RETRACTED ARTICLE: Transcriptional repression of SOCS3 mediated by IL-6/STAT3 signaling via DNMT1 promotes pancreatic cancer growth and metastasis
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Background: Previous studies have investigated the sustained aberrantly activated Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for pancreatic cancer growth and metastasis. Suppressor of cytokine signaling 3 (SOCS3), as a key negative feedback regulator of this signaling pathway, is usually down-regulated in various cancers. In the present study, we aim at exploring the biological function and the underlying molecular regulation mechanisms of SOCS3 in pancreatic cancer. Methods: The expression of SOCS3 and other genes in pancreatic cancer was examined by Quantitative real-time PCR, western blotting and immunohistochemical staining. The interaction between pSTAT3 and DNA Methyltransferase 1 (DNMT1) was investigated by co-immunoprecipitation assay. Luciferase reporter assay was used to investigate the transcriptional regulation of pSTAT3 and DNMT1 on the SOCS3 gene. The effects of SOCS3 on the biological behavior of pancreatic cancer cells were assessed both in vitro and vivo. Furthermore, we performed a comprehensive analysis of the expression of SOCS3 in a pancreatic cancer tissue microarray (TMA) and correlated our findings with pathological parameters and outcomes of the patients. Results: We showed that SOCS3 expression was decreased in phosphorylated STAT3 (pSTAT3)-positive tumors and was negatively correlated with pSTAT3 in pancreatic cancer cells. We also found that IL-6/STAT3 promoted SOCS3 promoter hypermethylation by increasing DNMT1 activity; silencing DNMT1 or 5-aza-2-deoxycytidine (5-AZA) treatment could reverse the down-regulation of SOCS3 mediated by IL-6. Using co-immunoprecipitation and luciferase reporter assays, we found that STAT3 recruited DNMT1 to the promoter region of SOCS3 and inhibited its transcriptional activity. Overexpression of SOCS3 significantly inhibited cell proliferation, which may be due to the increase in G1-S phase arrest; overexpression of SOCS3 also inhibited cell migration and invasion as well as tumorigenicity in nude mice. Pancreatic cancer tissue microarray analysis showed that high SOCS3 expression was a good prognostic factor and negatively correlated with tumor volume and metastasis. Conclusion: We demonstrated that activated IL-6/STAT3 signaling could induce SOCS3 methylation via DNMT1, which led to pancreatic cancer growth and metastasis. These data also provided a mechanistic link between sustained aberrantly activated IL-6/STAT3 signaling and SOCS3 down-regulation in pancreatic cancer. Thus, inhibitors of STAT3 or DNMT1 may become novel strategies for treating pancreatic cancer.
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At the molecular level, IL-6 increases the activity of DNMT1 with activating effects on JAK/STAT3, NF-κB and PI3K/AKT/mTOR signaling pathways, affecting regulation of autophagy-related functions required to maintain cellular homeostasis under stress such as a prenatal insult.
“At the molecular level, IL-6 increases the activity of DNA methyltransferases 1 (DNMT1) with activating effects on the JAK/STAT3, NF-κB and PI3K/AKT/mTOR signaling pathways [144–148] affecting the regulation of autophagy-related functions, that are required to maintain cellular homeostasis under stress [149], such as a prenatal insult.”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [145]
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Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111 · see citing works
Spencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202 · see citing works
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383 · see citing works
Hidalgo, M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0901557 · Cited by 2,570 · see citing works
Revisiting STAT3 signalling in cancer: new and unexpected biological functions
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3818 · Cited by 2,137 · see citing works
Bollrath, J., Phesse, T. J., von Burstin, V. A., Putoczki, T., Bennecke, M., Bateman, T., Nebelsiek, T., Lundgren-May, T., Canli, Ö., Schwitalla, S., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.002 · Cited by 946 · see citing works
