Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Differential Expression of ZNF518B Isoforms in CRC Patients
2.2. Overexpression of ZNF518B in RKO Cells
2.3. Functional Interactions of ZNF518B
2.4. Molecular Mechanisms Involved in the Oncogenic Properties of ZNF518B
2.5. Genes Affected in Common by the Silencing of ZNF518B, EHMT2 and EZH2 in HCT116 Cells
2.6. Recruitment of Inhibitory Histone Methyltransferases by ZNF518B
3. Discussion
4. Materials and Methods
4.1. Human CRC Samples
4.2. Cell Culture
4.3. ZNF518B Overexpression and Knocking Down
4.4. Phenotypic Analyses of Transformed Cells
4.5. Immunocytochemistry
4.6. Microarray Analysis of Gene Expression
4.7. In Silico Analysis of the Effects of EHMT2 and EZH2 Silencing
4.8. Protein–Protein Interaction Network
4.9. Chromatin Immunoprecipitation (ChIP)
4.10. Quantitative PCR Analysis
4.11. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Riffo-Campos, Á.; Castillo, J.; Vallet-Sánchez, A.; Ayala, G.; Cervantes, A.; López-Rodas, G.; Franco, L. In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells. Oncol. Rep. 2016, 36, 3627–3634. [Google Scholar] [CrossRef] [Green Version]
- Jin, T.; Ren, Y.; Shi, X.; Jiri, M.; He, N.; Feng, T.; Yuan, D.; Kang, L. Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets. Rheumatol. Int. 2015, 35, 1141–1147. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.Y.; Geng, T.T.; Liu, L.J.; Yuan, D.Y.; Feng, T. SLC2A9 and ZNF518B polymorphisms correlate with gout-related metabolic indices in Chinese Tibetan populations. Genet. Mol. Res. 2015, 14, 9915–9921. [Google Scholar] [CrossRef] [PubMed]
- Köttgen, A.; Albrecht, E.; Teumer, A.; Vitart, V.; Krumsiek, J.; Hundertmark, C.; Pistis, G.; Ruggiero, D.; O’Seaghdha, C.M.; Haller, T.; et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat. Genet. 2013, 45, 145–154. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ding, R.; Yang, M.; Quan, J.; Li, S.; Zhuang, Z.; Zhou, S.; Zheng, E.; Hong, L.; Li, Z.; Cai, G.; et al. Single-locus and multi-locus genome-wide association studies for intramuscular fat in Duroc pigs. Front. Genet. 2019, 10, 619. [Google Scholar] [CrossRef] [PubMed]
- Bacos, K.; Gillberg, L.; Volkov, P.; Olsson, A.H.; Hansen, T.; Pedersen, O.; Gjesing, A.P.; Eiberg, H.; Tuomi, T.; Almgren, P.; et al. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes. Nat. Commun. 2016, 7, 11089. [Google Scholar] [CrossRef] [Green Version]
- Maier, V.K.; Feeney, C.M.; Taylor, J.E.; Creech, A.L.; Qiao, J.W.; Szanto, A.; Das, P.P.; Chevrier, N.; Cifuentes-Rojas, C.; Orkin, S.H.; et al. Functional proteomic analysis of repressive histone methyltransferase complexes reveals ZNF518B as a G9A regulator. Mol. Cell. Proteom. 2015, 14, 1435–1446. [Google Scholar] [CrossRef] [Green Version]
- Zhang, J.; He, P.; Xi, Y.; Geng, M.; Chen, Y.; Ding, J. Down-regulation of G9a triggers DNA damage response and inhibits colorectal cancer cells proliferation. Oncotarget 2015, 6, 2917–2927. [Google Scholar] [CrossRef] [Green Version]
- Gimeno-Valiente, F.; Riffo-Campos, Á.L.; Vallet-Sánchez, A.; Siscar-Lewin, S.; Gambardella, V.; Tarazona, N.; Cervantes, A.; Franco, L.; Castillo, J.; López-Rodas, G. ZNF518B gene up-regulation promotes dissemination of tumour cells and is governed by epigenetic mechanisms in colorectal cancer. Sci. Rep. 2019, 9, 9339. [Google Scholar] [CrossRef]
- Coltri, P.P.; dos Santos, M.G.P.; da Silva, G.H.G. Splicing and cancer: Challenges and opportunities. Wiley Interdiscip. Rev. RNA 2019, 10, e1527. [Google Scholar] [CrossRef]
