{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA large body of work indicates that NDRG2 functions as a potent tumor‐suppressor molecule whose expression is frequently lost or reduced in a wide variety of human malignancies. In glioblastoma, meningioma, oral, esophageal, colorectal, renal and gallbladder cancers—and in several reviews summarizing its role—down‐regulation of NDRG2 (often via promoter hypermethylation or miRNA repression) correlates with aggressive tumor behavior, metastasis and poor patient prognosis. In many of these studies, forced expression of NDRG2 in tumor cells inhibited proliferation, invasion and metastasis, frequently through the modulation of cell–cycle regulators and by antagonizing oncogenic signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, NDRG2 is regulated by multiple upstream signals and acts as an important node in several signaling pathways. Studies have demonstrated that NDRG2 is an efficient substrate for SGK1 phosphorylation and that its expression is directly repressed by oncogenic Myc, while it can be induced by hypoxia‐responsive factor HIF‑1 as well as by nuclear receptors such as FXR. In addition, NDRG2 recruits protein phosphatase PP2A to dephosphorylate PTEN, thereby attenuating PI3K/AKT and even NF‑κB signaling in contexts such as adult T‑cell leukemia/lymphoma. Furthermore, structure–function analyses and investigations into its post‑transcriptional regulation (via microRNAs and promoter methylation) underscore a central role for NDRG2 in modulating cancer cell metabolism, cell cycle progression (via effects on AP‑1, cyclin D1, Skp2, p21 and p27) and resistance to radiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in oncogenesis, NDRG2 is deeply involved in regulating differentiation and the cellular stress response in normal tissues. Its expression is enriched in the brain, skeletal muscle and other differentiated tissues, where it participates in neuronal function and myogenesis, as well as in the regulation of astrocyte proliferation and morphology. Moreover, NDRG2 is implicated in diverse physiological processes ranging from estrogen‐mediated stabilization of Na⁺/K⁺‑ATPase to amelioration of liver fibrosis via modulation of TGF‑β signaling, and alterations in its phosphorylation status have been observed in neurodegenerative conditions such as Alzheimer’s disease and frontotemporal lobar degeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "39", "end_ref": "46"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yanchun Deng, Libo Yao, Ling Chau, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-05-0043"}], "href": "https://doi.org/10.1158/0008-5472.CAN-05-0043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16103061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16103061"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Na Liu, Lifeng Wang, Xinping Liu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Suppression of NF-kappaB activity by NDRG2 expression attenuates the invasive potential of highly malignant tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgp072"}], "href": "https://doi.org/10.1093/carcin/bgp072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19336468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19336468"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Soo-Kyung Shon, Aeyung Kim, Ji Young Kim, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Expression of NDRG2 in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1349-7006.2010.01529.x"}], "href": "https://doi.org/10.1111/j.1349-7006.2010.01529.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20331630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20331630"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Dake Chu, Zixi Zhang, Yunming Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prediction of colorectal cancer relapse and prognosis by tissue mRNA levels of NDRG2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-10-0614"}], "href": "https://doi.org/10.1158/1535-7163.MCT-10-0614"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21220491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21220491"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Anders Lorentzen, Rikke H Lewinsky, Jette Bornholdt, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-11-251"}], "href": "https://doi.org/10.1186/1471-2407-11-251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21676268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21676268"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Lei Gao, Guo-Jun Wu, Xue-Wu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of invasion and metastasis of prostate cancer cells by overexpression of NDRG2 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2011.06.015"}], "href": "https://doi.org/10.1016/j.canlet.2011.06.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21741166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21741166"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Ulrich Deuschle, Julia Schüler, Andreas Schulz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FXR controls the tumor suppressor NDRG2 and FXR agonists reduce liver tumor growth and metastasis in an orthotopic mouse xenograft model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0043044"}], "href": "https://doi.org/10.1371/journal.pone.0043044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23056173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23056173"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Myung-Jin Kim, Jihyun Lim, Young Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "N-myc downstream-regulated gene 2 (NDRG2) suppresses the epithelial-mesenchymal transition (EMT) in breast cancer cells via STAT3/Snail signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2014.06.023"}], "href": "https://doi.org/10.1016/j.canlet.2014.06.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25153349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25153349"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Dong Gwang Lee, Sang-Hyun Lee, Jang-Seong Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of NDRG2 promotes epithelial-mesenchymal transition of gallbladder carcinoma cells through MMP-19-mediated Slug expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2015.08.007"}], "href": "https://doi.org/10.1016/j.jhep.2015.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26292259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26292259"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Wei Hu, Chongxi Fan, Peng Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Emerging role of N-myc downstream-regulated gene 2 (NDRG2) in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6228"}], "href": "https://doi.org/10.18632/oncotarget.6228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26506239"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26506239"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Wei Hu, Yang Yang, Chongxi Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and pathological significance of N-Myc downstream-regulated gene 2 (NDRG2) in diverse human cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-016-1244-3"}], "href": "https://doi.org/10.1007/s10495-016-1244-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27113371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27113371"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Tomohiro Tamura, Tomonaga Ichikawa, Shingo Nakahata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of NDRG2 Expression Confers Oral Squamous Cell Carcinoma with Enhanced Metastatic Potential."