Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer
Abstract
:1. Introduction
2. Results
2.1. Expression Datasets and Gene Annotations
2.2. Module Detection of Interconnected Genes
2.3. The Correlation of Modules with the Sample Phenotype
2.4. Module Preservation in Independent Datasets
2.5. The Potential Interactions of RKIP/PEBP1 with Autophagy and EMT Gene Products
2.6. Common Regulators of RKIP/PEBP1 and Its Interacting Partners
2.7. Validation of Selected Gene Product Correlations with RKIP/PEBP1
3. Discussion
4. Materials and Methods
4.1. Data and Annotation Sources
4.2. Weighted-Gene Co-Expression Network Analysis
4.3. Protein–Protein Interactions
4.4. Transcription Regulators Analysis
4.5. Cell Culture and Immunocytochemistry
4.6. Co-Localization Image Analysis
4.7. Software Environment and Reproducibility
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
RKIP | Raf Kinase Inhibitor Protein |
PEBP1 | Phosphatidylethanolamine Binding Protein 1 |
PEB | Phosphatidylethanolamine Binding |
EMT | Epithelial to Mesenchymal Transition |
WGCNA | Weighted-Gene Co-expression Network Analysis |
GO | Gene Ontology |
TOM | Topological Overlap Matrix |
PC | Principal Component |
ROI | Region of Interest |
RNA-Seq | RNA Sequencing |
ChIP-Seq | Chromatin Immunopreciptation followed by DNA Sequencing |
NCI | National Cancer Institute |
Appendix A. A Note on Reproducing the Analysis
Appendix A.1. Setting up the Docker Environment
- $ docker pull bcmslab/rkip
- $ docker run -it bcmslab/rkip bash
Appendix A.2. Obtaining the Source Code
- ’get_data.R’ This script downloads several datasets from different sources in preparation of the analysis
- ’analysis.R’ This script loads the required libraries, downloads the data and runs all the steps of the analysis described in the manuscript
- ’figures/’ A sub-folder with a separate file for each graph in the manuscript.
- ’tables/’ A sub-folder with a separate file for each table in the manuscript.
- $ git clone https://github.com/BCMSLab/rkip
Appendix A.3. Running the Analysis
- $ cd rkip/analysis/
- $ make
Appendix A.4. Details of the R Environment
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Study ID | Samples | Genes | Reference |
---|---|---|---|
prad.broad.2013 | 7 | 150 | [8] |
prad.broad | 20 | 143 | [9] |
prad.fhcrc | 171 | 149 | [10] |
prad.mskcc.cheny1.organoids.2014 | 10 | 148 | [11] |
prad.mskcc | 150 | 151 | [12] |
prad.su2c.2015 | 118 | 152 | [13] |
prad.tcga.pub | 333 | 152 | [14] |
prad.tcga | 498 | 152 | [14] |
Module | Autophagy | Epithelial to Mesenchymal Transition | Phosphatidylethanolamine Binding |
---|---|---|---|
blue | ABL1, ANXA7, ARSB, BNIP1, VPS51, CLTC, DAP, FOXO1, HMGB1, IFI16, NPC1, S100A8, S100A9, STK11, TMBIM6, TP53, UVRAG, SRPX, BECN1, USP10, ULK2, PLEKHM1, TECPR2, HDAC6, OPTN, RNF41, RGS19, ATG7, TM9SF1, WDR45, PARK7, VPS13A, VPS39, ULK3, PTPN22, TMEM208, NRBF2, RAB39A, FNBP1L, WIPI1, MAP1S, DRAM1, SUPT20H, VPS11, TIGAR, VPS18, PHF23, MAP1LC3B, VMP1, C19orf12, ATG10, EVA1A, WDR24, ATG4C, TRIM5, LRSAM1, RAB39B, LRRK2, DRAM2, SMCR8 | BMP2, BMP7, FGFR2, FOXF2, HNRNPAB, RBPJ, LOXL2, S100A4, SNAI2, TGFB1, TGFB2, TGFBR3, WNT5A, DLG5, NOG, DDX17, LEF1, EPB41L5, FAM83D, LOXL3, RFLNB | ANXA11, MFGE8, PLTP, PEMT, CD300A, MAP1LC3A |