Lesina, M., Kurkowski, M. U., Ludes, K., Rose-John, S., Treiber, M., Klöppel, G., Yoshimura, A., Reindl, W., Sipos, B., Akira, S., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.03.009 · Cited by 862 · see citing works
Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue
Yuan, Z.-L., Guan, Y.-J., Chatterjee, D., & Chin, Y. E. (2005) · Science · doi:10.1126/science.1105166 · Cited by 790 · see citing works
Mauer, J., Chaurasia, B., Goldau, J., Vogt, M. C., Ruud, J., Nguyen, K. D., Theurich, S., Hausen, A. C., Schmitz, J., Brönneke, H. S., et al. (2014) · Nature Immunology · doi:10.1038/ni.2865 · Cited by 727 · see citing works
Wan, S., Zhao, E., Kryczek, I., Vatan, L., Sadovskaya, A., Ludema, G., Simeone, D. M., Zou, W., & Welling, T. H. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.08.039 · Cited by 676 · see citing works
Senn, J. J., Klover, P. J., Nowak, I. A., Zimmers, T. A., Koniaris, L. G., Furlanetto, R. W., & Mooney, R. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210689200 · Cited by 620 · see citing works
Wei, D., Le, X., Zheng, L., Wang, L., Frey, J. A., Gao, A. C., Peng, Z., Huang, S., Xiong, H. Q., Abbruzzese, J. L., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1206122 · Cited by 558 · see citing works
Stat3 and MMP7 Contribute to Pancreatic Ductal Adenocarcinoma Initiation and Progression
Fukuda, A., Wang, S. C., Morris, J. P., Folias, A. E., Liou, A., Kim, G. E., Akira, S., Boucher, K., Firpo, M., Mulvihill, S., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.03.002 · Cited by 531 · see citing works
STAT3 as a target for inducing apoptosis in solid and hematological tumors
Siddiquee, K., & Turkson, J. (2008) · Cell Research · doi:10.1038/cr.2008.18 · Cited by 488 · see citing works
Niwa, Y., Kanda, H., Shikauchi, Y., Saiura, A., Matsubara, K., Kitagawa, T., Yamamoto, J., Kubo, T., & Yoshikawa, H. (2005) · Oncogene · doi:10.1038/sj.onc.1208788 · Cited by 358 · see citing works
Hino, R., Uozaki, H., Murakami, N., Ushiku, T., Shinozaki‐Ushiku, A., Ishikawa, S., Morikawa, T., Nakaya, T., Sakatani, T., Takada, K., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3070 · Cited by 344 · see citing works
Auernhammer, C. J., Bousquet, C., & Melmed, S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6964 · Cited by 284 · see citing works
Zhang, Q., Wang, H. Y., Marzec, M., Raghunath, P. N., Nagasawa, T., & Wasik, M. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501959102 · Cited by 263 · see citing works
Cooperation between STAT3 and c-Jun Suppresses Fas Transcription
Ivanov, V. N., Bhoumik, A., Ma, K., Raz, R., Owen‐Schaub, L. B., Levy, D. E., Horvath, C. M., & Ronai, Z. A. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00199-x · Cited by 244 · see citing works
Wehbe, H., Henson, R., Meng, F., Mize-Berge, J., & Patel, T. C. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-2130 · Cited by 224 · see citing works
Inflammatory networks and immune surveillance of pancreatic carcinoma
Vonderheide, R. H., & Bayne, L. J. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.01.006 · Cited by 200 · see citing works
Shain, K. H., Yarde, D. N., Meads, M. B., Huang, M., Jove, R., Hazlehurst, L., & Dalton, W. S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2419 · Cited by 200 · see citing works
Interleukin‐6 promotes tumorigenesis by altering DNA methylation in oral cancer cells
Gasche, J. A., Hoffmann, J., Boland, C. R., & Goel, A. (2011) · International Journal of Cancer · doi:10.1002/ijc.25764 · Cited by 178 · see citing works
High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma
Liao, R., Sun, J., Wu, H., Yi, Y., Wang, J., He, H.-W., Cai, X., Zhou, J., Cheng, Y., Fan, J., et al. (2013) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-32-3 · Cited by 173 · see citing works
Liu, C., Lin, J., Hsu, T., Su, K., Li, A. F., Hsu, H., & Hung, S. (2015) · International Journal of Cancer · doi:10.1002/ijc.29033 · Cited by 169 · see citing works
Minamoto, S., Ikegame, K., Ueno, K., Narazaki, M., Naka, T., Yamamoto, H., Matsumoto, T., Saito, H., Hosoe, S., & Kishimoto, T. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7080 · Cited by 164 · see citing works
Li, Y., Deuring, J. J., Peppelenbosch, M. P., Kuipers, E. J., de Haar, C. G., & van der Woude, C. J. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs214 · Cited by 137 · see citing works
Stauffer, J. K., Scarzello, A. J., Jiang, Q., & Wiltrout, R. H. (2012) · Hepatology · doi:10.1002/hep.25674 · Cited by 132 · see citing works
