Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triple negative breast cancer (TNBC) is aggressive in nature, resistant to conventional therapy and often ends in organ specific metastasis. In this study, publicly available datasets were used to identify miRNA, mRNA and lncRNA hubs. Using validated mRNA-miRNA, mRNA-mRNA and lncRNA-miRNA interaction information obtained from various databases, RNA interaction networks for TNBC and its subtype specific as well as organ tropism regulated metastasis were generated. Further, miRNA-mRNA-lncRNA triad classification was performed using social network analysis from subnetworks and visualized using Cytoscape. Survival analysis of the RNA hubs, oncoprint analysis for mRNAs and pathway analysis of the lncRNAs were also performed. Results indicated that two lncRNAs (NEAT1 and CASC7) and four miRNAs (hsa-miR-106b-5p, hsa-miR-148a-3p, hsa-miR-25-3p and hsa-let-7i-5p) were common between hubs identified in TNBC and TNBC associated metastasis. The exclusive hubs for TNBC associated metastasis were hsa-miR-200b-3p, SP1, HSPA4 and RAB1B. HMGA1 was the top ranked hub in mesenchymal subtype associated lung metastasis, while hsa-miR-27a-3p was identified as the top ranked hub mRNA in luminal androgen receptor subtype associated bone metastasis. When lncRNA associated pathway analysis was performed, Hs Cytoplasmic Ribosomal Protein pathway was found to be the most significant and among the selected hubs, CTNND1, SON and hsa-miR-29c emerged as TNBC survival markers. TP53, FOXA1, MTDH and HDGF were found as the top ranked mRNAs in oncoprint analysis. The pipeline proposed for the first time in this study with validated RNA interaction data integration and graph-based learning for miRNA-mRNA-lncRNA triad classification from RNA hubs may aid experimental cost reduction and its successful execution will allow it to be extended to other diseases too.
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PMID:Identification of mRNA and non-coding RNA hubs using network analysis in organ tropism regulated triple negative breast cancer metastasis. 3312 29

Staphylococcal nuclease domain-containing protein 1 (SND1) is a multifunctional oncoprotein overexpressed in breast cancer. Binding of metadherin (MTDH) to SND1 results in the stabilization of SND1 and is important in the initiation and progression of breast cancer. Disruption of such interaction is a potential therapeutic for breast cancer. SN1/2 domain of SND1 was used as bait in a phage display screening to identify a 12-amino acid peptide 4-2. The activity of peptide 4-2 was evaluated by ELISA, coimmunoprecipitation, MTS, Western blot analysis, and xenograft mouse model. Peptide 4-2 could disrupt SND1-MTDH interaction. Cell penetrating derivative of peptide 4-2 (CPP-4-2) could penetrate and kill breast cancer cells by disrupting SND1-MTDH interaction and degrading SND1. Tryptophan 10 (W10) of peptide 4-2 was essential in mediating cytotoxicity, SND1 interaction, SND1-MTDH disruption, and SND1 degradation. CPP-4-2 could inhibit the growth of breast cancer in a xenograft mouse model. The SND1-interacting peptide 4-2 could kill breast cancer cells both in vitro and in vivo by interacting with SND1, disrupting SND1-MTDH interaction, and inducing SND1 degradation. W10 was an essential amino acid in the activity of peptide 4-2.
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PMID:Disruption of SND1-MTDH Interaction by a High Affinity Peptide Results in SND1 Degradation and Cytotoxicity to Breast Cancer Cells In Vitro and In Vivo. 3326 70


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