scholarly journals Identification of miRNA Master Regulators in Breast Cancer

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1610 ◽  
Author(s):  
Antonio Daniel Martinez-Gutierrez ◽  
David Cantú de León ◽  
Oliver Millan-Catalan ◽  
Jossimar Coronel-Hernandez ◽  
Alma D. Campos-Parra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Locally Advanced ◽  
Bioinformatic Analysis ◽  
Ras Signaling ◽  
Sequencing Data ◽  
Over Expression ◽  
Cancer Pathways ◽  
Complex Processes ◽  
Cancer Transcriptome

Breast cancer is the neoplasm with the highest number of deaths in women. Although the molecular mechanisms associated with the development of this tumor have been widely described, metastatic disease has a high mortality rate. In recent years, several studies show that microRNAs or miRNAs regulate complex processes in different biological systems including cancer. In the present work, we describe a group of 61 miRNAs consistently over-expressed in breast cancer (BC) samples that regulate the breast cancer transcriptome. By means of data mining from TCGA, miRNA and mRNA sequencing data corresponding to 1091 BC patients and 110 normal adjacent tissues were downloaded and a miRNA–mRNA network was inferred. Calculations of their oncogenic activity demonstrated that they were involved in the regulation of classical cancer pathways such as cell cycle, PI3K–AKT, DNA repair, and k-Ras signaling. Using univariate and multivariate analysis, we found that five of these miRNAs could be used as biomarkers for the prognosis of overall survival. Furthermore, we confirmed the over-expression of two of them in 56 locally advanced BC samples obtained from the histopathological archive of the National Cancer Institute of Mexico, showing concordance with our previous bioinformatic analysis.

scholarly journals Overexpression of CCNE1 confers a poorer prognostic in triple negative breast cancer identified by bioinformatic analysis

2020 ◽  
Author(s):  
Qianqian Yuan ◽  
Lewei Zheng ◽  
Yiqin Liao ◽  
Gaosong Wu
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Cancer Survival ◽  
Process Analysis ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus

Abstract Background. Triple-negative breast cancer (TNBC) is a major subtype of breast cancer. Due to the lack of effective therapeutic targets, the prognosis is poor. In order to find an effective target, despite many efforts, the molecular mechanisms of TNBC are still not well understood which remain to be a profound clinical challenge.Methods. To identify the candidate genes in the carcinogenesis and progression of TNBC, microarray datasets GSE36693 and GSE65216 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and functional and pathway enrichment analyses were performed using the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) databases via DAVID. We constructed the protein-protein interaction network (PPI) and the performed the module analysis using STRING and Cytoscape. Then we reanalyzed the selected DEGs genes and the survival analysis was performed using cBioportal.Results. A total of 140 DEGs were identified, consisting of 69 upregulated genes and 71 downregulated genes. Three hub genes were up-regulated among the selected genes from PPI and biological process analysis uncovered the fact that these genes were mainly enriched in p53 pathway and the pathways in cancer. Survival analysis showed that only CCNE1 may be involved in the carcinogenesis, invasion or recurrence of TNBC. Conclusion. CCNE1 could confer a poorer prognostic in TNBC identified by bioinformatic analysis and play key roles in the progression of TNBC which may contribute potential targets for the diagnosis, treatment and prognosis assessment of TNBC.

Phase II study of the multikinase inhibitor dovitinib (TKI258) or placebo in combination with fulvestrant in postmenopausal, endocrine resistant HER2-/HR+ breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS1148-TPS1148
Author(s):  
Fabrice Andre ◽  
Richard Greil ◽  
Neelima Denduluri ◽  
Alejandro Javier Yovine ◽  
Cathy Reddick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Phase Ii ◽  
Molecular Mechanisms ◽  
Locally Advanced ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Predictive Biomarkers ◽  
Her2 Breast Cancer ◽  
Patient Reported