Pancreatic cancer: A comprehensive review and update
Muniraj, T., Jamidar, P. A., & Aslanian, H. R. (2013) · Disease-a-Month · doi:10.1016/j.disamonth.2013.08.001 · Cited by 130 · see citing works
Interleukin-6: a villain in the drama of pancreatic cancer development and progression
Holmer, R., Goumas, F. A., Waetzig, G. H., Rose‐John, S., & Kalthoff, H. (2014) · Hepatobiliary & pancreatic diseases international · doi:10.1016/s1499-3872(14)60259-9 · Cited by 108 · see citing works
Huang, X., Dai, S., Dai, J., Xiao, Y., Bai, Y., Chen, B., & Zhou, M. (2015) · OncoTargets and Therapy · doi:10.2147/ott.s91511 · Cited by 103 · see citing works
Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3
Denson, L. A., Held, M. A., Menon, R. K., Frank, S. J., Parlow, A. F., & Arnold, D. L. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00178.2002 · Cited by 97 · see citing works
Analysis of DNA methylation and gene expression in radiation-resistant head and neck tumors
Chen, X., Liu, L., Mims, J., Punska, E. C., Williams, K. E., Zhao, W., Arcaro, K. F., Tsang, A. W., Zhou, X., & Furdui, C. M. (2015) · Epigenetics · doi:10.1080/15592294.2015.1048953 · Cited by 82 · see citing works
Epigenetic silencing of SOCS3 identifies a subset of prostate cancer with an aggressive behavior
Pierconti, F., Martini, M., Pinto, F., Cenci, T., Capodimonti, S., Calarco, A., Bassi, P. F., & Larocca, L. M. (2010) · The Prostate · doi:10.1002/pros.21245 · Cited by 81 · see citing works
Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNα
Brender, C., Lovato, P., Sommer, V. H., Woetmann, A., Mathiesen, A.-M., Geisler, C., Wasik, M. A., & Ødum, N. (2004) · Leukemia · doi:10.1038/sj.leu.2403610 · Cited by 78 · see citing works
Smarter drugs emerging in pancreatic cancer therapy
Kleger, A., Perkhofer, L., & Seufferlein, T. T. W. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu013 · Cited by 77 · see citing works
Gao, J., Wang, L., Xu, J., Zheng, J., Man, X., Wu, H., Jin, J., Wang, K., Xiao, H., Li, S.-D., et al. (2013) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-32-86 · Cited by 72 · see citing works
Cloning and characterization of a functional promoter of the human SOCS-3 gene
He, B., You, L., Uematsu, K., Matsangou, M., Xu, Z., He, M., McCormick, F. P., & Jablons, D. M. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)03071-1 · Cited by 68 · see citing works
IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines
Block, K. M., Hanke, N. T., Maine, E. A., & Baker, A. F. (2012) · Pancreas · doi:10.1097/mpa.0b013e31823cdd10 · Cited by 62 · see citing works
Zhang, L., Li, J., Li, L., Zhang, J., Wang, X., Yang, C., Li, Y., Lan, F., & Lin, P. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu017 · Cited by 58 · see citing works
Self-citationKim, M., Kim, M.-S., Kim, W., Kang, M. A., Cacalano, N. A., Kang, S., Shin, Y.-J., & Jeong, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123133 · Cited by 57 · see citing works
Dhar, K., Rakesh, K., Pankajakshan, D., & Agrawal, D. K. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00570.2012 · Cited by 55 · see citing works
Wu, J., Xu, Y., Mo, D., Huang, P., Sun, R., Huang, L., Pan, S., & Xu, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093478 · Cited by 54 · see citing works
Self-citationGrowth impairment in IL-6-overexpressing transgenic mice is associated with induction of SOCS3 mRNA
Lieskovská, J., Guo, D., & Derman, E. (2003) · Growth Hormone & IGF Research · doi:10.1016/s1096-6374(02)00135-1 · Cited by 50 · see citing works
SOCS3 methylation in synergy with Reg3A overexpression promotes cell growth in pancreatic cancer
Wang, J., Zhou, H. W., Han, Y. K., Liu, X., Wang, M., Wang, X., Yin, G., Xu, L., & Xiang, M. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1184-8 · Cited by 46 · see citing works
Self-citationYang, X., Schaper, F., Teubner, A., Lammert, F., Heinrich, P. C., Matern, S., & Siewert, E. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.02.048 · Cited by 41 · see citing works
WAN, J., Che, Y., Kang, N., & Wu, W. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3368 · Cited by 36 · see citing works
Suppressor of Cytokine Signaling 3 Inhibits Breast Tumor Kinase Activation of STAT3*
Gao, Y.-W., Cimica, V., & Reich, N. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.334144 · Cited by 34 · see citing works
Expression of IL-6 receptor in pancreatic cancer: involvement in VEGF induction.
