N-myc downstream-regulated gene 2 promotes proliferation of HO-8910 ovarian cancer cells

Objective To investigate N-myc downstream-regulated gene 2(NDRG2) expression in ovarian cancer cells and its potential usefulness as a diagnostic marker and/or target for therapeutic intervention.Methods Human NDRG2 L/S gene was obtained by revers-transcription polymerase chain reaction(RT-PCR). Sequence analysis confirmed the identity of NDRG2 L/S gene, which was then inserted into a eukaryotic vector p LNCX2, which was in turn transfected into NDRG2 gene-negative HO-8910 cells. Flow cytometry(FCM) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay were conducted to determine the proliferation rate of HO-8910 cells. Cisplatin resistance of HO-8910 cells transfected with p LNCX2-NDRG2 L/S was evaluated by FCM. Tumors were generated in female nude mice by subcutaneous injection of HO-8910 cells.Results NDRG2 gene was isolated and its expression vector was successfully constructed. NDRG2 expression positively correlated with the proliferation of HO-8910 cells. NDRG2 L/S promoted tumorigenicity in HO-8910 cells.Conclusion The present study identified a novel function of NDRG2 L/S gene and demonstrated its involvement in the promotion of ovarian cancer cell proliferation and enhancement of cisplatin resistance in HO-8910 cells. Future studies are warranted to determine the relationship between NDRG2 upregulation and ovarian cancer progression.

N-myc下游调节基因1-NDRG1

N-myc下游调节基因1 （N-myc downstream regulated gene 1,NDRG1）属于NDRG家族,α/β水解酶超家族,但无水解酶催化位点.研究表明[1],该基因与细胞生长发育[2]、肿瘤细胞生长和转移均有关,同时还参与了应激反应[3]、脂类的生物合成、髓鞘的形成以及组织的缺氧过程等;可被多种分化调节剂诱导表达,譬如在诱导分化剂维甲酸、巴豆油、佛波酯等的作用下,NDRG1 mRNA及蛋白表达上调[4].因而对该基因的深入研究,可进一步阐明肿瘤诱导分化治疗的分子生物学机制.

Expression and Biological Function of N-myc Down-regulated Gene 1 in Human Cervical Cancer

The expression of N-myc down-regulated gene 1 (NDRG1) has previously been reported to be involved in the proliferation,differentiation,invasion and metastasis of cancer cells,but its role in cervical cancer is still unclear.This study aimed to investigate the expression of NDRG1gene in human cervical cancer and its effect on aggressive tumor behaviors.The NDRG1 expression in cervical tissues and cells was detected by RT-PCR.Specific expression plasmid pEGFP-N1-NDRG1-GFP was used to enhance the expression of NDRG1 in human cervical cancer cell lines.The mRNA and protein level of NDRG1 was assessed by RT-PCR and Western blotting,respectively.Its effects on cell proliferation,migration,invasion,cell cycle and apoptosis were detected by MTT,transwell migration assay and flow cytometry (FCM),respectively.The results showed that the expression of NDRG1 in cervical cancer tissues and cells was significantly lower than in normal cervical tissues (P【0.001).After transfection with pEGFP-N1-NDRG1-GFP,the mRNA and protein expression of NDRG1 was up-regulated in Siha cells,which suppressed cell proliferation (P【0.001),induced cell cycle arrest (P【0.05),reduced invasion and migration of Siha cells (P【0.05),but caused no cell apoptosis.Moreover,vascular endothelial growth factor (VEGF),a tumor-induced angiogenesis factor,was markedly reduced and E-cadherin,a cell adhesion molecule,was increased in the cells transfected with pEGFP-N1-NDRG1-GFP.It was concluded that up-regulated NDRG1 may play a role in the suppression of malignant cell growth,invasion and metastasis of human cervical cancer.

