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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Identification of mRNA and non-coding RNA hubs using network analysis in organ tropism regulated triple negative
Satarupa Banerjee1, Surya Radhika Kalyani Yabalooru2, Devarajan Karunagaran2
1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, Tamilnadu, India; School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632 014, Tamil Nadu, India.
Abstract:
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.
Insights
This study identifies key RNA hubs (lncRNAs, miRNAs, mRNAs) in aggressive triple-negative breast cancer (TNBC) and its metastasis. The findings offer potential new biomarkers and therapeutic targets for TNBC, improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype resistant to standard therapies.
- TNBC is characterized by high rates of metastasis to various organs.
- Identifying key regulatory molecules is crucial for developing targeted treatments.
Purpose of the Study:
- To identify crucial microRNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) hubs in TNBC.
- To construct and analyze RNA interaction networks for TNBC and its metastasis.
- To classify miRNA-mRNA-lncRNA triads for potential therapeutic targets.
Main Methods:
- Utilized publicly available datasets for TNBC.
- Generated RNA interaction networks using validated interaction data.
- Employed social network analysis and Cytoscape for triad classification.
- Performed survival, oncoprint, and pathway analyses.
Main Results:
- Identified common and exclusive RNA hubs for TNBC and its metastasis.
- Highlighted specific lncRNAs (NEAT1, CASC7) and miRNAs (hsa-miR-106b-5p, hsa-miR-148a-3p, hsa-miR-25-3p, hsa-let-7i-5p) as key players.
- Discovered subtype-specific hubs (e.g., HMGA1, hsa-miR-27a-3p) for lung and bone metastasis.
- CTNND1, SON, and hsa-miR-29c emerged as significant TNBC survival markers.
Conclusions:
- The study proposes a novel pipeline for identifying and classifying RNA interaction triads in TNBC.
- Identified potential biomarkers (NEAT1, CASC7, specific miRNAs, CTNND1, SON) for TNBC and metastasis.
- The integrated approach may reduce experimental costs and can be extended to other cancers.
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