Masui, T., Hosotani, R., Doi, R., Miyamoto, Y., Tsuji, S., Nakajima, S., Kobayashi, H., Koizumi, M., Toyoda, E., Tulachan, S. S., et al. (2002) · PubMed · Cited by 33 · see citing works
Gene methylation and silencing of SOCS 3 in mantle cell lymphoma
Molavi, O., Wang, P., Zak, Z., Gélébart, P., Belch, A. R., & Lai, R. L. (2013) · British Journal of Haematology · doi:10.1111/bjh.12262 · Cited by 32 · see citing works
Lebel, E., Vallières, L., & Rivest, S. (2000) · Endocrinology · doi:10.1210/endo.141.10.7695 · Cited by 31 · see citing works
Activity of the Suppressor of Cytokine Signaling–3 Promoter in Human Non–Small-Cell Lung Cancer
He, B., You, L., Xu, Z., Mazières, J., Lee, A. Y., & Jablons, D. M. (2004) · Clinical Lung Cancer · doi:10.3816/clc.2004.n.015 · Cited by 29 · see citing works
Pro-malignant properties of STAT3 during chronic inflammation
Demaria, M., & Poli, V. (2012) · Oncotarget · doi:10.18632/oncotarget.482 · Cited by 24 · see citing works
SOCS‐3 antagonizes pro‐apoptotic effects of TRAIL and resveratrol in prostate cancer cells
Horndasch, M., & Čulig, Z. (2011) · The Prostate · doi:10.1002/pros.21353 · Cited by 23 · see citing works
Stofas, A., Levidou, G., Piperi, C., Adamopoulos, C., Dalagiorgou, G., Bamias, A., Karadimou, A., Lainakis, G. A., Papadoukakis, S., STRAVODIMOS, K. G., et al. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-149 · Cited by 23 · see citing works
Loss of Suppressors of Cytokine Signaling 3 Promotes Aggressiveness in Hepatocellular Carcinoma
Wu, W., Kim, H., Zhang, C., Meng, X.-L., & Wu, Z. (2014) · Journal of Investigative Surgery · doi:10.3109/08941939.2013.873098 · Cited by 16 · see citing works
Rengucci, C., Maio, G. D., Gardini, A. C., Zucca, M., Scarpi, E., Zingaretti, C., Foschi, G., Tumedei, M. M., Molinari, C., Saragoni, L., et al. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-014-0065-x · Cited by 15 · see citing works
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Mashouri, L., Yousefi, H., Aref, A., Ahadi, A., Molaei, F., & Alahari, S. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0991-5 · Cited by 1,345 · see citing works
Role of Matrix Metalloproteinases in Angiogenesis and Cancer
Quintero-Fabián, S., Arreola, R., Becerril‐Villanueva, E., Torres‐Romero, J. C., Arana‐Argáez, V. E., Lara‐Riegos, J., Ramírez-Camacho, M. A., & Álvarez-Sánchez, M. E. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01370 · Cited by 1,042 · see citing works
The ASD Living Biology: from cell proliferation to clinical phenotype
Courchesne, E., Pramparo, T., Gazestani, V. H., Lombardo, M. V., Pierce, K., & Lewis, N. E. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0056-y · Cited by 333 · see citing works
Inflammation-Induced Tumorigenesis and Metastasis
Hibino, S., Kawazoe, T., Kasahara, H., Itoh, S., Ishimoto, T., Sakata‐Yanagimoto, M., & Taniguchi, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115421 · Cited by 303 · see citing works
Wei, F., Ma, C., Zhou, T., Dong, X., Luo, Q., Geng, L., Ding, L., Zhang, Y., Zhang, L., Li, N., et al. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0694-8 · Cited by 245 · see citing works
DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy
Zhang, J., Yang, C., Wu, C., Cui, W., & Wang, L. (2020) · Cancers · doi:10.3390/cancers12082123 · Cited by 215 · see citing works
DNMT1: A key drug target in triple-negative breast cancer
Wong, K. K. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.05.010 · Cited by 197 · see citing works
Liu, B., Wu, S., Ma, J., Yan, S., Xiao, Z., Wan, L., Zhang, F., Shang, M., & Mao, A. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.09.026 · Cited by 165 · see citing works
Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature
