ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Hepatic Expression of Armcx3 Is Modulated in Response to Nutritional Challenges
2.2. Gene Invalidation of Armcx3 Ameliorates HFD-Induced Metabolic Alterations and Protects against NAFLD
2.3. Inactivation of the Armcx3 Gene Protects Against Hepatic Carcinogenesis
2.4. ARMCX3 Regulates DEN-Induced Apoptotic Death and Macrophage Infiltration
2.5. ARMCX3 Invalidation Does Not Affect Hepatic Mitochondria
2.6. ARMCX3 Affects ERK Signaling in DEN-Induced Tumors from HFD-Fed Mice
2.7. ARMCX3 Invalidation Reduces Cell Viability, Clonality and Migration in Hepatocellular Carcinoma Cell Lines
2.8. ARMCX3 Overexpression In Vitro Induces Hepatocellular Carcinoma Cells Proliferation in a SOX9-Dependent Mechanism
3. Discussion
4. Materials and Methods
4.1. Mice Care
4.2. Human Samples
4.3. ARMCX3-KO Mouse Generation
- Armcx3 S1F: GGGGCGGTGGGCAGGATGACAGC
- Armcx3 S4F: AAGTTCTAGGAATCGAGAGCC
- Armcx3 S: ATCATTTCCCCTTGACTCTGG
- Forward Wt-Cre: CTAGGCCACGAATTGAAAGATCT
- Reverse Wt-Cre: GTAGGTGGAAATTCTAGCATCATCC
- Forward Cre: GCGGTCTGGCAGTAAAAACTATC
- Reverse Cre: GTGAAACAGCATTGCTGTCACTT
4.4. Metabolism-Related Studies
4.5. DEN-Induced Hepatocarcinogenesis
4.6. Mouse Partial Hepatectomy and Acute CCl4 Administration
4.7. Mouse Primary Hepatocytes
4.8. Histology and Immunohistochemistry
4.9. Cell Lines and Culture Conditions
4.10. Transfection of siRNAs
4.11. Armcx3 Overexpression and SOX9 Knockdown In Vitro
4.12. Wound Healing Assay
4.13. Cell Viability Assay
4.14. Clonogenic Assay
4.15. Palmitic Acid and Oleic Acid Treatments
4.16. Western Blotting
4.17. RNA Isolation, cDNA Synthesis, and Real-Time PCR
4.18. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Mirra, S.; Gavaldà-Navarro, A.; Manso, Y.; Higuera, M.; Serrat, R.; Salcedo, M.T.; Burgaya, F.; Balibrea, J.M.; Santamaría, E.; Uriarte, I.; et al. ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity. Cancers 2021, 13, 1110. https://doi.org/10.3390/cancers13051110
Mirra S, Gavaldà-Navarro A, Manso Y, Higuera M, Serrat R, Salcedo MT, Burgaya F, Balibrea JM, Santamaría E, Uriarte I, et al. ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity. Cancers. 2021; 13(5):1110. https://doi.org/10.3390/cancers13051110
Chicago/Turabian StyleMirra, Serena, Aleix Gavaldà-Navarro, Yasmina Manso, Mónica Higuera, Román Serrat, María Teresa Salcedo, Ferran Burgaya, José Maria Balibrea, Eva Santamaría, Iker Uriarte, and et al. 2021. "ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity" Cancers 13, no. 5: 1110. https://doi.org/10.3390/cancers13051110
APA StyleMirra, S., Gavaldà-Navarro, A., Manso, Y., Higuera, M., Serrat, R., Salcedo, M. T., Burgaya, F., Balibrea, J. M., Santamaría, E., Uriarte, I., Berasain, C., Avila, M. A., Mínguez, B., Soriano, E., & Villarroya, F. (2021). ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity. Cancers, 13(5), 1110. https://doi.org/10.3390/cancers13051110