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Christopher J Sevinsky, Faiza Khan, Leila Kokabee, Anza Darehshouri, Krishna Rao Maddipati, Douglas S Conklin
BACKGROUND: Altered lipid metabolism is an emerging hallmark of aggressive breast cancers. The N-myc downstream regulated gene (NDRG1) gene plays a critical role in peripheral nervous system myelination, as inactivating mutations cause severe demyelinating neuropathy. In breast cancer, elevated NDRG1 expression has been linked to clinical outcomes, but its functional role in breast cancer physiology has remained unclear. METHODS: A meta-analysis of NDRG1 expression in multiple large publicly available genomic databases was conducted...
June 14, 2018: Breast Cancer Research: BCR
Soon-Chan Kim, Young-Kyoung Shin, Ye-Ah Kim, Sang-Geun Jang, Ja-Lok Ku
BACKGROUND: Resistance to preoperative radiotherapy is a major clinical problem in the treatment for locally advanced rectal cancer. The role of NDRG1 in resistance to ionizing radiation in rectal cancer has not been fully elucidated. This study aimed to investigate the effect of the reduced intracellular NDRG1 expression on radio-sensitivity of human rectal cancer cells for exploring novel approaches for treatment of rectal cancer. METHODS: Three radio-resistant human rectal cancer cell lines (SNU-61R80Gy, SNU-283R80Gy, and SNU-503R80Gy) were established from human rectal cancer cell lines (SNU-61, SNU-283, and SNU-503) using total 80 Gy of fractionated irradiation...
May 25, 2018: BMC Cancer
Wei Qi Hu, Wei Wang, Di Long Fang, Xue Feng Yin
BACKGROUND We screened the potential molecular targets and investigated the molecular mechanisms of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Microarray data of GSE47786, including the 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated as control cells samples, was downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; the protein-protein interaction (PPI) networks were constructed using STRING database and Cytoscape; the genetic alteration, neighboring genes networks, and survival analysis of hub genes were explored by cBio portal; and the expression of mRNA level of hub genes was obtained from the Oncomine databases...
May 24, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jun-Zhi Zhang, Zhan-Li Liu, Yao-Xian Zhang, Hai-Jiu Lin, Zhong-Jun Zhang
Background: Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4. Methods: A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ...
June 5, 2018: Chinese Medical Journal
Lang He, Kang Liu, Xiaoshan Wang, Hong Chen, Jin Zhou, Xun Wu, Tao Liu, Yongxue Yang, Xuemei Yang, Dandan Cui, Guiqin Song, Jianguo Lei, Jun Wang
BACKGROUND: Resistance to platinum-based chemotherapy becomes a major obstacle in lung cancer treatment. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism accounting for cisplatin-resistance. We aimed at identifying additional regulators in NER-mediated chemoresistance in a hypoxic setting induced by sodium glycididazole (CMNa)-sensitized cisplatin chemotherapy of non-small cell lung cancer (NSCLC). METHODS: We performed an RNA-sequencing (RNA-Seq) analysis to identify the genes whose expression had been differentially regulated in NER-deficient cells that had been treated by cisplatin/CMNa...
May 13, 2018: International Journal of Biochemistry & Cell Biology
Chun-Chi Chang, Ya-Sian Chang, Hsi-Yuan Huang, Kun-Tu Yeh, Ta-Chih Liu, Jan-Gowth Chang
Among women in Taiwan, thyroid cancer is the fifth most common malignant neoplasia. However, genomic profiling of papillary thyroid cancer (PTC) cases from Taiwan has not been attempted previously. We used whole-exome sequencing to identify mutations in a cohort of 19 PTC patients. Sequencing was performed using the Illumina system; Sanger sequencing was used to validate all identified mutations. We identified new somatic mutations in APC, DICER1, LRRC8D and NDRG1. We also found somatic mutations in ARID5A, CREB3L2, MDM4, PPP2R5A and TFPT; mutations in these genes had been found previously in other tumors, but had not been described previously in PTC...
May 9, 2018: Human Pathology
Kun-Chun Chiang, Shih-Wei Yang, Kai-Ping Chang, Tsui-Hsia Feng, Kang-Shuo Chang, Ke-Hung Tsui, Yi-Syuan Shin, Chiu-Chun Chen, Mei Chao, Horng-Heng Juang
Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N -myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion. CAPE treatment stimulated NDRG1 expression in NPC cells...