Mohan, C. D., Rangappa, S., Preetham, H. D., Nayaka, S. C., Gupta, V. K., Basappa, B., Sethi, G., & Rangappa, K. S. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.03.016 · Cited by 158 · see citing works
Vainer, N., Dehlendorff, C., & Johansen, J. S. (2018) · Oncotarget · doi:10.18632/oncotarget.25661 · Cited by 153 · see citing works
TGF-β–induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis
Dees, C., Pötter, S., Zhang, Y., Bergmann, C., Zhou, X., Luber, M., Wohlfahrt, T., Karouzakis, E., Ramming, A., Gelse, K., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci122462 · Cited by 145 · see citing works
Valilou, S. F., Keshavarz‐Fathi, M., Silvestris, N., Argentiero, A., & Rezaei, N. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.01.007 · Cited by 141 · see citing works
Fu, Y., Liu, S., Zeng, S., & Shen, H. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0815-z · Cited by 138 · see citing works
DriverML: a machine learning algorithm for identifying driver genes in cancer sequencing studies
Han, Y., Yang, J., Qian, X., Cheng, W., Liu, S., Hua, X., Zhou, L., Yang, Y., Wu, Q., Liu, P., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz096 · Cited by 137 · see citing works
DNMT1 as a therapeutic target in pancreatic cancer: mechanisms and clinical implications
Wong, K. K. (2020) · Cellular Oncology · doi:10.1007/s13402-020-00526-4 · Cited by 132 · see citing works
Ruze, R., Song, J., Yin, X., Chen, Y., Xu, R., Wang, C., & Zhao, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01376-w · Cited by 103 · see citing works
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Burton, N. O., & Greer, E. L. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.08.006 · Cited by 85 · see citing works
Targeting epigenetic regulators for inflammation: Mechanisms and intervention therapy
Zhang, S., Meng, Y., Zhou, L., Qiu, L., Wang, H., Su, D., Zhang, B., Chan, K. M., & Han, J. (2022) · MedComm · doi:10.1002/mco2.173 · Cited by 82 · see citing works
IL-6 roles - Molecular pathway and clinical implication in pancreatic cancer - A systemic review.
Pop, V., Seicean, A., Lupan, I., Samașca, G., & Burz, C. (2017) · Immunology Letters · doi:10.1016/j.imlet.2016.11.010 · Cited by 76 · see citing works
DNA methylation and cancer: transcriptional regulation, prognostic, and therapeutic perspective
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Balakrishnan, A., Guruprasad, K. P., Satyamoorthy, K., & Joshi, M. B. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0079-7 · Cited by 66 · see citing works
Xiao, C., Hong, H., Yu, H., Yuan, J., Guo, C., Cao, H., & Li, W. (2018) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2018.1455208 · Cited by 62 · see citing works
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Hoffpauir, C. T., Bell, S. L., West, K. O., Jing, T., Wagner, A. R., Torres-Odio, S., Cox, J. S., West, A. P., Li, P., Patrick, K. L., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901511 · Cited by 55 · see citing works
Xu, Z., Ji, J., Xu, J., Li, D., Shi, G., Liu, F., Ding, L., Ren, J., Dou, H., Wang, T., et al. (2017) · FEBS Journal · doi:10.1111/febs.14133 · Cited by 54 · see citing works
Emerging roles of suppressor of cytokine signaling 3 in human cancers
Dai, L., Li, Z., Tao, Y., Liang, W., Hu, W., Zhou, S., Fu, X., & Wang, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112262 · Cited by 53 · see citing works
Self-citationAglan, H. A., Ahmed, H. H., El-Toumy, S. A. H., & Mahmoud, N. S. (2017) · Tumor Biology · doi:10.1177/1010428317699127 · Cited by 51 · see citing works
Xiang, S., Zou, P., Tang, Q., Zheng, F., Wu, J., Chen, Z., & Hann, S. S. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.12.001 · Cited by 52 · see citing works