- Adler, A.S.; McCleland, M.L.; Yee, S.; Yaylaoglu, M.; Hussain, S.; Cosino, E.; Quinones, G.; Modrusan, Z.; Seshagiri, S.; Torres, E.; et al. An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth. Genes Dev. 2014, 28, 1068–1084. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, J.C.; Lee, Y.C.; Liang, Y.C.; Fann, Y.C.; Johnson, K.R.; Lin, Y.J. The impact of the RBM4-initiated splicing cascade on modulating the carcinogenic signature of colorectal cancer cells. Sci. Rep. 2017, 7, 44204. [Google Scholar] [CrossRef] [PubMed]
- Ling, Y.; Kuang, Y.; Chen, L.L.; Lao, W.F.; Zhu, Y.R.; Wang, L.Q.; Wang, D. A novel RON splice variant lacking exon 2 activates the PI3K/ AKT pathway via PTEN phosphorylation in colorectal carcinoma cells. Oncotarget 2017, 8, 39101–39116. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, J.; Li, H.; Shen, S.; Sun, L.; Yuan, Y.; Xing, C. Alternative splicing events implicated in carcinogenesis and prognosis of colorectal cancer. J. Cancer 2018, 9, 1754–1764. [Google Scholar] [CrossRef] [Green Version]
- Liu, Y.; Huang, W.; Gao, X.; Kuang, F. Regulation between two alternative splicing isoforms ZNF148 FL and ZNF148 ΔN, and their roles in the apoptosis and invasion of colorectal cancer. Pathol. Res. Pract. 2019, 215, 272–277. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Wang, Y.; Liu, Y.; Zhang, C.; Luo, Y.; Guo, R.; Zhan, Z.; Wei, N.; Xie, Z.; Shen, L.; et al. U2-related proteins CHERP and SR140 contribute to colorectal tumorigenesis via alternative splicing regulation. Int. J. Cancer 2019, 145, 2728–2739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Balsamo, M.; Mondal, C.; Carmona, G.; McClain, L.M.; Riquelme, D.N.; Tadros, J.; Ma, D.; Vasile, E.; Condeelis, J.S.; Lauffenburger, D.A.; et al. The alternatively-included 11a sequence modifies the effects of Mena on actin cytoskeletal organization and cell behavior. Sci. Rep. 2016, 6, 35298. [Google Scholar] [CrossRef] [PubMed]
- Kong, J.; Sun, W.; Li, C.; Wan, L.; Wang, S.; Wu, Y.; Xu, E.; Zhang, H.; Lai, M. Long non-coding RNA LINC01133 inhibits epithelial–mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6. Cancer Lett. 2016, 380, 476–484. [Google Scholar] [CrossRef]
- Wang, Z.N.; Liu, D.; Yin, B.; Ju, W.Y.; Qiu, H.Z.; Xiao, Y.; Chen, Y.J.; Peng, X.Z.; Lu, C.M. High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin. Oncotarget 2017, 8, 36185–36202. [Google Scholar] [CrossRef] [Green Version]
- Lin, J.C.; Lee, Y.C.; Tan, T.H.; Liang, Y.C.; Chuang, H.C.; Fann, Y.C.; Johnson, K.R.; Lin, Y.J. RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell. Biochim. Biophys. Acta Mol. Cell Res. 2018, 1865, 259–272. [Google Scholar] [CrossRef]
- Sakuma, K.; Sasaki, E.; Kimura, K.; Komori, K.; Shimizu, Y.; Yatabe, Y.; Aoki, M. HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition. Gut 2018, 67, 1103–1111. [Google Scholar] [CrossRef]
- Devaud, C.; Tilkin-Mariamé, A.F.; Vignolle-Vidoni, A.; Souleres, P.; Denadai-Souza, A.; Rolland, C.; Duthoit, C.; Blanpied, C.; Chabot, S.; Bouillé, P.; et al. FAK alternative splice mRNA variants expression pattern in colorectal cancer. Int. J. Cancer 2019, 145, 494–502. [Google Scholar] [CrossRef] [Green Version]
- Zhao, Y.J.; Han, H.Z.; Liang, Y.; Shi, C.Z.; Zhu, Q.C.; Yang, J. Alternative splicing of VEGFA, APP and NUMB genes in colorectal cancer. World J. Gastroenterol. 2015, 21, 6550–6560. [Google Scholar] [CrossRef] [PubMed]
