Identification of cuproptosis-related miRNAs in triple-negative breast cancer and analysis of the miRNA-mRNA regulatory network.

Introduction: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. Purpose: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. Methods: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort. Conducting differential analysis resulted in the identification of differentially expressed miRNA (DE-miRNAs) and differentially expressed genes (DEGs) between the TNBC and Control samples. Screening for prognostic miRNAs and biomarkers involved employing univariate Cox analysis and least absolute shrinkage and selection operator regression analyses. These methods were utilized to construct risk models aimed at predicting the survival of patients with TNBC. Based on the median value of risk scores, patients were then stratified into low- and high-risk groups. Functional enrichment analysis was employed to explore the potential function and pathways of prognostic genes. Additionally, independent prognostic analysis was performed through univariate and multivariate Cox regression. Immune infiltration analysis was performed to examine disparities in the infiltration of immune cells between the two risk groups. Finally, the prognostic gene expression was mined in key cell types of TNBC. Results: We obtained 5213 DEGs and 204 DE-miRNAs related to cuproptosis between TNBC and Control samples. Five prognostic miRNAs (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were closely associated with TNBC. Significant differences in the functions of prognostic genes between the two risk groups were observed, encompassing adipogenesis, inflammatory response, and hormone metabolic process. The prognostic gene regulatory network revealed that miR200C-3p regulated ZFPM2 and CFL2, and miR-1277-3p regulated BMP2 and RORA. A nomogram was created based on riskScore, cancer status, and pathologic stage to predict 1/3/5-year survival of patients with TNBC. Immune infiltration analysis indicated that the immune microenvironment may be associated with the progression of TNBC. Interestingly, prognostic genes exhibited higher expression levels in T cells, fibroblasts, endothelial cells, and monocytes compared to other cells. Conclusions: Five prognostic miRNA (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were significantly associated with TNBC, it provides new therapeutic targets for the treatment and prognosis of TNBC.

Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR-326/FGFR1 axis.

BACKGROUND: Breast cancer (BC) is a heterogeneous malignant tumor that threatens the health of women worldwide. Hsa_circRNA_0000518 (circ_0000518) has been revealed to be upregulated in BC tissues. However, the role and mechanism of circ_0000518 in BC are indistinct. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to detect the levels of circ_0000518, microRNA (miR)-326, and fibroblast growth factor receptor 1 (FGFR1) mRNA in BC tissues and cells. Cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays were executed to estimate BC cell proliferation, cell cycle progression, apoptosis, migration, and invasion. The relationship between circ_0000518 or FGFR1 and miR-326 was verified by dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. The role of circ_0000518 in vivo was confirmed by xenograft assay. RESULTS: Circ_0000518 and FGFR1 were upregulated while miR-326 was downregulated in BC tissues and cells. Circ_0000518 silencing impeded tumor growth in vivo and induced cell cycle arrest, apoptosis, cured proliferation, colony formation, migration, and invasion of BC cells in vitro. Circ_0000518 regulated FGFR1 expression via competitively binding to miR-326 in BC cells. MiR-326 inhibitor reversed the inhibitory influence of circ_0000518 knockdown on the malignant behaviors of BC cells. FGFR1 overexpression abolished miR-326 mimic-mediated influence on the malignant behaviors of BC cells. CONCLUSIONS: Circ_0000518 facilitated BC development via regulation of the miR-326/FGFR1 axis, suggesting that circ_0000518 might be a promising target for BC treatment.

Dynamic Regulative Biomarker: Long Noncoding RNA (lncRNA) in Metastatic Breast Cancer.