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Li, L., Wu, J., Zheng, F., Tang, Q., Wu, W., & Hann, S. S. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0388-x · Cited by 48 · see citing works
Self-citationWu, J., Tang, Q., Yang, L., Chen, Y., Zheng, F., & Hann, S. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-00626-6 · Cited by 46 · see citing works
Self-citationFeng, Y. M., Guo, S., Zhao, Y., Dong, H., Qian, J., Hu, Y., Wu, L., Jia, Y., & Zhao, R. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01130-3 · Cited by 44 · see citing works
Chang, Y. C., Daza, R. A. M., Hevner, R. F., Costa, L. G., & Cole, T. B. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.01.013 · Cited by 45 · see citing works
Sun, Q., Shang, Y., Sun, F., Dong, X., Niu, J., & Li, F. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/8032187 · Cited by 42 · see citing works
Chen, Y., Tang, Q., Xiao, Q., Yang, L., & Hann, S. S. (2016) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12958 · Cited by 40 · see citing works
Self-citationWei, L., Huang, Y. C., Zhao, R., Zhang, J., Liu, Q., Liang, W., Ding, X., Gao, B., Li, B., Sun, C., et al. (2017) · Clinical and Experimental Medicine · doi:10.1007/s10238-017-0473-2 · Cited by 40 · see citing works
Francescangeli, F., Angelis, M. L. D., Baiocchi, M., Rossi, R., Biffoni, M., & Zeuner, A. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.592891 · Cited by 40 · see citing works
Wang, A., Yang, F., Tian, Y., Su, J.-H., Gu, Q., Chen, W., Gong, S.-X., Ma, X., Qin, X.-P., & Jiang, Z. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.656139 · Cited by 37 · see citing works
Huang, H., Chang, C., Wang, C., & Lin, K. (2021) · Cells · doi:10.3390/cells10010067 · Cited by 37 · see citing works
Cancer-Associated Fibroblast Diversity Shapes Tumor Metabolism in Pancreatic Cancer
Peiffer, R., Boumahd, Y., Gullo, C., Crake, R., Letellier, E., Bellahcène, A., & Peulen, O. (2022) · Cancers · doi:10.3390/cancers15010061 · Cited by 37 · see citing works
Kang, S., Kim, B. R., Kang, M. H., Kim, D. Y., Lee, D.-H., Oh, S. C., Min, B. W., & Um, J. W. (2018) · PLoS ONE · doi:10.1371/journal.pone.0205449 · Cited by 35 · see citing works
Christopher, A. F., Gupta, M., & Bansal, P. (2016) · Gene · doi:10.1016/j.gene.2016.08.044 · Cited by 35 · see citing works
Comprehensive analysis of regulation of DNA methyltransferase isoforms in human breast tumors
Hegde, M., & Joshi, M. B. (2021) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-021-03519-4 · Cited by 36 · see citing works
Dai, L., Tao, Y., Shi, Z., Liang, W., Hu, W., Xing, Z., Zhou, S., Guo, X., Fu, X., & Wang, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.881801 · Cited by 34 · see citing works
Self-citationExpression of miRNA-143 in Pancreatic Cancer and Its Clinical Significance
Xu, B., Liu, J., Xiang, X., Liu, S., Zhong, P., Xie, F., Mou, T., & Lai, L. (2018) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2018.2500 · Cited by 30 · see citing works
Epigenetic approach for angiostatic therapy: promising combinations for cancer treatment
Berndsen, R. H., Abdul, U. K., Weiss, A., Zoetemelk, M., Winkel, M. T. T., Dyson, P. J., Griffioen, A. W., & Nowak-Sliwinska, P. M. (2017) · Angiogenesis · doi:10.1007/s10456-017-9551-z · Cited by 29 · see citing works
Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives
Faldoni, F. L. C., Rainho, C. A., & Rogatto, S. R. (2020) · Cells · doi:10.3390/cells9051164 · Cited by 29 · see citing works
Dongoran, R. A., Wang, K., Lin, T., Yuan, T., & Liu, C. (2020) · Cancers · doi:10.3390/cancers12082084 · Cited by 28 · see citing works
Bansod, S., Dodhiawala, P. B., & Lim, K. (2021) · Cancers · doi:10.3390/cancers13215481 · Cited by 26 · see citing works