TPS1148 Background: Overcoming endocrine resistance is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer. Molecular mechanisms associated with endocrine resistance include adaptive “cross-talk” between the estrogen receptor and the fibroblast growth factor receptor (FGFR). Up to 8% of HR+/HER2- breast cancer patients (pts) have amplification of the FGFR1 gene, which is associated with resistance to endocrine therapy but can be overcome via FGFR1 inhibition in preclinical models. Dovitinib is a potent FGF, VEGF, and PDGF receptor tyrosine kinase inhibitor that demonstrated antitumor activity in heavily pretreated breast cancer pts with FGF pathway amplification (FGFR1, FGFR2, or ligand FGF3; Andre et al, ASCO 2011). Dovitinib may reverse resistance to endocrine therapy related to FGF-pathway amplification and is studied here to determine if it can improve outcomes when combined with fulvestrant. Methods: Postmenopausal HER2-/HR+ locally advanced or metastatic breast cancer pts (N»150) progressing within 12 months of completion of adjuvant endocrine therapy or after ≤ 1 prior endocrine therapy in the advanced setting will be enrolled in this multicenter, randomized, double blind, placebo controlled, phase II trial. Pts will prospectively undergo molecular screening to enrich for FGF-amplification (FGFR1, FGFR2, or FGF3 amplification by qPCR; 45 amplified and 30 non-amplified pts per arm). Pts will be randomized 1:1 to receive fulvestrant (500 mg q4w [with an additional dose 2 wks after the initial dose]) in combination with oral dovitinib (500 mg, 5 days on/2 days off) or placebo until disease progression, unacceptable toxicity, or death. The primary endpoint is progression-free survival, with tumor assessments performed q8w. Secondary endpoints include overall response rate per RECIST v1.1, duration of response, overall survival, ECOG performance status and patient reported outcome scores over time, and safety. The pharmacodynamic effect of dovitinib on FGFR-associated angiogenic pathways in tumor specimens and potential predictive biomarkers of response to dovitinib will be explored.

scholarly journals Overexpression of CCNE1 confers a poorer prognosis in triple-negative breast cancer identified by bioinformatic analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qianqian Yuan ◽  
Lewei Zheng ◽  
Yiqin Liao ◽  
Gaosong Wu
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Cancer Survival ◽  
Process Analysis ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus

Abstract Background Triple-negative breast cancer (TNBC) is a major subtype of breast cancer. Due to the lack of effective therapeutic targets, the prognosis is poor. In order to find an effective target, despite many efforts, the molecular mechanisms of TNBC are still not well understood which remain to be a profound clinical challenge. Methods To identify the candidate genes in the carcinogenesis and progression of TNBC, microarray datasets GSE36693 and GSE65216 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and functional and pathway enrichment analyses were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases via DAVID. We constructed the protein-protein interaction network (PPI) and performed the module analysis using STRING and Cytoscape. Then, we reanalyzed the selected DEG genes, and the survival analysis was performed using cBioportal. Results A total of 140 DEGs were identified, consisting of 69 upregulated genes and 71 downregulated genes. Three hub genes were upregulated among the selected genes from PPI, and biological process analysis uncovered the fact that these genes were mainly enriched in p53 pathway and the pathways in cancer. Survival analysis showed that only CCNE1 may be involved in the carcinogenesis, invasion, or recurrence of TNBC. The expression levels of CCNE1 were significantly higher in TNBC cells than non-TNBC cells that were detected by qRT-PCR (P < 0.05). Conclusion CCNE1 could confer a poorer prognosis in TNBC identified by bioinformatic analysis and plays key roles in the progression of TNBC which may contribute potential targets for the diagnosis, treatment, and prognosis assessment of TNBC.

scholarly journals GABRQ is Overexpressed and Correlated with Tumor Progression in Breast Cancer

2021 ◽  
Author(s):  
Ran Mei ◽  
Xichun Cui ◽  
Lili Zheng ◽  
Li Jingyi
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Bioinformatic Analysis ◽  
Gamma Aminobutyric Acid ◽  
Nude Mouse Model ◽  
Expression Levels ◽  
The Public

Abstract Background: Breast cancer (BRCA) is the most common type of women's cancer with a high incidence. The function of gamma-aminobutyric acid A receptor θ subunit (GABRQ) has been studied in other cancers. The results demonstrated that the expression levels of GABRQ were closely associated with tumor prognosis. However, the functions and mechanisms of GABRQ in BRCA remain unclear.Materials and methods: We used the public genome datasets and a tissue microarray (TMA) cohort to analyze the GABRQ expression levels. We performed Immunohistochemistry (IHC) and Western blot to determine GABRQ expression in BRCA cell lines and tissues. Cell proliferation was assessed by EDU assay and colony formation assay. Transwell assay was carried out to investigate the cell invasion ability in vitro and Xenograft nude mouse model was constructed to test the function of GABRQ on tumor growth in vivo. Moreover, we utilized bioinformatic analysis to identify the potential molecular mechanisms mediated by GABRQ modification in BRCA.Results: GABRQ was markedly up-regulated in BRCA tissues, and the expression levels of GABRQ were closely associated with BRCA prognosis. Functional analysis elucidated that knockdown of GABRQ could suppress BRCA cell growth and invasion in vitro, and inhibit tumor development in vivo. Moreover, we found that GABRQ overexpression activated the EMT signaling pathway.Conclusions: These results demonstrated that the function of GABRQ in BRCA progression provided potential prognostic predictors for BRCA patients.

scholarly journals Frequency and clinical characteristics of HER2 over-expressed breast cancer in Saudi Arabia: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jamal Zekri ◽  
Ahmed Saadeddin ◽  
Hulayel Alharbi
Keyword(s):  
Breast Cancer ◽  
Saudi Arabia ◽  
Survival Data ◽  
Hormone Receptor ◽  
Clinical Characteristics ◽  
Locally Advanced ◽  
Age At Diagnosis ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Over Expression