BACKGROUND: Breast tumor is a common cancer in women all over the world. Long noncoding RNA (lncRNA) provides a significant and new perspective on understanding biomarkers as well as on the potential prognostic regulation of breast cancer. Its transcription, in turn, serves as a regulator in diagnosing breast cancer and preventing risk of recurrence. Here, we review the evolution of lncRNAs and discuss their regulative roles in the metastasis of breast cancer. Moreover, we aim to detect the expression level of lncRNA HOTAIR in different stages of breast cancer. METHODS: Sixty patients with breast cancer at different stages were divided into four groups based on different stages. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of lncRNA HOTAIR in breast tumor tissue. RESULTS: Compared to stage I breast cancer, the expression profiles of lncRNA HOTAIR in stage II, III, IV breast cancer are significantly elevated (p < 0.05). The expression profiles of lncRNA HOTAIR in stage III and IV breast cancer are significantly increased compared with stage II breast cancer. CONCLUSIONS: Consistent with microRNAs (miRNA), lncRNAs could function as underlying effective biomarkers to affect the biogenesis and gene control across all lifetime. The interaction between lncRNA and miRNA plays a crucial role in the metastasis of breast cancer and provides a potential biomarker target for breast cancer metastasis therapy. Our study has also demonstrated that the expression profiles of lncRNA HOTAIR in stage II, III, IV breast cancer are significantly elevated.

A Novel lncRNA HOXC-AS3 Acts as a miR-3922-5p Sponge to Promote Breast Cancer Metastasis.

Purpose: The function of long noncoding RNAs (lncRNA) in breast cancer metastasis remains largely unknown. In this work, the role of HOXC-AS3 in breast cancer progression was investigated.Methods: By using Cancer Genome Atlas (TCGA) Database, we investigated the expression of HOXC-AS3 in breast cancer and explored the association between HOXC-AS3 expression and prognosis. Then, we studied the biological function of HOXC-AS3 in cell migration and invasion both in vitro and in vivo. Furthermore, the target miRNA of HOXC-AS3, and the target mRNA of miR-3922-5p were proved.Results: HOXC-AS3 is aberrantly overexpressed in breast cancers especially the HER2+ type. Moreover, high expression of HOXC-AS3 has a relationship with poor clinical outcomes of breast cancer. In addition, HOXC-AS3 regulates cell Invasion and migration both in vitro and in vivo. Our results demonstrated that miR-3922-5p was a direct target of HOXC-AS3, and PPP1R1A was a target of miR-3922-5p in breast cancer.Conclusions: The novel lncRNA HOXC-AS3 acts as a miR-3922-5p sponge to upregulate PPP1R1A protein expression, and thus results in promoting breast cancer metastasis. HOXC-AS3 could be a novel therapeutic target for breast cancer therapeutics.

A Reliable Method: Purse-String Hemostasis for Arteriovenous Fistula or Arteriovenous Graft Cannulation after Percutaneous Transluminal Angioplasty.

Percutaneous transluminal angioplasty (PTA) is the most common therapy used to treat dialysis patients with an occluded arteriovenous fistula (AVF) or arteriovenous graft (AVG). AVF or AVG hemostasis after PTA is time consuming, and it may be complicated with acute thrombosis of the AVF or AVG and re-bleeding from the puncture site. In this study, we prospectively studied 145 hemodialysis patients with occluded AVF or AVG using a modified purse-string suture with short tubing tourniquet technique for hemostasis following PTA, during which we used heparin and urokinase infusion. The results indicated that the modified technique for hemostasis of AVF orAVG was effective and safe in achieving immediate hemostasis withoutmanual compression in all patients.

Long non-coding RNA BRAF-regulated lncRNA 1 promotes lymph node invasion, metastasis and proliferation, and predicts poor prognosis in breast cancer.