May 8, 2018: International Journal of Molecular Sciences
Lin Chen, Chao Xing, Guoyao Ma, Jing Luo, Wen Su, Meng Li, Qiumei Shi, Hongxuan He
The highly pathogenic avian influenza (HPAI) A/H5N1 virus hijacks host cellular machinery to complete its life cycle; identification of the host factors involved in viral replication may facilitate antiviral drug development. Here, we first characterize a metastasis suppressor, N-myc downstream-regulated gene 1 (NDRG1), and showed that it plays a crucial role in H5N1 viral replication. We found that H5N1 infection upregulated NDRG1 mRNA and protein expression. Overexpression of NDRG1 released approximately 4-fold more virions compared to the control group, whereas knockdown of NDRG1 resulted in a drop in viral RNA and protein production...
May 3, 2018: Virus Research
Bin Chen, Songtao Niu, Na Chen, Hua Pan, Xingao Wang, Zaiqiang Zhang
Charcot-Marie-Tooth disease 4D (CMT4D) is characterized by severe peripheral neuropathy and deafness. It is caused by mutations in the N-myc downstream-regulated gene 1 (NDRG1). We report a Chinese man with a homozygous mutation c.675C > T of NDRG1 that resulted in Q185X, representing the third known CMT4D patient of non-European ancestry. The patient presented with a 15-year-long history of progressive limb weakness accompanied by hearing loss and dysarthria. There was abnormal differentiation and increased interpeak latencies in brainstem auditory evoked potentials...
April 30, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Trefa Mohamad, Noor Kazim, Abhinav Adhikari, Judith K Davie
EGR1, one of the immediate-early response genes, can function as a tumor suppressor gene or as an oncogene in cancer. The function of EGR1 has not been fully characterized in rhabdomyosarcoma (RMS), a pediatric cancer derived from the muscle linage. We found that EGR1 is downregulated in the alveolar RMS (ARMS) subtype but expressed at levels comparable to normal skeletal muscle in embryonal RMS (ERMS). We found that overexpression of EGR1 in ARMS significantly decreased cell proliferation, mobility, and anchorage-independent growth while also promoting differentiation...
April 6, 2018: Oncotarget
Kyung Chan Park, Sharleen V Menezes, Danuta S Kalinowski, Sumit Sahni, Patric J Jansson, Zaklina Kovacevic, Des R Richardson
The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), exhibits pleiotropic activity, inhibiting metastasis of various tumor-types, while being correlated with metastasis in others. Notably, NDRG1 phosphorylation and cleavage are associated with its function, although it is unclear if these modifications occur universally, or selectively, in different cancer cell-types and if it contributes to its pleiotropy. Considering the suggested DNA repair role of nuclear NDRG1, the effects of the above post-translational modifications on its nuclear localization was examined...
August 2018: Biochimica et Biophysica Acta
Ji Won Byun, Hye Young An, Seung Dohn Yeom, Seok Jong Lee, Ho Yun Chung
The etiopathogenesis of infantile hemangioma has not been well understood, and it is accepted that angiogenic mediator dysregulation is the main contributor to the abnormal hemangioma capillary formation. The role of NDRG1, a hypoxia-inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR complex 2 pathway in infantile hemangioma have not been studied yet. The purpose of this study was to investigate NDRG1 and FOXO1 expression in the infantile hemangioma and the correlation of these proteins with proliferation and involution...
March 23, 2018: Experimental Dermatology
Hsin-Chen Lin, Ching-Ching Yeh, Lo-Yun Chao, Mong-Hsun Tsai, Hung-Hsin Chen, Eric Y Chuang, Liang-Chuan Lai
Hypoxia can lead to solid tumor aggressiveness by driving multiple signaling pathways. Long non-coding RNAs respond to several extrinsic stimuli, causing changes in cancer cells by participating in multiple steps of gene expression. However, genomic profiling of long non-coding RNAs regulated by oxygen in breast cancer remained unclear. Therefore, the aims of this study were to identify oxygen-responsive long non-coding RNAs in breast cancer cells, and to delineate their regulatory mechanisms. The expression profiling of long non-coding RNAs in breast cancer cells growing under normoxic, hypoxic, and re-oxygenated conditions was examined using next-generation sequencing technology...