- Deloria, A.J.; Höflmayer, D.; Kienzl, P.; Lopatecka, J.; Sampl, S.; Klimpfinger, M.; Braunschmid, T.; Bastian, F.; Lu, L.; Marian, B.; et al. Epithelial splicing regulatory protein 1 and 2 paralogues correlate with splice signatures and favorable outcome in human colorectal cancer. Oncotarget 2016, 7, 73800–73816. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Komor, M.A.; Pham, T.V.; Hiemstra, A.C.; Piersma, S.R.; Bolijn, A.S.; Schelfhorst, T.; Delis-Van Diemen, P.M.; Tijssen, M.; Sebra, R.P.; Ashby, M.; et al. Identification of differentially expressed splice variants by the proteogenomic pipeline splicify. Mol. Cell. Proteom. 2017, 16, 1850–1863. [Google Scholar] [CrossRef] [Green Version]
- Köger, N.; Brieger, A.; Hinrichsen, I.M.; Zeuzem, S.; Plotz, G. Analysis of MUTYH alternative transcript expression, promoter function, and the effect of human genetic variants. Hum. Mutat. 2019, 40, 472–482. [Google Scholar] [CrossRef] [PubMed]
- Annalora, A.J.; Jozic, M.; Marcus, C.B.; Iversen, P.L. Alternative splicing of the vitamin D receptor modulates target gene expression and promotes ligand-independent functions. Toxicol. Appl. Pharmacol. 2019, 364, 35298. [Google Scholar] [CrossRef]
- Takahashi, H.; Nishimura, J.; Kagawa, Y.; Kano, Y.; Takahashi, Y.; Wu, X.; Hiraki, M.; Hamabe, A.; Konno, M.; Haraguchi, N.; et al. Significance of polypyrimidine tract-binding protein 1 expression in colorectal cancer. Mol. Cancer Ther. 2015, 14, 1705–1716. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wan, L.; Yu, W.; Shen, E.; Sun, W.; Liu, Y.; Kong, J.; Wu, Y.; Han, F.; Zhang, L.; Yu, T.; et al. SRSF6-regulated alternative splicing that promotes tumour progression offers a therapy target for colorectal cancer. Gut 2019, 68, 118–129. [Google Scholar] [CrossRef]
- Tarazona, N.; Gimeno-Valiente, F.; Gambardella, V.; Zuñiga, S.; Rentero-Garrido, P.; Huerta, M.; Roselló, S.; Martinez-Ciarpaglini, C.; Carbonell-Asins, J.A.; Carrasco, F.; et al. Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer. Ann. Oncol. 2019, 30, 1804–1812. [Google Scholar] [CrossRef] [Green Version]
- Chang, X.; Chai, Z.; Zou, J.; Wang, H.; Wang, Y.; Zheng, Y.; Wu, H.; Liu, C. PADI3 induces cell cycle arrest via the Sirt2/AKT/p21 pathway and acts as a tumor suppressor gene in colon cancer. Cancer Biol. Med. 2019, 16, 729–742. [Google Scholar] [PubMed]
- Peng, C.; Zhang, Z.; Wu, J.; Lv, Z.; Tang, J.; Xie, H.; Zhou, L.; Zheng, S. A critical role for ZDHHC2 in metastasis and recurrence in human hepatocellular carcinoma. BioMed Res. Int. 2014, 2014, 832712. [Google Scholar] [CrossRef]
- Park, H.J.; Kim, S.H.; Moon, D.O. Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4. Oncol. Lett. 2017, 13, 4357–4363. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, T.H.; Chang, J.L.; Ho, J.Y.; Wu, H.C.; Chen, T.C. EphrinA5 suppresses colon cancer development by negatively regulating epidermal growth factor receptor stability. FEBS J. 2012, 279, 251–263. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Hou, X.; Wu, C.; Han, L.; Li, Q.; Wang, J.; Luo, S. MiR-645 promotes invasiveness, metastasis and tumor growth in colorectal cancer by targeting EFNA5. Biomed. Pharmacother. 2020, 125, 109889. [Google Scholar] [CrossRef]
- Jia, Y.L.; Xu, M.; Dou, C.W.; Liu, Z.K.; Xue, Y.M.; Yao, B.W.; Ding, L.L.; Tu, K.S.; Zheng, X.; Liu, Q.G. P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy. Cell Death Dis. 2016, 7, e2400. [Google Scholar] [CrossRef] [Green Version]