brown | CTSD, RAB8A, TBC1D25, PIK3C3, PIK3CB, RAB1A, VCP, TFEB, ULK1, SQSTM1, HAP1, ATG5, NAPSA, RUBCN, TBC1D5, SIRT2, ATG4B, TECPR1, CHMP2B, VPS41, TRIM17, TOLLIP, ZKSCAN3, CHMP4B, RAB12, C9orf72 | AMELX, CTNNB1, HGF, HIF1A, SNAI1, SOX9, TGFBR1, HMGA2 | NF1, PEBP1, ESYT2 |
yellow | ITGB4, PGC, USP13, TMEM59, RB1CC1, GABARAPL2, CLEC16A, UBQLN2, SH3GLB1, WDR41, VTI1A | GSK3B, NOTCH1, WNT11, CUL7, WNT4 |
Family | Protein | Name | Main Function |
---|---|---|---|
WD Repeat Domain | WDR45 | WD Repeat Domain 45 | Frequently mutated in lung adenocarcinomas [15]. |
WIPI1 | WD Repeat Domain, Phosphoinositide Interacting 1 | High expression is associated with survival in hepatocellular carcinoma patients [16]. | |
PI3K | PIK3C3 | Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 | Promote cancer growth through p62 [17]. |
PIK3CB | Phosphatidylinositol-4, 5-Bisphosphate 3-Kinase Catalytic Subunit Beta | Mediates cancer metastasis [18]. | |
TBC | TBC1D5 | TBC1 Domain Family Member 5 | Reduced copy number in breast cancer [19]. |
TBC1D25 | TBC1 Domain Family Member 25 | ||
Other | TOLLIP | Toll Interacting Protein | Hypermethylated in response to sex hormones in prostate cancer cells [20]. |
TGFBR1 | Transforming Growth Factor Beta Receptor 1 | Multiple polymorphisms are associated with cancer development [21]. |
Factor | Name | Function |
---|---|---|
ERCC6 | ERCC Excision Repair 6, Chromatin Remodeling Factor | A DNA-binding protein that is important in transcription-coupled excision repair. Several polymorphisms the gene coding region were associated with susceptibility to development of cancer and chemoresistancy [22,23]. |
VEZF1 | Vascular Endothelial Zinc Finger 1 | A transcriptional regulatory protein that is involved in angiogenesis. Contribute to the epigenetic aberrations and the associated tumorigenesis [24,25]. |
hsa-miR-378c | Close relative (hsa-miR-378a) | Inhibits cell growth and enhances apoptosis in cancer [26]. |
hsa-miR-761 | Enhances cancer growth, migration and invasion [27]. | |
hsa-miR-23c | Close relative (hsa-miR-23a) | Associated with autophagy, loss of RKIP/PEBP1 and multiple tumors [28,29]. |
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Share and Cite
Ahmed, M.; Lai, T.H.; Zada, S.; Hwang, J.S.; Pham, T.M.; Yun, M.; Kim, D.R. Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer. Cancers 2018, 10, 273. https://doi.org/10.3390/cancers10080273
Ahmed M, Lai TH, Zada S, Hwang JS, Pham TM, Yun M, Kim DR. Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer. Cancers. 2018; 10(8):273. https://doi.org/10.3390/cancers10080273
Chicago/Turabian StyleAhmed, Mahmoud, Trang Huyen Lai, Sahib Zada, Jin Seok Hwang, Trang Minh Pham, Miyong Yun, and Deok Ryong Kim. 2018. "Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer" Cancers 10, no. 8: 273. https://doi.org/10.3390/cancers10080273