February 13, 2018: Oncotarget
Hongsheng Wang, Wei Sun, Mengxiong Sun, Zeze Fu, Chenghao Zhou, Chongren Wang, Dongqing Zuo, Zifei Zhou, Gangyang Wang, Tao Zhang, Jing Xu, Jian Chen, Zhuoying Wang, Fei Yin, Zhenfeng Duan, Francis J Hornicek, Zhengdong Cai, Yingqi Hua
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. The abilities of chemotherapy resistance are major roadblock in the successful treatment of OS. The clarification of mechanism regarding cell survival during OS chemotherapy are important. Here, we examined HER4 expression by immunohistochemistry in a large series of OS tissues, and found HER4 expression correlated with tumor characteristics and patient survival rates. HER4 knockdown by shRNA inhibited OS cell growth and tumorigenesis, and induced cell senescence and apoptosis in vitro and in vivo...
May 2018: Biochimica et Biophysica Acta
Yun Yang, Youxun Liu, Rui Guo, Yun Fu, Ziheng Zhang, Pengfei Zhang, Pingxin Zhou, Tingting Wang, Tengfei Huang, Xiaotong Li, Changzheng Li
Dithiocarbamate has been tested for its effective anti-tumor activity, but the underlying mechanism remains unclear. We previously prepared a novel diththiocarbamate derivative, DpdtC with an ability of catalase inhibition. Here, we for the first time investigated the growth inhibition effects of DpdtC on HER2-amplified cancer cells and elucidated its mechanism of action. Results showed that DpdtC exerted the potent anti-tumor effects against HER2-overexpressed SK-OV-3 and SK-BR-3 cells, especially on SK-OV-3 cells with a higher NDRG1 level, which was also confirmed in the SK-OV-3 xenograft model...
February 21, 2018: Scientific Reports
Tomoko Dai, Yuichi Dai, Yoshihiko Murata, Ryan Edbert Husni, Noriyuki Nakano, Shingo Sakashita, Masayuki Noguchi
It has been reported that N-myc downstream regulated gene 1 (NDRG1) is related to the prognosis of non-small cell lung cancer (NSCLC), and associated with c-Myc degradation in NSCLC cell lines. However, the relationship of NDRG1 to prognosis or c-Myc expression in lung adenocarcinoma has not been well clarified. The present study was designed to investigate the prognostic significance of NDRG1 and/or c-Myc expression in lung adenocarcinoma using immunohistochemistry with a tissue microarray. We examined 184 lung adenocarcinomas and observed low expression of NDRG1 in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), whereas high expression of NDRG1 was seen in invasive adenocarcinoma...
April 2018: Pathology International
Y X He, Y Zhu, L J Yang, F Wang
No abstract text is available yet for this article.
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Céline Tiffon
OBJECTIVES: N-myc downstream-regulated gene-1 (NDRG1) is a hypoxia-inducible and differentiation-related protein and candidate biomarker in pancreatic cancer. As NDRG1 expression is lost in high-grade tumors, the effects of the differentiating histone deacetylase inhibitor trichostatin A (TSA) were examined in human pancreatic cancer cell lines representing different tumor grades. METHODS: PANC-1 (poorly differentiated) and Capan-1 (moderately to well-differentiated) cells were treated with TSA...
February 2018: Pancreas
Tong Lou, Chongdong Liu, Zhenyu Zhang
NDRG1 (N-myc downstream-regulated gene 1) was previously considered to be a differentiation-related gene. However, many other functions of NDRG1 have since been identified, including proliferation, migration, invasion, and vascularization of tumor cells. Currently regarded as a tumor suppressor in most studies, NDRG1 is abundant in prostate, brain, kidney, placental, and intestinal tissues. It is expressed in normal endometrium, with higher expression occurring in the secretory phase. NDRG1 was first identified as an inhibitor of signaling pathways associated with the pathology of endometriosis...
2017: Critical Reviews in Eukaryotic Gene Expression
Catherine McCaig, Paris Ataliotis, Anan Shtaya, Ayan S Omar, A Richard Green, Clive N Kind, Anthony C Pereira, Aniko Naray-Fejes-Toth, Geza Fejes-Toth, Rafael J Yáñez-Muñoz, James T Murray, Atticus H Hainsworth
Nitrones (e.g. α-phenyl-N-tert-butyl nitrone; PBN) are cerebroprotective in experimental stroke. Free radical trapping is their proposed mechanism. As PBN has low radical trapping potency, we tested Sgk1 induction as another possible mechanism. PBN was injected (100 mg/kg, i.p.) into adult male rats and mice. Sgk1 was quantified in cerebral tissue by microarray, quantitative RT-PCR and western analyses. Sgk1+/+ and Sgk1-/- mice were randomized to receive PBN or saline immediately following transient (60 min) occlusion of the middle cerebral artery...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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