- Barski, A.; Cuddapah, S.; Cui, K.; Roh, T.Y.; Schones, D.E.; Wang, Z.; Wei, G.; Chepelev, I.; Zhao, K. High-resolution profiling of histone methylations in the human genome. Cell 2007, 129, 823–837. [Google Scholar] [CrossRef] [Green Version]
- Pan, M.R.; Hsu, M.C.; Chen, L.T.; Hung, W.C. Orchestration of H3K27 methylation: Mechanisms and therapeutic implication. Cell. Mol. Life Sci. 2018, 75, 209–223. [Google Scholar] [CrossRef] [Green Version]
- Guinney, J.; Dienstmann, R.; Wang, X.; de Reyniès, A.; Schlicker, A.; Soneson, C.; Marisa, L.; Roepman, P.; Nyamundanda, G.; Angelino, P.; et al. The consensus molecular subtypes of colorectal cancer. Nat. Med. 2015, 21, 1350–1356. [Google Scholar] [CrossRef]
- Yun, D.; Wang, H.; Wang, Y.; Chen, Y.; Zhao, Z.; Ma, J.; Ji, Y.; Huang, Q.; Chen, J.; Chen, H.; et al. Shuttling SLC2A4RG is regulated by 14-3-3θ to modulate cell survival via caspase-3 and caspase-6 in human glioma. EBioMedicine 2019, 40, 163–175. [Google Scholar] [CrossRef] [Green Version]
- Ji, Q.; Cai, G.; Liu, X.; Zhang, Y.; Wang, Y.; Zhou, L.; Sui, H.; Li, Q. MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 in colorectal cancer metastasis. Cell Death Dis. 2019, 10, 378. [Google Scholar] [CrossRef]
- Payne, A.W.; Pant, D.K.; Pan, T.C.; Chodosh, L.A. Ceramide kinase promotes tumor cell survival and mammary tumor recurrence. Cancer Res. 2014, 74, 6352–6363. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nakahara, I.; Miyamoto, M.; Shibata, T.; Akashi-Tanaka, S.; Kinoshita, T.; Mogushi, K.; Oda, K.; Ueno, M.; Takakura, N.; Mizushima, H.; et al. Up-regulation of PSF1 promotes the growth of breast cancer cells. Genes Cells 2010, 15, 1015–1024. [Google Scholar] [CrossRef] [PubMed]
- Lian, Y.F.; Li, S.S.; Huang, Y.L.; Wei, H.; Chen, D.M.; Wang, J.L.; Huang, Y.H. Up-regulated and interrelated expressions of GINS subunits predict poor prognosis in hepatocellular carcinoma. Biosci. Rep. 2018, 38, BSR20181178. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodríguez-Paredes, M.; Esteller, M. Cancer epigenetics reaches mainstream oncology. Nat. Med. 2011, 17, 330–339. [Google Scholar] [CrossRef]
- Feng, S.; De Carvalho, D.D. Clinical advances in targeting epigenetics for cancer therapy. FEBS J. 2021. [Google Scholar] [CrossRef]
- Avgustinova, A.; Symeonidi, A.; Castellanos, A.; Urdiroz-Urricelqui, U.; Solé-Boldo, L.; Martín, M.; Pérez-Rodríguez, I.; Prats, N.; Lehner, B.; Supek, F.; et al. Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours. Nat. Cell Biol. 2018, 20, 1400–1409. [Google Scholar] [CrossRef]
- Rowbotham, S.P.; Li, F.; Dost, A.F.M.; Louie, S.M.; Marsh, B.P.; Pessina, P.; Anbarasu, C.R.; Brainson, C.F.; Tuminello, S.J.; Lieberman, A.; et al. H3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression. Nat. Commun. 2018, 9, 4559. [Google Scholar] [CrossRef]
- Tarazona, N.; Gimeno-Valiente, F.; Gambardella, V.; Huerta, M.; Roselló, S.; Zuniga, S.; Calon, A.; Carbonell-Asins, J.A.; Fontana, E.; Martinez-Ciarpaglini, C.; et al. Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer. ESMO Open 2020, 5, e000847. [Google Scholar] [CrossRef]
- Ohtani, H.; Liu, M.; Zhou, W.; Liang, G.; Jones, P.A. Switching roles for DNA and histone methylation depend on evolutionary ages of human endogenous retroviruses. Genome Res. 2018, 28, 1147–1157. [Google Scholar] [CrossRef] [Green Version]
- Andrews, S. FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http://www.bioinformatics.babraham.ac.uk/projects/fastqc (accessed on 15 February 2021).
