scholarly journals LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

2020 ◽  
Vol 21 (19) ◽  
pp. 7407
Author(s):  
Martin C. Abba ◽  
Romina Canzoneri ◽  
Agustina Gurruchaga ◽  
Jaeho Lee ◽  
Pradeep Tatineni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Breast Cancer Progression ◽  
Early Stage Breast Cancer ◽  
Protein Coding ◽  
Breast Cells ◽  
Invasive Breast Carcinomas

Long intergenic non-protein coding RNA 885 (LINC00885) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by LINC00885 in non-invasive and invasive breast cancer models. We determined that LINC00885 induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by LINC00885, which include bioprocesses related to TP53 signaling pathway and proliferative signatures such as activation of EREG, EGFR and FOXM1 pathways. LINC00885 silencing in breast cancer lines overexpressing this lncRNA leads to downregulation of proliferation related transcripts such as EREG, CMYC, CCND1 and to significant decrease in cell migration and motility. TCGA-BRCA data analyses show an association between high LINC00885 expression and worse overall survival in patients with primary invasive breast carcinomas (p = 0.024), suggesting that the pro-tumorigenic effects of LINC00885 overexpression persist post-invasion. We conclude that LINC00885 behaves as a positive regulator of cell growth both in normal and DCIS breast cells possibly operating as a ceRNA and representing a novel oncogenic lncRNA associated with early stage breast cancer progression.

scholarly journals HOTAIR Modulated Pathways in Early-Stage Breast Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Martin C. Abba ◽  
María Laura Fabre ◽  
Jaeho Lee ◽  
Pradeep Tatineni ◽  
Hyunsuk Kil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Breast Cancer Progression ◽  
Early Stage Breast Cancer ◽  
Cell Growth And Migration ◽  
Mesenchymal Transition ◽  
Over Expression

The long-non-coding HOX transcript antisense intergenic RNA (HOTAIR) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by HOTAIR in early-stage breast cancer progression. We determined that HOTAIR induces premalignant phenotypic changes by increasing cell proliferation, migration, invasion and in vivo growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by HOTAIR which include bioprocesses related to epithelial to mesenchymal transition, cell migration, extracellular matrix remodeling and activation of several signaling pathways (HIF1A, AP1 and FGFR). Similar pathways were identified as activated in primary invasive breast carcinomas with HOTAIR over-expression. We conclude that HOTAIR over-expression behaves as a positive regulator of cell growth and migration both in normal and DCIS breast cells involved with early-stage breast cancer progression.

Abstract 5031: Regulatory T cell ablation accelerates early stage breast cancer progression

2019 ◽  
Author(s):  
Wei Du ◽  
Leandro Martinez ◽  
Valentina Robila ◽  
Nicholas Clark ◽  
Michael Idowu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Cancer Progression ◽  
Regulatory T Cell ◽  
Early Stage ◽  
Breast Cancer Progression ◽  
Early Stage Breast Cancer ◽  
Cell Ablation

Abstract 5031: Regulatory T cell ablation accelerates early stage breast cancer progression

2019 ◽  
Author(s):  
Wei Du ◽  
Leandro Martinez ◽  
Valentina Robila ◽  
Nicholas Clark ◽  
Michael Idowu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Cancer Progression ◽  
Regulatory T Cell ◽  
Early Stage ◽  
Breast Cancer Progression ◽  
Early Stage Breast Cancer ◽  
Cell Ablation

scholarly journals ID2 and GJB2 promote early-stage breast cancer progression by regulating cancer stemness

2019 ◽  
Vol 175 (1) ◽  
pp. 77-90 ◽  
Author(s):  
Yin Liu ◽  
Puspa R. Pandey ◽  
Sambad Sharma ◽  
Fei Xing ◽  
Kerui Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Early Stage ◽  
Breast Cancer Progression ◽  
Early Stage Breast Cancer ◽  
Cancer Stemness

scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

scholarly journals MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Daniel Escuin ◽  
Laura López-Vilaró ◽  
Olga Bell ◽  
Josefina Mora ◽  
Antonio Moral ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Signaling Pathways ◽  
Axillary Lymph Node ◽  
Target Genes ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Axillary Lymph ◽  
Illumina Platform ◽  
Down Regulation

Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the SLN status and the outcome of axillary lymph node dissection (ALND) in 60 patients with early breast cancer. We profiled the expression of miRNAs in paired breast tumor samples and SLNs using the NextSeq500 Illumina platform and key findings were validated by qPCR. MultiMiR Bioconductor and Reactome pathways analysis were performed to identify target genes and signaling pathways affected by altered expressed miRNAs. Our results show that nine miRNAs were differentially expressed in tumor tissues (q ≤ 0.05). In tumor samples, a 13.5-fold up-regulation of miR-7641-2 (q &lt; 0.001) and a 2.9-fold down-regulation of miR-1291 (q &lt; 0.001) were associated with tumors with positive SLNs. However, only down-regulation of miR-1291 (q = 0.048) remained significant in paired SLNs samples. Interestingly, a 10.5 up-regulation of miR-1291 in SLNs samples was associated with additional axillary lymph node involvement (q &lt; 0.001). The enrichment analyses showed that canonical and non-canonical WNT pathways and negative regulation of various receptor tyrosine kinases signaling pathways were targets of miR-1291 and supports the role of miR-1291 as a tumor suppressor gene (TSG). Further studies are warranted to investigate the use of miR-1291 as a surrogate biomarker of SLN node metastasis in patients with early-stage breast cancer.

scholarly journals Comprehensive Analysis of lncRNA and miRNA Regulatory Network Reveals Potential Prognostic Non-coding RNA Involved in Breast Cancer Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Gao ◽  
Xun Lu ◽  
Jingjing Ma ◽  
Qian Zhou ◽  
RanRan Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Progression ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Early Stage ◽  
Breast Cancer Progression ◽  
Poor Overall Survival ◽  
Non Coding Rna

Breast cancer is one of the most common malignant tumors in women and is the second leading cause of cancer deaths among women. The tumorigenesis and progression of breast cancer are not well understood. The existing researches have indicated that non-coding RNAs, which mainly include long non-coding RNA (lncRNA) and microRNA (miRNA), have gradually become important regulators of breast cancer. We aimed to screen the differential expression of miRNA and lncRNA in the different breast cancer stages and identify the key non-coding RNA using TCGA data. Based on series test of cluster (STC) analysis, bioinformatics analysis, and negatively correlated relationships, 122 lncRNAs, 67 miRNAs, and 119 mRNAs were selected to construct the regulatory network of lncRNA and miRNA. It was shown that the miR-93/20b/106a/106b family was at the center of the regulatory network. Furthermore, 6 miRNAs, 10 lncRNAs, and 15 mRNAs were significantly associated with the overall survival (OS, log-rank P &lt; 0.05) of patients with breast cancer. Overexpressed miR-93 in MCF-7 breast cancer cells was associated with suppressed expression of multiple lncRNAs, and these downregulated lncRNAs (MESTIT1, LOC100128164, and DNMBP-AS1) were significantly associated with poor overall survival in breast cancer patients. Therefore, the miR-93/20b/106a/106b family at the core of the regulatory network discovered by our analysis above may be extremely important for the regulation of lncRNA expression and the progression of breast cancer. The identified key miRNA and lncRNA will enhance the understanding of molecular mechanisms of breast cancer progression. Targeting these key non-coding RNA may provide new therapeutic strategies for breast cancer treatment and may prevent the progression of breast cancer from an early stage to an advanced stage.

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