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-16-2114"}], "href": "https://doi.org/10.1158/0008-5472.CAN-16-2114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28209617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28209617"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Yongzheng Ma, Lin Wu, Xuewu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KLF4 inhibits colorectal cancer cell proliferation dependent on NDRG2 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2017.5736"}], "href": "https://doi.org/10.3892/or.2017.5736"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28656310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28656310"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Liangliang Shen, Xuan Qu, Huichen Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDRG2 facilitates colorectal cancer differentiation through the regulation of Skp2-p21/p27 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-017-0118-7"}], "href": "https://doi.org/10.1038/s41388-017-0118-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29343851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29343851"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "James T Murray, David G Campbell, Nicholas Morrice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20041057"}], "href": "https://doi.org/10.1042/BJ20041057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15461589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15461589"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Jian Zhang, Fuyang Li, Xinping Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605820200"}], "href": "https://doi.org/10.1074/jbc.M605820200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17050536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17050536"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Yongjin Park, Soo-Kyung Shon, Aeyung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.08.195"}], "href": "https://doi.org/10.1016/j.bbrc.2007.08.195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17888401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17888401"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Junye Liu, Jing Zhang, Xiaowu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2010.02.028"}], "href": "https://doi.org/10.1016/j.yexcr.2010.02.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20206160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20206160"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jeremy H Herskowitz, Nicholas T Seyfried, Duc M Duong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphoproteomic analysis reveals site-specific changes in GFAP and NDRG2 phosphorylation in frontotemporal lobar degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/pr100666c"}], "href": "https://doi.org/10.1021/pr100666c"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20886841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20886841"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Jungwon Hwang, Yoonjeong Kim, Ho Bum Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the human N-Myc downstream-regulated gene 2 protein provides insight into its role as a tumor suppressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.170803"}], "href": "https://doi.org/10.1074/jbc.M110.170803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21247902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21247902"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Li Feng, Yun Xie, Hao Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of NDRG2 gene expression in human colorectal cancer involves promoter methylation and microRNA-650."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.02.081"}], "href": "https://doi.org/10.1016/j.bbrc.2011.02.081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21352815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21352815"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "I Van Sligtenhorst, Z-M Ding, Z-Z Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cardiomyopathy in α-kinase 3 (ALPK3)-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vet Pathol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0300985811402841"}], "href": "https://doi.org/10.1177/0300985811402841"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21441111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21441111"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Shingo Nakahata, Tomonaga Ichikawa, Phudit Maneesaay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms4393"}], "href": "https://doi.org/10.1038/ncomms4393"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24569712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24569712"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Tomonaga Ichikawa, Shingo Nakahata, Masahiro Fujii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of NDRG2 enhanced activation of the NF-κB pathway by PTEN and NIK phosphorylation for ATL and other cancer development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep12841"}], "href": "https://doi.org/10.1038/srep12841"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26269411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26269411"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Xinyuan Xu, Jianying Li, Xiang Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor suppressor NDRG2 inhibits glycolysis and glutaminolysis in colorectal cancer cells by repressing c-Myc expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4544"}], "href": "https://doi.org/10.18632/oncotarget.4544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26317652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26317652"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Y-J Guo, J-X Liu, Y-W Guan "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia induced upregulation of miR-301a/b contributes to increased cell autophagy and viability of prostate cancer cells by targeting NDRG2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2016)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26813459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26813459"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Xianghu Qu, Yun Zhai, Handong Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/a:1017934810825"}], "href": "https://doi.org/10.1023/a:1017934810825"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11936845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11936845"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Cathy Mitchelmore, Stine Büchmann-Møller, Lene Rask, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDRG2: a novel Alzheimer's disease associated protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2004.01.003"}], "href": "https://doi.org/10.1016/j.nbd.2004.01.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15207261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15207261"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Victoria C Foletta, Matthew J Prior, Nicole Stupka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDRG2, a novel regulator of myoblast proliferation, is regulated by anabolic and catabolic factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2008.167882"}], "href": "https://doi.org/10.1113/jphysiol.2008.167882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19204049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19204049"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Mario P Tschan, Deborah Shan, Judith Laedrach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDRG1/2 expression is inhibited in primary acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.leukres.2009.08.037"}], "href": "https://doi.org/10.1016/j.leukres.2009.08.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19775754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19775754"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Toshiaki Takeichi, Mika Takarada-Iemata, Koji Hashida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The effect of Ndrg2 expression on astroglial activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Int (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuint.2011.03.019"}], "href": "https://doi.org/10.1016/j.neuint.2011.03.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21672576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21672576"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Yan Li, Jiandong Yang, Shaoqing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "N-myc downstream-regulated gene 2, a novel estrogen-targeted gene, is involved in the regulation of Na+/K+-ATPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.247825"}], "href": "https://doi.org/10.1074/jbc.M111.247825"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21771789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21771789"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Jiandong Yang, Jin Zheng, Lin Wu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "NDRG2 is a novel p53-associated regulator of apoptosis in C6-originated astrocytes exposed to oxygen-glucose deprivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0057130"}], "href": "https://doi.org/10.1371/journal.pone.0057130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23451161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23451161"}]}]}]}