- Dobin, A.; Davis, C.A.; Schlesinger, F.; Drenkow, J.; Zaleski, C.; Jha, S.; Batut, P.; Chaisson, M.; Gingeras, T.R. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 2013, 29, 15–21. [Google Scholar] [CrossRef]
- Langmead, B.; Salzberg, S.L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 2012, 9, 357–359. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McCarthy, D.J.; Chen, Y.; Smyth, G.K. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 2012, 40, 4288–4297. [Google Scholar] [CrossRef] [Green Version]
- Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019, 47, D607–D613. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software Environment for integrated models of biomolecular interaction networks. Genome Res. 2003, 13, 2498–2504. [Google Scholar] [CrossRef]
- Tur, G.; Georgieva, E.; Gagete, A.; López-Rodas, G.; Rodríguez, J.; Franco, L. Factor binding and chromatin modification in the promoter of murine Egr1 gene upon induction. Cell. Mol. Life Sci. 2010, 4065–4077. [Google Scholar] [CrossRef] [PubMed]
- Sandoval, J.; Rodríguez, J.L.; Tur, G.; Serviddio, G.; Pereda, J.; Boukaba, A.; Sastre, J.; Torres, L.; Franco, L.; López-Rodas, G. RNAPol-ChIP: A novel application of chromatin immunoprecipitation to the analysis of real-time gene transcription. Nucleic Acids Res. 2004, 32, e88. [Google Scholar] [CrossRef] [Green Version]
- Györffy, B.; Lanczky, A.; Eklund, A.C.; Denkert, C.; Budczies, J.; Li, Q.; Szallasi, Z. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1809 patients. Breast Cancer Res. Treat. 2010, 123, 725–731. [Google Scholar] [CrossRef] [Green Version]
- Nagy, A.; Munkacsy, G.; Györffy, B. Pancancer survival analysis of cancer hallmark genes. Sci. Rep. 2021, 11, 6047. [Google Scholar] [CrossRef]
Biological Pathway | Up-Regulated Genes (n) | Down-Regulated Genes (n) |
---|---|---|
EGFR pathway | 14 | 14 |
Signalling VEGFR2 | 16 | 27 |
PI3K-AKT pathway | 26 | 17 |
MAPK pathway | 21 | 18 |
WNT pathway | 8 | 9 |
TGF-β signalling pathway | 13 | 13 |
RAS pathway | 16 | 8 |
Biological processes | Up-regulated genes (n) | Down-regulated genes (n) |
Cell cycle | 9 | 20 |
EMT in CRC | 12 | 9 |
Apoptosis | 8 | 12 |
Histone modification | 4 | 13 |
Focal adhesion | 20 | 9 |
Focal adhesion via PI3K-AKT-mTOR | 25 | 13 |
Only the genes related to cancer-linked processes are included. |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gimeno-Valiente, F.; Riffo-Campos, Á.L.; Torres, L.; Tarazona, N.; Gambardella, V.; Cervantes, A.; López-Rodas, G.; Franco, L.; Castillo, J. Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer. Cancers 2021, 13, 1433. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13061433
Gimeno-Valiente F, Riffo-Campos ÁL, Torres L, Tarazona N, Gambardella V, Cervantes A, López-Rodas G, Franco L, Castillo J. Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer. Cancers. 2021; 13(6):1433. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13061433
Chicago/Turabian StyleGimeno-Valiente, Francisco, Ángela L. Riffo-Campos, Luis Torres, Noelia Tarazona, Valentina Gambardella, Andrés Cervantes, Gerardo López-Rodas, Luis Franco, and Josefa Castillo. 2021. "Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer" Cancers 13, no. 6: 1433. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13061433