Long non-coding RNAs (lncRNAs) are primary regulators of cancer development via their involvement in almost every aspect of cell biology. Recent studies have indicated that lncRNAs serve pivotal roles in breast cancer (BC) progression; however, to the best of our knowledge, the role of the lncRNA BRAF-regulated lncRNA 1 (BANCR) in BC has not yet been elucidated. The present study revealed that BANCR was overexpressed in BC cell lines and tissues, and could promote the clinical progression of disease, including increases in tumor size, lymph node metastasis and Tumor-Node-Metastasis stage. Furthermore, high BANCR expression was demonstrated to be associated with poor overall survival rates and early recurrence of BC in patients. Additionally, univariate and multivariate COX regression analyses identified high BANCR expression as an independent risk factor of poor prognosis of patients with BC. In addition, to verify the function of BANCR in BC cell lines, BANCR expression was silenced using short hairpin RNAs in MDA-MB-231 cells and overexpressed in MDA-MB-468 cells. An MTT assay and colony formation assay indicated that BANCR knockdown could suppress the proliferation of BC cells, whereas BANCR upregulation induced the proliferation of BC cells. Furthermore, BANCR silencing also reduced the migration and invasion of BC cells, as demonstrated via transwell migration and invasion assays. Consistently, the migration and invasion of BC cells increased upon BANCR ectopic overexpression in MDA-MB-468 cells. Mechanistically, matrix metallopeptidase 2/9 and epithelial-mesenchymal transition markers may be the potential targets of BANCR in regulating BC metastasis. In conclusion, BANCR overexpression could promote the clinical progression, metastasis and proliferation of BC and indicate poor prognosis of patients with BC. BANCR may therefore be a potential prognostic marker and therapeutic target of patients with BC.

Identification of altered pathways in breast cancer based on individualized pathway aberrance score.

The objective of the present study was to identify altered pathways in breast cancer based on the individualized pathway aberrance score (iPAS) method combined with the normal reference (nRef). There were 4 steps to identify altered pathways using the iPAS method: Data preprocessing conducted by the robust multi-array average (RMA) algorithm; gene-level statistics based on average Z; pathway-level statistics according to iPAS; and a significance test dependent on 1 sample Wilcoxon test. The altered pathways were validated by calculating the changed percentage of each pathway in tumor samples and comparing them with pathways from differentially expressed genes (DEGs). A total of 688 altered pathways with P<0.01 were identified, including kinesin (KIF)- and polo-like kinase (PLK)-mediated events. When the percentage of change reached 50%, 310 pathways were involved in the total 688 altered pathways, which may validate the present results. In addition, there were 324 DEGs and 155 common genes between DEGs and pathway genes. DEGs and common genes were enriched in the same 9 significant terms, which also were members of altered pathways. The iPAS method was suitable for identifying altered pathways in breast cancer. Altered pathways (such as KIF and PLK mediated events) were important for understanding breast cancer mechanisms and for the future application of customized therapeutic decisions.

LncRNA MEG3 inhibits cell epithelial-mesenchymal transition by sponging miR-421 targeting E-cadherin in breast cancer.

BACKGROUND: MEG3, a lncRNA, has been verified in several tumors to function as tumor suppressors including breast cancer development and progression, however, the expression pattern and underlying mechanisms of MEG3 involved in breast cancer progression is still need to be further explored. METHODS: The expression of MEG3 was confirmed in 90 cases of breast cancer tissues compared to adjacent normal tissues by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The association between clinicopathological factors and MEG3 expression was evaluated by chi-square test. Kaplan-Meier curve and log rank test was performed to assess disease-free survival (DFS) and overall survival (OS) time in patients. CCK8 and transwell invasion assays were used to assess cell proliferation and invasion capacity. Luciferase report assay and RNA pull down assay were used to detect the association between miR-421 and MEG3 in breast cancer. RESULTS: In the study, we demonstrated that the expression of MEG3 was significantly down-regulated in breast cancer tissues compared to adjacent normal tissues. Reducing MEG3 expression was significantly associated with TNM stage and lymph nodes metastasis in patients. Survival analysis showed that lower MEG3 predicted a poor DFS and OS for patients. In vitro, we showed that up-regulated MEG3 inhibited cell proliferation and cell invasion capacities. We further revealed that endogenous miR-421 expression was negatively regulated by MEG3 in breast cancer cells and MEG3 regulated E-cadherin expression by sponging to miR-421 in breast cancer cells. CONCLUSIONS: Our results showed that MEG3/miR-421/E-cadherin regulatory axis may be a novel therapeutic target for breast cancer.