Carbotti, G., Nikpoor, A. R., Vacca, P., Gangemi, R. M. R., Giordano, C., Campelli, F., Ferrini, S., & Fabbi, M. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0608-z · Cited by 27 · see citing works
Soleimani, D., Miryan, M., Tutunchi, H., Navashenaq, J. G., Sadeghi, E., Ghayour‐Mobarhan, M., Ferns, G. A., & Ostadrahimi, A. (2020) · Phytotherapy Research · doi:10.1002/ptr.6856 · Cited by 26 · see citing works
NR1D1 suppressed the growth of ovarian cancer by abrogating the JAK/STAT3 signaling pathway
Wang, H., & Fu, Y. (2021) · BMC Cancer · doi:10.1186/s12885-021-08597-8 · Cited by 25 · see citing works
Dong, L., Ma, L., Ma, G. H., & Ren, H. (2019) · Scientific Reports · doi:10.1038/s41598-019-41616-0 · Cited by 25 · see citing works
Jing, W., Song, N., Liu, Y., Qu, X., Qi, Y., Li, C., Hou, K., Che, X., & Yang, X.-H. (2019) · Cancer Management and Research · doi:10.2147/cmar.s201610 · Cited by 24 · see citing works
Bulle, A. S., Dekervel, J., Libbrecht, L. J., Nittner, D., Deschuttere, L., Lambrecht, D., Cutsem, E. V., Verslype, C., & van Pelt, J. F. (2019) · Europe PMC (PubMed Central) · Cited by 24 · see citing works
Liu, F., Wang, Y., Cao, Y., Wu, Z., Ma, D., Cai, J., Sha, J., & Chen, Q. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110412 · Cited by 24 · see citing works
Gan, F., Zhou, X., Zhou, Y., Hou, L., Chen, X., Pan, C., & Huang, K. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02434-5 · Cited by 22 · see citing works
Liu, B., Yao, X., Zhang, C., Liu, Y., Li, W., Huang, Q., Wang, M., Zhang, Y., Hu, D., & Wu, W. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05590-w · Cited by 21 · see citing works
Srivastava, R. K., & Lodhi, N. (2022) · Biomolecules · doi:10.3390/biom12030417 · Cited by 19 · see citing works
Yang, S., Wang, B., Liu, C., Wang, Q., Wang, R., Su, W., Zhu, Y., Li, M., Guo, Z., Wu, X., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5620475 · Cited by 19 · see citing works
A zebrafish HCT116 xenograft model to predict anandamide outcomes on colorectal cancer
Maradonna, F., Fontana, C. M., Sella, F., Giommi, C., Facchinello, N., Rampazzo, C., Caichiolo, M., Hoseinifar, S. H., Valle, L. D., Doan, H. V., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05523-z · Cited by 18 · see citing works
Zhou, Z., Dong, Y., Li, N., Niu, M., Wang, S., Zhou, Y., Sun, Z., Chu, P., & Tang, Z. (2022) · Cell Biology International · doi:10.1002/cbin.11866 · Cited by 16 · see citing works
Expression and prognostic value of HER-2/neu, STAT3 and SOCS3 in hepatocellular carcinoma
Jiang, L.-H., Hao, Y.-L., & Zhu, J. (2018) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2018.09.011 · Cited by 16 · see citing works
Wang, R., Zhao, S., Chen, X., Xiao, Z., Wen, X., Zhong, X., Li, S., Cheng, H., & Huang, G. (2022) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-022-05307-5 · Cited by 14 · see citing works
Wei, L., Liu, Q., Huang, Y. C., Liu, Z., Zhao, R., Li, B., Zhang, J., Sun, C., Gao, B., Ding, X., et al. (2020) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2020.105685 · Cited by 14 · see citing works
Bazedoxifene as a novel strategy for treatment of pancreatic and gastric adenocarcinoma
Burkhardt, C., Bühler, L. H., Tihy, M., Morel, P., & Forni, M. (2019) · Oncotarget · doi:10.18632/oncotarget.26833 · Cited by 13 · see citing works
Feng, Q., Yu, Y.-Z., & Meng, Q. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10746 · Cited by 13 · see citing works
Khabipov, A., Freund, E., Liedtke, K. R., Käding, A., Riese, J., van der Linde, J., Kersting, S., Partecke, L.-I., & Bekeschus, S. (2021) · Cancers · doi:10.3390/cancers13112525 · Cited by 13 · see citing works
NRF2 and STAT3: friends or foes in carcinogenesis?