Abstract Introduction This study aimed to determine the frequency of human epidermal growth factor receptor 2 (HER2) over-expression in newly diagnosed breast cancer (BC) patients in Saudi Arabia and to assess the clinical characteristics and outcomes in patients with HER2-positive disease. Methods In the first part of the study, we retrospectively reviewed the pathology records of all patients diagnosed with BC between 2007 and 2013 at 3 hospitals in the largest 3 cities in Saudi Arabia to determine the frequency of HER2 over-expression. In the second part, a representative sample from the patients identified with HER2 over-expressed BC was selected for further investigation. Data collected included demographic and clinical characteristics such as hormone-receptor status, treatment regimens, survival data, response to treatment, and selected adverse events. Results 1867 BC records were included in the study. HER2 was overexpressed in 559 patients (29.9%); of those, 348 HER2-positive BC patients were included in subsequent analyses. In the sample of HER2-positive BC patients, median age at diagnosis was 46 years, 0.9% were male, 92.5% were Saudi, 42.4% were Hormone Receptor-negative, and 13.1% had stage IV tumors. Most patients (84.2%) underwent curative intent surgery and 71.8% received radiotherapy. Average tumor size was 3.5 ± 2.5 cm and infiltrating ductal carcinoma was the most common pathology (92.9%). As for pharmacological therapy, the most commonly used regimens were Chemotherapy + Trastuzumab combination (79.1%) in neoadjuvant setting, Hormonotherapy alone (56.2%) in adjuvant setting, and Chemotherapy + Targeted therapy combination (64.8%) as palliative treatment. At the last patient evaluation, 36.9% had complete response, while 33.2% had progressive disease. Median overall survival (OS) and progression-free survival (PFS) were not reached in patients on neoadjuvant/adjuvant pharmacotherapy. As for patients on palliative intent pharmacotherapy, median OS and PFS were 64.7 and 29.3 months respectively. Conclusion This study provided updated figures regarding HER2 overexpression in BC in Saudi Arabia: HER2 overexpression rate (29.9%) was within the range reported in previous studies. Patients’ demographic and clinical characteristics were also similar to those reported earlier, with a median age at diagnosis of 46 years and one third of patients having locally advanced/metastatic disease at diagnosis.

scholarly journals The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer

2019 ◽  
Author(s):  
Deepak Poduval ◽  
Zuzana Sichmanova ◽  
Anne Hege Straume ◽  
Per Eystein Lønning ◽  
Stian Knappskog
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Locally Advanced Breast Cancer ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Transcriptional Level ◽  
Sequencing Data ◽  
Expression Array ◽  
Expression Levels

AbstractmiRNAs are an important class of small non-coding RNAs, which play a versatile role in gene regulation at the post-transcriptional level. Expression of miRNAs is often deregulated in human cancers.We analyzed small RNA massive parallel sequencing data from 50 locally advanced breast cancers aiming to identify novel breast cancer related miRNAs. We successfully predicted 10 novel miRNAs, out of which 2 (hsa-miR-nov3 and hsa-miR-nov7) were recurrent. Applying high sensitivity qPCR, we detected these two microRNAs in 206 and 214 out of 223 patients in the study from which the initial cohort of 50 samples were drawn. We found hsa-miR-nov3 and hsa-miR-nov7 both to be overexpressed in tumor versus normal breast tissue in a separate set of 13 patients (p=0.009 and p=0.016, respectively) from whom both tumor tissue and normal tissue were available. We observed hsa-miR-nov3 to be expressed at higher levels in ER-positive compared to ER-negative tumors (p=0.037). Further stratifications revealed particularly low levels in the her2-like and basal-like cancers compared to other subtypes (p=0.009 and 0.040, respectively).We predicted target genes for the 2 microRNAs and identified inversely correlated genes in mRNA expression array data available from 203 out of the 223 patients. Applying the KEGG and GO annotations to target genes revealed pathways essential to cell development, communication and homeostasis.Although a weak association between high expression levels of hsa-miR-nov7 and poor survival was observed, this did not reach statistical significance. hsa-miR-nov3 expression levels had no impact on patient survival.

scholarly journals Overexpression of CCNE1 confers a poorer prognostic in triple negative breast cancer identified by bioinformatic analysis

2021 ◽  
Author(s):  
Qianqian Yuan ◽  
Lewei Zheng ◽  
Yiqin Liao ◽  
Gaosong Wu
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Cancer Survival ◽  
Process Analysis ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus

Abstract Background. Triple-negative breast cancer (TNBC) is a major subtype of breast cancer. Due to the lack of effective therapeutic targets, the prognosis is poor. In order to find an effective target, despite many efforts, the molecular mechanisms of TNBC are still not well understood which remain to be a profound clinical challenge.Methods. To identify the candidate genes in the carcinogenesis and progression of TNBC, microarray datasets GSE36693 and GSE65216 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and functional and pathway enrichment analyses were performed using the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) databases via DAVID. We constructed the protein-protein interaction network (PPI) and the performed the module analysis using STRING and Cytoscape. Then we reanalyzed the selected DEGs genes and the survival analysis was performed using cBioportal.Results. A total of 140 DEGs were identified, consisting of 69 upregulated genes and 71 downregulated genes. Three hub genes were up-regulated among the selected genes from PPI and biological process analysis uncovered the fact that these genes were mainly enriched in p53 pathway and the pathways in cancer. Survival analysis showed that only CCNE1 may be involved in the carcinogenesis, invasion or recurrence of TNBC. Conclusion. CCNE1 could confer a poorer prognostic in TNBC identified by bioinformatic analysis and play key roles in the progression of TNBC which may contribute potential targets for the diagnosis, treatment and prognosis assessment of TNBC.

scholarly journals Proteomic Analysis of MCF-7 Breast Cancer Cell Line Exposed To Leptin

2011 ◽  
Vol 34 (3) ◽  
pp. 147-157 ◽  
Author(s):  
A. Valle ◽  
J. Sastre-Serra ◽  
C. Pol ◽  
A. M. Miró ◽  
J. Oliver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Cancer Cell Line ◽  
Ubiquitin Proteasome System ◽  
Tumor Formation ◽  
Ras Signaling ◽  
Two Dimensional Gel Electrophoresis ◽  
Flight Mass Spectrometry ◽  
As Stress ◽  
Mcf 7

Background: Obesity is a well-known factor risk for breast cancer in postmenopausal women. Circulating leptin levels are increased in obese and it has been suggested to play an important role in mammary tumor formation and progression. To contribute to the understanding of the molecular mechanisms underlying leptin action in breast cancer, our aim was to identify proteins regulated by leptin in MCF-7 human breast cancer cells.Methods: We used two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) to identify proteins affected by leptin.Results: Thirty proteins were found differentially expressed in MCF-7 cells after 48 h leptin exposure. Proteins regulated by leptin included proteins previously implicated in breast cancer such as catechol-o-methyltransferase, cathepsin D, hsp27, serine/threonine-protein phosphatase and regulatory proteins of the Ras signaling pathway. Proteins involved in other cellular functions such as stress response, cytosqueleton remodeling and proteins belonging to ubiquitin-proteasome system, were also identified. Furthermore, leptin-treated cells showed a substantial uptake of the serum carrier proteins albumin and alpha-2-HS-glycoprotein.Conclusions: This screening reveals that leptin influences the levels of key proteins involved in breast cancer which opens new avenues for the study of the molecular mechanisms linking obesity to breast cancer.

scholarly journals Corylin sensitizes breast cancer cells to overcome tamoxifen resistance by regulating OAS1/miR-22-3p/SIRT1 axis

2021 ◽  
Author(s):  
Li Che ◽  
Hongru Yang ◽  
Daijie Wang ◽  
Shourong Liu
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Tamoxifen Resistance ◽  
Bioinformatic Analysis ◽  
Mrna Targets ◽  
Direct Target ◽  
Resistant Cells

Breast cancer (BCa) is one of the leading causes of cancer-related death among women worldwide. At present, the clinical treatment with tamoxifen (TAM) is challenged by the development of drug resistance. To investigate the effect of corylin on TAM resistance in BCa cells, this study investigated the molecular mechanisms involving miRNA-mRNA targets modulated by corylin. The TAM-resistant MCF-7TR and T47DTR cell lines were generated, and it was found that corylin treatment reduced the cell viability of these cells significantly. Furthermore, OAS1 was validated to be highly expressed in TAM-resistant cells, while OAS1 knockdown sensitized MCF-7TR and T47DTR cells to TAM treatment. Meanwhile, OAS1 was also repressed by corylin treatment, indicating that OAS1 was a key regulator of corylin function. Through bioinformatic analysis, the tumor suppressive miRNA miR-22-3p was identified to directly target and inhibit OAS1. Moreover, corylin treatment up-regulated miR-22-3p expression, which thus down-regulated the OAS1 expression. Interestingly, OAS1 itself functioned as a miR-22-3p sponge to repress miR-22-3p expression. Further, SIRT1 was identified to be up-regulated in TAM-resistant cells and participated in the OAS1/miR-22-3p regulatory axis via the miR-22-3p direct target. In conclusion, corylin sensitized TAM-resistant cells to TAM treatment by inhibiting OAS1 expression and modulating the OAS1/miR-22-3p/SIRT1 axis.

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