N-myc downstream regulated gene 1 inhibition of tumor progression in Caco2 cells

BACKGROUND Invasion and migration are the irreversible stages of colorectal cancer(CRC).The key is to find a sensitive,reliable molecular marker that can predict the migration of CRC at an early stage.N-myc downstream regulated gene 1(NDRG1)is a multifunctional gene that has been tentatively reported to have a strong relationship with tumor invasion and migration,however the current molecular role of NDRG1 in CRC remains unknown.AIM To explore the role of NDRG1 in the development of CRC.METHODS NDRG1 stably over-expressed Caco2 cell line was established by lentiviral infection and NDRG1 knock-out Caco2 cell line was established by CRISPR/Cas9.Furthermore,the mRNA and protein levels of NDRG1 in Caco2 cells after NDRG1 over-expression and knockout were detected by real-time polymerase chain reaction and western blot.The cell proliferation rate was measured by the cell counting kit-8 method;cell cycle and apoptosis were detected by flow cytometry;invasion and migration ability were detected by the 24-transwell method.RESULTS NDRG1 over-expression inhibited Caco2 proliferation and the cell cycle could be arrested at the G1/S phase when NDRG1 was over-expressed,while the number of cells in the G2 phase was significantly increased when NDRG1 was knocked out.This suggests that NDRG1 inhibited the proliferation of Caco2 cells by arresting the cell cycle in the G1/S phase.Our data also demonstrated that NDRG1 promotes early cell apoptosis.Invasion and migration of cells were extensively inhibited when NDRG1 was over-expressed.CONCLUSION NDRG1 inhibits tumor progression in Caco2 cells which may represent a potential novel therapeutic strategy for the treatment of CRC.

Inhibition of N-Myc down regulated gene 1 in in vitro cultured human glioblastoma cells

AIM: To study short ds RNA oligonucleotides(si RNA)as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1(NDRG1) gene induced under different physiological conditions(Normoxia and hypoxia) modulating NDRG1 transcription, m RNA stability and translation. METHODS: A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 × 107 cells, nuclear extracts were prepared according to previous protocols. The p SUPERNDRG1 vectors were designed, two sequences were selected from the human NDRG1 c DNA(5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on β-actin and hypoxia-inducible factor(HIF)-1α m RNA sequences in Gen Bank. NDRG1 m RNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia(P < 0.05 was considered significant).RESULTS: si RNA- and iodoacetate(IAA)-mediated downregulation of NDRG1 m RNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results. CONCLUSION: NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it canrepresent a potential target for tumor treatment in human glioblastoma. The si RNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays.

Regulation of HIF-1 α to Expression of N-myc Downstream Regulated Gene 1 in Colorectal Carcinoma

Plasmid expressing small interfering RNA （siRNA） against HIF-1α （pSilence-2.1-U6-siRNA） was constructed and transfected into LS174T cells in hypoxia condition.After expression of siRNA against HIF-1 α in LS174T cells, expressions of HIF-1 α and N-myc downstream regulated gene 1 （NDRG1） gene were inhibited significantly. HIF-1 cta transcripts were positive in 67.7% （42/62） and 44.4% （8/18） of colorectal adenocarcinoma and adenoma, re- spectively. The mean percentage of cells with positive hybridization of HIF-1 α mRNA increases with the development from Duke stage A to stage C＋D （p〈 0.05）. The positive staining rate of NDRG1 protein was significant higher in than that in colorectal adenoma colorectal adenocarcinoma group group （p〈 0.05）. The level of HIF-1 a transcripts was positively correlated with the level of NDRG1 protein （p 〈 0.05） during colorectal tumor progression. HIF-1α and its down stream gene NDRG1 may play roles in tumor progression of human colorectal carcinoma.

