A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays

Chaudhary, Sanjib; Krishna, B. Madhu; Mishra, Sandip K.

doi:10.3892/ol.2017.6329

Cited by 21 publications

(20 citation statements)

References 83 publications

(82 reference statements)

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“…The open source provides huge amounts of data for the researchers to access, which constitutes an invaluable resource for biological research. Combined with the network analyses, plenty of genes have been identified and used as potential biomarkers and therapeutic targets for different tumors, such as the roles of FOXA1/ESR1 pathway in breast cancer, 29 the expression of SRD5A1 and its prognostic role in prostate cancer, 30 and the clinical significance of MALAT1 in pancreatic cancer 31 …”

Section: Discussionmentioning

confidence: 99%

“…27,28 We wondered whether PYCR1 could affect the JAK/ STAT signaling pathway in LUAD. Therefore, two siRNAs were Combined with the network analyses, plenty of genes have been identified and used as potential biomarkers and therapeutic targets for different tumors, such as the roles of FOXA1/ESR1 pathway in breast cancer, 29 the expression of SRD5A1 and its prognostic role in prostate cancer, 30 and the clinical significance of MALAT1 in pancreatic cancer. 31 In our study, based on the results of Oncomine database, we found that PYCR1 was upregulated in LUAD tissues.…”

Section: Pycr1 Knockdown Affected the Jak/stat Signaling Pathway Inmentioning

confidence: 99%

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PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

Gao

Luo

Xie

et al. 2020

Molecular Carcinogenesis

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Lung adenocarcinoma (LUAD), as a form of non‐small cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer worldwide. To date, a few biomarkers have been reported to provide valuable information in guiding LUAD treatment. The aim of our study was to explore the functional role of pyrroline‐5‐carboxylate reductase 1 (PYCR1) in LUAD. Based on Oncomine database, we found that PYCR1 was highly expressed in LUAD tissues. We also confirmed an abnormal increase of PYCR1 expression in LUAD cell lines and patients' tissues. Through Kaplan‐Meier plotter database, we further studied the prognostic values of PYCR1. The outcomes indicated that overexpressed PYCR1 associated with poor prognosis among LUAD patients. To further study the function of PYCR1 in LUAD, cell counting kit‐8, colony‐forming, scratch wound healing, and Transwell assays were conducted. The results suggested that knockdown of PYCR1 curbed cell proliferation, migration, and invasion in LUAD cell lines. Subsequently, we identified 50 top genes positively and negatively correlated with PYCR1 in LUAD, and conducted biological pathway enrichment analysis of these genes. Among those enriched pathways, we selected JAK/STAT signaling pathway for further analysis. The results of Western blot assays revealed that PYCR1 knockdown significantly increased the expression of Bcl‐2 and c‐Myc, and the phosphorylation level of JAK2 and STAT3. Taken together, this study unearthed that PYCR1 knockdown could inhibit tumor growth and affect the JAK/STAT signaling pathway in LUAD. This study may contribute to a better understanding of PYCR1 in LUAD and provide a potential biomarker for cancer prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Pycr1 Knockdown Affected the Jak/stat Signaling Pathway Inmentioning

confidence: 99%

PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

Gao

Luo

Xie

et al. 2020

Molecular Carcinogenesis

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“…ESR1 and CERS6 (see the section above) were co-expressed in the green module, along with C6orf211 (ARMT1, acidic residue methyltransferase 1), CCND1 (cyclin D1), and THSD4 (thrombospondin type 1 domain containing 4). This set of genes has been suggested as markers for a prognostic luminal signature [104] and has more recently been highlighted as the key players in a novel, FOXA1/ESR1-interacting pathway [131], highlighting their association with estrogen receptor status.…”

Section: Luminal Subtypesmentioning

confidence: 99%

Secreted breast tumor interstitial fluid microRNAs and their target genes are associated with triple-negative breast cancer, tumor grade, and immune infiltration

et al. 2020

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Background: Studies on tumor-secreted microRNAs point to a functional role of these in cellular communication and reprogramming of the tumor microenvironment. Uptake of tumor-secreted microRNAs by neighboring cells may result in the silencing of mRNA targets and, in turn, modulation of the transcriptome. Studying miRNAs externalized from tumors could improve cancer patient diagnosis and disease monitoring and help to pinpoint which miRNA-gene interactions are central for tumor properties such as invasiveness and metastasis. Methods: Using a bioinformatics approach, we analyzed the profiles of secreted tumor and normal interstitial fluid (IF) microRNAs, from women with breast cancer (BC). We carried out differential abundance analysis (DAA), to obtain miRNAs, which were enriched or depleted in IFs, from patients with different clinical traits. Subsequently, miRNA family enrichment analysis was performed to assess whether any families were over-represented in the specific sets. We identified dysregulated genes in tumor tissues from the same cohort of patients and constructed weighted gene co-expression networks, to extract sets of co-expressed genes and co-abundant miRNAs. Lastly, we integrated miRNAs and mRNAs to obtain interaction networks and supported our findings using prediction tools and cancer gene databases.

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“…An entry manifests combination c if all the genes in this combination are above their respective median expression level. Since this sample is Luminal B, it is expected that ESR1, FOXA1 and GATA3 would be spatially co-expressed [31, 65, 12], leading to a significantly homogeneous HTA index. We tested both two and three traits.…”

Section: Resultsmentioning

confidence: 99%

Assessing heterogeneity in spatial data using the HTA index with applications to spatial transcriptomics and imaging

Levy-Jurgenson

Tekpli

Yakhini

2021

Preprint

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Tumour heterogeneity is being increasingly recognised as an important characteristic of cancer and as a determinant of prognosis and treatment outcome. Emerging spatial transcriptomics data hold the potential to further our understanding of tumour heterogeneity and its implications. However, existing statistical tools are not sufficiently powerful to capture heterogeneity in the complex setting of spatial molecular biology. We provide a statistical solution, the HeTerogeneity Average index (HTA), specifically designed to handle the multivariate nature of spatial transcriptomics. We prove that HTA has an approximately normal distribution, therefore lending itself to efficient statistical assessment and inference. We first demonstrate that HTA accurately reflects the level of heterogeneity in simulated data. We then use HTA to analyse heterogeneity in two cancer spatial transcriptomics datasets: spatial RNA sequencing by 10x Genomics and spatial transcriptomics inferred from H&E. Finally, we demonstrate that HTA also applies to 3D spatial data using brain MRI. In spatial RNA sequencing we use a known combination of molecular traits to assert that HTA aligns with the expected outcome for this combination. We also show that HTA captures immune-cell infiltration at multiple resolutions. In digital pathology we show how HTA can be used in survival analysis and demonstrate that high levels of heterogeneity may be linked to poor survival. In brain MRI we show that HTA differentiates between normal ageing, Alzheimer's disease and two tumours. HTA also extends beyond molecular biology and medical imaging, and can be applied to many domains, including GIS. Source code and python package are available at https://alonalj.github.io/HTA.html .

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A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays

Cited by 21 publications

References 83 publications

PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

Secreted breast tumor interstitial fluid microRNAs and their target genes are associated with triple-negative breast cancer, tumor grade, and immune infiltration

Assessing heterogeneity in spatial data using the HTA index with applications to spatial transcriptomics and imaging

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