells inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, tube formation and migration. In the zebrafish model, ACE2 inhibited breast cancer cell metastasis, as demonstrated by analyses of the number of disseminated foci and the metastatic distance. Neo-angiogenesis was also decreased by ACE2. ACE2 downregulated the expression of VEGFa in breast cancer cells. Furthermore, ACE2 in breast cancer cells inactivated the phosphorylation of VEGFR2, MEK1/2, and ERK1/2 in HUVECs. Our findings suggest that ACE2, as a potential resister to breast cancer, might inhibit breast cancer angiogenesis through the VEGFa/VEGFR2/ERK pathway. Retrospectively registered.

Background: Kinesin superfamily (KIFs) has a long-reported significant influence on the initiation, development, and progress of breast cancer. However, the prognostic value of whole family members was poorly done. Our study intends to demonstrate the value of kinesin superfamily members as prognostic biomarkers as well as a therapeutic target of breast cancer.Methods: Comprehensive bioinformatics analyses were done using data from TCGA, GEO, METABRIC, and GTEx. LASSO regression was done to select tumor-related members. Nomogram was constructed to predict the overall survival (OS) of breast cancer patients. Expression profiles were testified by quantitative RT-PCR and immunohistochemistry. Transcription factor, GO and KEGG enrichments were done to explore regulatory mechanism and functions.Results: A total of 20 differentially expressed KIFs were identified between breast cancer and normal tissue with 4 (KIF17, KIF26A, KIF7, KIFC3) downregulated and 16 (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF20B, KIF22, KIF23, KIF24, KIF26B, KIF2C, KIF3B, KIF4A, KIFC1) overexpressed. Among which, 11 overexpressed KIFs (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF23, KIF2C, KIF4A, KIFC1) significantly correlated with worse OS, relapse-free survival (RFS) and distant metastasis-free survival (DMFS) of breast cancer. A 6-KIFs-based risk score (KIF10, KIF15, KIF18A, KIF18B, KIF20A, KIF4A) was generated by LASSO regression with a nomogram validated an accurate predictive efficacy. Both mRNA and protein expression of KIFs are experimentally demonstrated upregulated in breast cancer patients. Msh Homeobox 1 (MSX1) was identified as transcription factors of KIFs in breast cancer. GO and KEGG enrichments revealed functions and pathways affected in breast cancer.Conclusion: Overexpression of tumor-related KIFs correlate with worse outcomes of breast cancer patients and can work as potential prognostic biomarkers.

Long non‐coding RNAs (lncRNAs) take various effects in cancer mostly through sponging with microRNAs (miRNAs). lncRNA NR2F1‐AS1 is found to promote tumour progression in hepatocellular carcinoma, endometrial cancer and thyroid cancer. However, the role of lncRNA NR2F1‐AS1 in breast cancer angiogenesis remains unknown. In this study, we found lncRNA NR2F1‐AS1 was positively related with CD31 and CD34 in breast cancer through Pearson's correlation analysis, while lncRNA NR2F1‐AS1 transfection promoted human umbilical vascular endothelial cell (HUVEC) tube formation. In breast cancer cells, lncRNA NR2F1‐AS1 enhanced the HUVEC proliferation, tube formation and migration ability through tumour‐conditioned medium (TCM). In zebrafish model, lncRNA NR2F1‐AS1 increased the breast cancer cell‐related neo‐vasculature and subsequently promoted the breast cancer cell metastasis. In mouse model, lncRNA NR2F1‐AS1 promoted the tumour vessel formation, increased the micro vessel density (MVD) and then induced the growth of primary tumour. Mechanically, lncRNA NR2F1‐AS1 increased insulin‐like growth factor‐1 (IGF‐1) expression through sponging miRNA‐338‐3p in breast cancer cells and then activated the receptor of IGF‐1 (IGF‐1R) and extracellular signal‐regulated kinase (ERK) pathway in HUVECs. These results indicated that lncRNA NR2F1‐AS1 could promote breast cancer angiogenesis through IGF‐1/IGF‐1R/ERK pathway.

Breast cancer (BC) is one of the most common female cancers, and its incidence has been increasing in recent years. Although treatments are continuously improving, the prognosis of patients in the advanced stage is still unsatisfactory. Thus, an in-depth understanding of its molecular mechanisms is necessary for curing breast cancer. KIF15 is a tetrameric spindle motor which can regulate mitosis in cellular process and exert the crucial functions in several cancers. The purpose of our research was to investigate the functions of KIF15 in breast cancer. We tested the expression of KIF15 in breast cancer tissues and the survival rate of breast cancer patients with high or low level of KIF15 through TCGA data. What's more, western blot and immunohistochemistry assay were utilized to evaluate the protein level and mRNA level of KIF15 in breast cancer tissues. Then CCK-8, wound healing, transwell and flow cytometry experiments were adopted separately to test cell viability, migration, invasion and cell cycle distribution. We discovered that KIF15 was highly expressed in breast cancer tissues and high level KIF15 was associated with a low survival rate of breast cancer patients. Moreover, silence of KIF15 suppressed cell viability, migration, invasion and cell cycle distribution. Following, we discovered that ZNF367 was the upstream transcription factor of KIF15. In addition, silenced ZNF367 could also repress the growth of breast cancer cells. And rescue experiments indicated that overexpressed KIF15 could counteract the inhibition effect of silencing ZNF367 on the progression of breast cancer. Importantly, we discovered that KIF15 and ZNF367 were associated with the regulation of cell cycle. In short, ZNF367-activated KIF15 accelerated the progression of breast cancer by regulating cell cycle progress.

Machine learning–based diagnostic evaluation of shear-wave elastography in BI-RADS category 4 breast cancer screening: a multicenter, retrospective study Yi Tang, Minjie Liang, Li Tao, Minjun Deng, Tianfu Li