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Breast cancer is a highly heterogeneous disease and numerous secreted factors may differentially contribute to a macrophage phenotype whose extensive infiltration is generally regarded as indicative of an unfavorable outcome. How different breast tumor cells and macrophage cells interplay or influence each other on the alternative splicing (AS) level have not been characterized. Here, we exploited one previous study, which investigated the interplay between macrophages and estrogen receptor‑positive (ER+) breast cancer and triple‑negative breast cancer (TNBC) at the transcriptional level, to investigate the tumor‑macrophage crosstalk at the AS level. In the present study, it was demonstrated that biological processes such as DNA damage and DNA repair were significantly affected both in ER+ breast cancer and TNBC by co‑culturing with macrophages, whereas biological pathways altered in macrophages co‑cultured with tumor cells depended on the breast cancer type. Specifically, biological processes altered in macrophages co‑cultured with ER+ breast cancer were enriched in RNA processing and translation‑related pathways whereas biological processes altered in macrophages co‑cultured with TNBC were mainly enriched in protein transport pathways. We also analyzed the sequence features of skip exons among different conditions. In addition, putative splicing factors which were responsible for the altered AS profile in each condition were identified. The findings of the present study revealed significant tumor‑macrophage crosstalk at the AS level which may facilitate the development of new therapeutic strategies for cancer.
Pubmed ID: 31233192 RIS Download
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Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsProbabilistic framework that quantitates the expression level of alternatively spliced genes from RNA-Seq and identifies differentially regulated isoforms or exons across samples.
View all literature mentionsA database of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). Users can analyze protein sequences for Pfam matches, view Pfam family annotation and alignments, see groups of related families, look at the domain organization of a protein sequence, find the domains on a PDB structure, and query Pfam by keywords. There are two components to Pfam: Pfam-A and Pfam-B. Pfam-A entries are high quality, manually curated families that may automatically generate a supplement using the ADDA database. These automatically generated entries are called Pfam-B. Although of lower quality, Pfam-B families can be useful for identifying functionally conserved regions when no Pfam-A entries are found. Pfam also generates higher-level groupings of related families, known as clans (collections of Pfam-A entries which are related by similarity of sequence, structure or profile-HMM).
View all literature mentionsDatabase of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)
View all literature mentionsA next-generation web-based application that aims to provide an integrated solution for both visualization and analysis of deep-sequencing data, along with simple access to public datasets.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)
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