Promoter methylation and expression of SOCS-1 affect clinical outcome and epithelial-mesenchymal transition in colorectal cancer |
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| Institution: | 1. Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China;2. Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China;3. Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China;4. Department of Medical Oncology, Jingmen Traditional Chinese Medicine Hospital, No.15, Baimiao Rd, Jingmen, Hubei 448000, PR China;1. Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska (CCK) R8:04, Stockholm SE-171 76, Sweden;2. Université Pierre et Marie Curie, Paris, France;3. INSERM U1138, Centre de Recherche des Cordeliers, Paris, France;4. Equipe11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France;5. Université Paris Descartes, Paris, France;6. Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France;7. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France;8. Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden;1. Erasmus Medical Center, University Medical Center Rotterdam, Department of Public Health, P.O. Box 2040, 3000CA, Rotterdam, The Netherlands;2. Erasmus Medical Center, University Medical Center Rotterdam, Department of Pulmonary Medicine, P.O. Box 2040, 3000CA, Rotterdam, The Netherlands;3. Amphia Hospital Breda, Department of Pulmonary Medicine, P.O. box 90158, The Netherlands;4. Maasstad Hospital Rotterdam, Department of Pathology, P.O. box 9100, The Netherlands;1. Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan;2. Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523, Japan;3. Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan;4. Department of Microbiology, National University of Singapore, Singapore;2. Université Paris-Est Créteil, Créteil, France;3. CNRS UMR3244, Centre de Recherche, Institut Curie, Paris, France;4. Département de Pathologie, Plateforme de Ressources Biologiques, Hôpital H. Mondor-A. Chenevier, AP-HP, Créteil, France;5. Faculté de Médecine/Signalisation et Cancer de la Prostate/EA4438, Université Strasbourg, Strasbourg, France;1. Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Canada;2. Department of Nutrition, University of Montreal, Montreal, QC H3T 1J4, Canada;3. Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada;4. Department of Biochemistry, University of Montreal, Montreal, QC H3T 1J4, Canada;5. Department of Pathology and Cell Biology, University of Montreal, Montreal, QC H3T 1J4, Canada |
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| Abstract: | BackgroundAbnormal DNA methylation can cause gene silencing in colorectal cancer (CRC) patients. A gene that is suspected to have a crucial role in various types of cancers is the suppressor of cytokine signaling 1 (SOCS-1). Thus, this study will analyze the ramifications of SOCS-1 promoter methylation in CRC patients. This study will also test the therapeutic effects of hypomethylation as a possible CRC therapy.MethodsFirst, 97CRC patients’ tumor and adjacent normal tissues were collected. Next, the methylation status of the SOCS-1 promoter region was assessed by methylation-specific polymerase chain reaction (MS-PCR); SOCS-1 protein and mRNA expression were also measured. A 48-month median follow-up period was used for the survival analysis of research participants. Lastly, to analyze the changes in cell invasion and migration in conjunction with protein and mRNA expression, the demethylating agent 5-azacytidine was applied in vitro to human CRC cells.ResultsThe results showed increased SOCS-1 hypermethylation in CRC samples compared to controls. Methylated SOCS-1 was associated with significant suppression of SOCS-1 expression in tumors. Additionally, SOCS-1 hypermethylation was significantly correlated with lymph node metastasis and TNM stage. The study also found a poor overall survival rate to be significantly correlated with reduced expression of SOCS-1. After 5-azacytidine treatment, reduced in vitro DNA methylation and increased SOCS-1 expression were observed, and decreased cell migration and epithelial-mesenchymal transition biomarker expression alteration were further confirmed.ConclusionsIn colorectal cancer tissues, the rate of methylation in the SOCS-1 promoter region is high. Through promoter hypermethylation, the SOCS-1 gene was severely down-regulated in the CRC tissue samples, thereby revealing a plausible therapeutic target for CRC therapy. |
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| Keywords: | Colorectal cancer Methylation Suppressor of cytokine signaling Migration Epithelial-mesenchymal transition |
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