scholarly journals Author Correction: Integrated network analysis identifies hsa-miR-4756-3p as a regulator of FOXM1 in Triple Negative Breast Cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanliang Gu ◽  
Wenjuan Wang ◽  
Xuyao Wang ◽  
Hongyi Xie ◽  
Xiaojuan Ye ◽  
...  
2012 ◽  
Author(s):  
Milan Radovich ◽  
Susan E. Clare ◽  
George W. Sledge ◽  
Ivanesa Pardo ◽  
Theresa Mathieson ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuanliang Gu ◽  
Wenjuan Wang ◽  
Xuyao Wang ◽  
Hongyi Xie ◽  
Xiaojuan Ye ◽  
...  

Abstract Both aberrantly expressed mRNAs and micro(mi)RNAs play important roles in cancer cell function, which makes integration analysis difficult. In this study, we first applied master regulator analysisalgorithm and confirmed hsa-miR-4756-3p as a candidate miRNA in triple negative breast cancer (TNBC) patients; hsa-miR-4756-3p could regulate TNBC cell line apoptosis, proliferation, migration, and cell cycle as well as suppress TGF-β1 signalling andtumour growth. In TNBC, forkhead box protein M1 (FOXM1)was found to be an hsa-miR-4756-3p target gene, and FOXM1 knockout completely inhibited hsa-miR-4756-3p-induced cell migration and metastasis, TGF-β1 signalling, and epithelial mesenchymal signal activation, which indicated that hsa-miR-4756-3p functions via the FOXM1-TGFβ1-EMT axis.


2019 ◽  
Vol 120 (10) ◽  
pp. 16900-16912 ◽  
Author(s):  
Jian Chen ◽  
Xiaojun Qian ◽  
Yifu He ◽  
Xinghua Han ◽  
Yueyin Pan

2020 ◽  
Vol 16 ◽  
pp. 117693432095486
Author(s):  
Wenting Xie ◽  
Zhongshi Du ◽  
Yijie Chen ◽  
Naxiang Liu ◽  
Zhaoming Zhong ◽  
...  

Triple-negative breast cancer (TNBC) is the most aggressive and fatal sub-type of breast cancer. This study aimed to identify metastasis-associated genes that could serve as biomarkers for TNBC diagnosis and prognosis. RNA-seq data and clinical information on TNBC from the Cancer Genome Atlas were used to conduct analyses. Expression data were used to establish co-expression modules using average linkage hierarchical clustering. We used weighted gene co-expression network analysis to explore the associations between gene sets and clinical features and to identify metastasis-associated candidate biomarkers. The K-M plotter website was used to explore the association between the expression of candidate biomarkers and patient survival. In addition, receiver operating characteristic curve analysis was used to illustrate the diagnostic performance of candidate genes. The pale turquoise module was significantly associated with the occurrence of metastasis. In this module, 64 genes were identified, and its functional enrichment analysis revealed that they were mainly associated with transcriptional misregulation in cancer, microRNAs in cancer, and negative regulation of angiogenesis. Further, 4 genes, IGSF10, RUNX1T1, XIST, and TSHZ2, which were negatively associated with relapse-free survival and have seldom been reported before in TNBC, were selected. In addition, the mRNA expression levels of the 4 candidate genes were significantly lower in TNBC tumor tissues compared with healthy tissues. Based on the K-M plotter, these 4 genes were correlated with poor prognosis of TNBC. The area under the curve of IGSF10, RUNX1T1, TSHZ2, and XIST was 0.918, 0.957, 0.977, and 0.749. These findings provide new insight into TNBC metastasis. IGSF10, RUNX1T1, TSHZ2, and XIST could be used as candidate biomarkers for the diagnosis and prognosis of TNBC metastasis.


2021 ◽  
Author(s):  
Jodi M Saunus ◽  
Xavier M De Luca ◽  
Korinne Northwood ◽  
Ashwini Raghavendra ◽  
Alexander Hasson ◽  
...  

Background: Intratumoural heterogeneity is a poor prognostic feature in triple-negative breast cancer (TNBC) and other high-grade malignancies. It is caused by genomic instability and phenotypic plasticity, but how these features co-evolve during tumour development remains unclear. SOX10 is a transcription factor, neural crest stem cell (NCSC) specifier and candidate mediator of cancer-associated phenotypic plasticity. Methods: Using immunophenotyping, we investigated the expression of SOX10 in normal human breast tissue and breast cancer (n=21 cosmetic breast reduction and 1,860 tumour samples with clinical annotation). We then defined the context and evolution of its expression in TNBC compared to 21 other malignancies using systems-level transcriptomics. Results: SOX10 was detected in nuclei of normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In breast cancer, nuclear SOX10 predicted poor outcome amongst cross-sectional (log-rank p=0.0015, hazard ratio 2.02, n=224) and metaplastic (log-rank p=0.04, n=66) TNBCs. Systems-level transcriptional network analysis identified a core module in SOX10′s normal mammary epithelial transcription program that is rewired to NCSC genes in TNBC. Reprogramming was proportional to DNA damage and genome-wide promoter hypomethylation, particularly at CpG island shores. Using a novel network analysis pipeline, we found that NCSC-like transcriptional reprogramming is also strongly associated with promoter hypomethylation in other SOX10+ malignancies: glioma and melanoma. Conclusions: We propose that cancer-associated genome hypomethylation simulates the open chromatin landscape of more primitive cell states, and that on this relatively unrestricted background, SOX10 recreates its ancestral gene regulatory circuits by default. These findings provide new insights about the basis of intratumoural heterogeneity and resurrection of developmental phenotypes in cancer; and highlight the potential for therapeutics that limit chromatin remodelling.


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