MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Selection of Stably Transfected Clones
2.2. MiR-215-5p Inhibits the Clonogenic Potential, Arrests the Cell Cycle, and Induce Apoptosis of CRC Cells
2.3. MiR-215-5p Inhibits Cell Migration/Invasion of HCT-15 Cells In Vitro
2.4. MiR-215-5p Inhibits CRC Cells Tumor Growth In Vivo
2.5. MiR-215-5p Inhibits the Metastatic Potential of CRC Cells In Vivo
2.6. Possible Molecular Mechanism of Metastatic Process Regulated by miR-215-5p via Involvement of ECM-Receptor Interactions and Focal Adhesion Pathways
2.7. Validation of Potential miR-215-5p Targets
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Cell Culture
4.2. Patient Samples
4.3. Stable Transfection of miR-215
4.4. Colony Forming Aassay
4.5. Cell Cycle, Apoptosis and Cell Death analysis
4.6. Transwell Migration and Invasiveness Assay
4.7. Animal Models
4.8. Tumorigenicity Assay
4.9. Intra-Splenic Metastatic Model
4.10. RNA Isolation
4.11. Reverse Transcription and Quantitative Real-Time PCR
4.12. Transcriptome Profiling
4.13. Statistical Analysis
4.14. Processing of RNA-Seq Data
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
List of Abbreviations
References
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KEGG ID | Number of Genes | Adjusted p-Value | Description |
---|---|---|---|
hsa04512 | 45 | 1.9955 × 10−5 | ECM-receptor interaction |
hsa04510 | 90 | 2.7430 × 10−5 | Focal adhesion |
hsa05412 | 38 | 1.9617 × 10−3 | Arrhythmogenic right ventricular cardiomyopathy |
hsa04151 | 127 | 2.0126 × 10−3 | PI3K-Akt signaling pathway |
hsa00980 | 31 | 2.0813 × 10−3 | Metabolism of xenobiotics by cytochrome P450 |
hsa04950 | 14 | 3.3039 × 10−3 | Maturity onset diabetes of the young |
hsa05200 | 186 | 3.9291 × 10−3 | Pathways in cancer |
hsa05217 | 32 | 4.6798 × 10−3 | Basal cell carcinoma |
hsa00982 | 28 | 4.7884 × 10−3 | Drug metabolism - cytochrome P450 |
hsa04060 | 91 | 4.7884 × 10−3 | Cytokine-cytokine receptor interaction |
Top 10 GO Molecular Functions Terms | ||||
GO ID | Number of Genes | Background Genes | Adjusted p-Value | Term |
GO:0005509 | 235 | 544 | 3.5724 × 10−7 | Calcium ion binding |
GO:0019838 | 58 | 110 | 1.0470 × 10−3 | Growth factor binding |
GO:0003779 | 143 | 336 | 1.0470 × 10−3 | Actin binding |
GO:0005201 | 65 | 129 | 1.0470 × 10−3 | Extracellular matrix structural constituent |
GO:0098772 | 464 | 1282 | 1.2080 × 10−3 | Molecular function regulator |
GO:0015267 | 122 | 282 | 1.2080 × 10−3 | Channel activity |
GO:0022803 | 122 | 282 | 1.2080 × 10−3 | Passive transmembrane transporter activity |
GO:0004714 | 28 | 44 | 1.6820 × 10−3 | Transmembrane receptor protein tyrosine kinase activity |
GO:0005102 | 417 | 1150 | 2.3635 × 10−3 | Signaling receptor binding |
GO:0019199 | 34 | 59 | 3.0812 × 10−3 | Transmembrane receptor protein kinase activity |
Top 10 GO biological processes terms | ||||
GO ID | Number of Genes | Background Genes | Adjusted p-Value | Term |
GO:0048856 | 1729 | 4694 | 3.4494 × 10−25 | Anatomical structure development |
GO:0032501 | 2074 | 5804 | 2.8832 × 10−24 | Multicellular organismal process |
GO:0048731 | 1451 | 3876 | 3.4175 × 10−23 | System development |
GO:0007275 | 1593 | 4320 | 6.2510 × 10−23 | Multicellular organism development |
GO:0032502 | 1811 | 5012 | 2.1700 × 10−22 | Developmental process |
GO:0030154 | 1225 | 3234 | 1.0946 × 10−20 | Cell differentiation |
GO:0009653 | 858 | 2152 | 3.8805 × 10−20 | Anatomical structure morphogenesis |
GO:0040011 | 607 | 1436 | 6.4324 × 10−20 | Locomotion |
GO:0051239 | 1005 | 2592 | 9.4443 × 10−20 | Regulation of multicellular organismal process |
GO:0048869 | 1266 | 3380 | 1.3098 × 10−19 | Cellular developmental process |
Top 10 GO cellular components terms | ||||
GO ID | Number of Genes | Background Genes | Adjusted p-Value | Term |
GO:0071944 | 1512 | 3934 | 2.7470 × 10−32 | Cell periphery |
GO:0005886 | 1484 | 3853 | 2.7470 × 10−32 | Plasma membrane |
GO:0044459 | 773 | 1916 | 4.0527 × 10−20 | Plasma membrane part |
GO:0044425 | 1723 | 4911 | 8.8179 × 10−15 | Membrane part |
GO:0031224 | 1351 | 3755 | 1.7922 × 10−14 | Intrinsic component of membrane |
GO:0098590 | 412 | 976 | 2.1436 × 10−13 | Plasma membrane region |
GO:0016021 | 1300 | 3640 | 1.2325 × 10−12 | Integral component of membrane |
GO:0005576 | 1188 | 3298 | 1.7219 × 10−12 | Extracellular region |
GO:0016020 | 2454 | 7347 | 5.7937 × 10−12 | Membrane |
GO:0005911 | 177 | 373 | 4.0630 × 10−10 | Cell-cell junction |
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Machackova, T.; Vychytilova-Faltejskova, P.; Souckova, K.; Trachtova, K.; Brchnelova, D.; Svoboda, M.; Kiss, I.; Prochazka, V.; Kala, Z.; Slaby, O. MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion. Cancers 2020, 12, 3518. https://doi.org/10.3390/cancers12123518
Machackova T, Vychytilova-Faltejskova P, Souckova K, Trachtova K, Brchnelova D, Svoboda M, Kiss I, Prochazka V, Kala Z, Slaby O. MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion. Cancers. 2020; 12(12):3518. https://doi.org/10.3390/cancers12123518
Chicago/Turabian StyleMachackova, Tana, Petra Vychytilova-Faltejskova, Kamila Souckova, Karolina Trachtova, Dominika Brchnelova, Marek Svoboda, Igor Kiss, Vladimir Prochazka, Zdenek Kala, and Ondrej Slaby. 2020. "MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion" Cancers 12, no. 12: 3518. https://doi.org/10.3390/cancers12123518