Arena, A., Romeo, M. A., Benedetti, R., Montani, M. S. G., Santarelli, R., Gonnella, R., D’Orazi, G., & Cirone, M. (2023) · Discover Oncology · doi:10.1007/s12672-023-00644-z · Cited by 12 · see citing works
Wright, G. M., Sonavane, M., & Gassman, N. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115475 · Cited by 11 · see citing works
Chu, P., Wang, S., Zhu, X., Yang, Y., Li, H., Tesfaldet, T., Shopit, A., Yang, Y., Ma, X., Peng, J., et al. (2020) · PubMed Central · Cited by 10 · see citing works
Fukui, H., Watari, J., Zhang, X., Ran, Y., Tomita, T., Oshima, T., Hirota, S., & Miwa, H. (2020) · Oncology Letters · doi:10.3892/ol.2020.11462 · Cited by 10 · see citing works
Zhao, X., Cao, D., Ren, Z., Liu, Z., Lv, S., Zhu, J.-Q., Li, L., Lang, R., & He, Q. (2020) · Bioscience Reports · doi:10.1042/bsr20200214 · Cited by 10 · see citing works
Du, Y., He, L., Ye, X., Chen, S., Li, G., Yu, Y., Ye, E., Huang, Y., Zhou, Y., Zhang, W., et al. (2022) · BioMed Research International · doi:10.1155/2022/3133096 · Cited by 9 · see citing works
Gough, M. E., Graviss, E. A., Chen, T. A., Obasi, E. M., & May, E. E. (2019) · Tuberculosis · doi:10.1016/j.tube.2019.04.010 · Cited by 8 · see citing works
Li, T., Liu, Q., Zhang, R., Liao, Q., & Zhao, Y. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01426-1 · Cited by 7 · see citing works
Niu, C., Wu, D., Li, A. J., Qin, K. H., Hu, D. A., Wang, E. J., Tucker, A. B., He, F., Huang, L., Wang, H., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-64413/v1 · Cited by 7 · see citing works
Self-citation(2022) · Biointerface Research in Applied Chemistry · doi:10.33263/briac131.018 · Cited by 4 · see citing works
Molecular Signature of Neuroinflammation Induced in Cytokine-Stimulated Human Cortical Spheroids
Kleijn, K. M. A. D., Straasheijm, K. R., Zuure, W. A., & Martens, G. J. M. (2022) · Biomedicines · doi:10.3390/biomedicines10051025 · Cited by 4 · see citing works
Jaganathan, S. S., Natarajan, U., & Rathinavelu, A. (2025) · Epigenomics · doi:10.1080/17501911.2025.2558497 · Cited by 1 · see citing works
Stromal Inflammation in Pancreatic Cancer: Mechanisms and Translational Applications
Boyle, K. A., James, M. A., Tsai, S., Evans, D. B., & Dwinell, M. B. (2017) · Springer eBooks · doi:10.1007/978-1-4939-6631-8_55-1 · Cited by 1 · see citing works
Stromal Inflammation in Pancreatic Cancer: Mechanisms and Translational Applications
Boyle, K. A., James, M. A., Tsai, S., Evans, D. B., & Dwinell, M. B. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7193-0_55 · Cited by 1 · see citing works
Chu, P., Wu, H., Chen, P., Wang, S.-M., Lin, H.-Y., Tang, F., & Chiang, E. I. (2022) · Research Square · doi:10.21203/rs.3.rs-1625349/v1
DNMT1 has prognostic values in HER2-positive breast cancerPreprint
Chu, P., Wu, H., Chen, P., Wang, S.-M., Lin, H.-Y., Tang, F., & Chiang, E. I. (2022) · Research Square · doi:10.21203/rs.3.rs-1929732/v1
Wang, R., Zhao, S., Chen, X., Xiao, Z., Wen, X., Zhong, X., Li, S., Cheng, H., & 黄官友 (2024) · Figshare · doi:10.6084/m9.figshare.26558603
Wang, R., Zhao, S., Chen, X., Xiao, Z., Wen, X., Zhong, X., Li, S., Cheng, H., & Huang, G. (2024) · Figshare · doi:10.6084/m9.figshare.26558606
- Authors
- Huang, L., Hu, B., Ni, J., Wu, J., Jiang, W., Chen, C., Yang, L., Zeng, Y., Wan, R., Hu, G., & Wang, X.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Hu, Guoyong
- Wang, Xingpeng
- ORCID
- Venue
- Journal of Experimental & Clinical Cancer Research
- Published
- 2016-02-04
- Volume
- 35
- Issue
- 1
- Pages
- 27-27
- ISSN
- 0392-9078 (ISSN-L)
- 1756-9966
- PMC
- PMC4743194
- OpenAlex
- W2299967230
- Cited by
- 86
- References
- 57
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 6 · 2022: 12 · 2021: 13 · 2020: 17 · 2019: 10 · 2018: 12 · 2017: 9 · 2016: 4
- FWCI
- 6.29
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2023-01-12)
- Open access
- gold
- doi.org
- Locations
- Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81372643, 81370568)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- SOCS3, IL-6/STAT3 signaling, DNMT1, DNA methylation, promoter hypermethylation, transcriptional repression, pancreatic cancer, tumor growth, metastasis, prognostic factors, decitabine, G1/S cell cycle arrest, cell migration and invasion, negative feedback regulation, retracted article, DNA methyltransferases
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, DNA (Cytosine-5-)-Methyltransferase 1, Animals, DNA (Cytosine-5-)-Methyltransferases, Female, Humans, Male, Neoplasm Metastasis, Neoplasm Transplantation, Pancreatic Neoplasms, Transcription, Genetic, Signal Transduction, Interleukin-6, Gene Expression Regulation, Neoplastic, DNA Methylation, Cell Line, Tumor, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice
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