NDRG-1基因甲基化与乳腺癌发生的关系

目的对NDRG-1基因启动子区甲基化状态进行研究,探讨NDRG-1基因甲基化在乳腺癌发生中的作用。方法采用双色荧光杂交微阵列基因芯片技术对33例乳腺癌样本和癌旁组织样本进行NDRG-1基因启动子区甲基化状态研究。结果33例肿瘤样本和癌旁组织样本中NDRG-1基因启动子区CpG位点均有不同程度的甲基化,肿瘤组织中NDRG-1基因启动子区CpG位点甲基化率显著高于相应的癌旁样本组织(t=14.12,P<0.05)。结论DNA甲基化作为NDRG-1基因的重要调控机制,NDRG-1基因启动子区过甲基化可能在乳腺癌的发生过程中起重要作用。

分化相关基因NDRG1在消化系统肿瘤中的研究进展

N-myc下游调节基因1（N-myc downstream regulated gene 1,NDRG1）是近年来发现的一种分化相关基因,多种生理或病理因素的刺激可诱导NDRG1的表达,但其确切的生物学功能尚不完全清楚。

乳腺癌中NDRG-1基因甲基化状态研究

目的研究NDRG1基因启动子区甲基化状态,探讨NDRG-1基因甲基化在乳腺癌发生中的作用。方法采用双色荧光杂交微阵列基因芯片技术对33对乳腺癌标本和癌旁组织标本NDRG-1基因启动子区甲基化状态进行研究。结果肿瘤标本和癌旁组织标本中NDRG-1基因启动子区CpG位点均有不同程度的甲基化,肿瘤组织中NDRG-1基因启动子区CpG位点甲基化率明显高于相应的癌旁组织(t=14.12,P<0.05)。结论NDRG-1基因启动子区过甲基化可能在乳腺癌的发生过程中起重要作用。

肾细胞癌NDRG-1和E-cadherin表达及其与临床病理因素、MVD及预后的关系

目的:研究N-myc下游调节基因(NDRG-1)和上皮型钙粘素(E-cadherin)在肾细胞癌组织中的表达,探讨其与肾细胞癌临床病理因素、微血管密度(MVD)及预后的关系。方法:应用免疫组织化学SP法检测49例肾细胞癌组织及相对应的癌旁肾脏组织中NDRG-1、E-cadherin表达情况。结果:NDRG-1和E-cadherin在正常肾组织表达均高于肾细胞癌组织,差异有显著性(P<0.01);二者随肾细胞癌肿瘤组织学分级、临床分期增高表达减弱,有肾门淋巴结转移者表达低于无淋巴结转移者,E-cadherin表达降低还与肾盂浸润、肾静脉癌栓相关,差异均有显著性(P<0.05);NDRG-1和E-cadherin表达均与肾细胞癌MVD呈负相关性(P<0.05);NDRG-1和E-cadherin表达阴性病例术后存活时间均显著短于阳性病例(P=0.001);肾细胞癌组织中NDRG-1和E-cadherin表达无相关性(r=-0.253,P=0.086)。结论:NDRG-1和E-cadherin表达降低与肾细胞癌的浸润、转移及血管生成和生存时间密切相关,检测NDRG-1和E-cadherin可作为预测肾细胞癌浸润转移及预后有意义的指标。

N-myc下游调控基因1在肝细胞癌中的表达及其与预后的相关性

目的肝细胞癌(HCC)是肝最常见的原发性恶性肿瘤之一。N-myc下游调控基因1(NDRG1)在肝癌中的作用尚存争议。文章旨在证实NDRG1在HCC患者中的表达及其预后价值、潜在的生物学功能以及对免疫系统的影响。方法选择TCGA数据库中的肝癌数据,包括58例正常肝组织标本和407例肝癌标本及与之相应的临床资料,对NDRG1基因在正常肝组织和肝癌组织中的表达进行分析。使用GTEx数据库显示NDRG1在人类肝组织中的表达。利用HPA分析NDRG1蛋白在HCC的表达情况。根据NDRG1表达的中位数,将所有患者分为NDRG1低表达组和NDRG1高表达组,并分析2组的生存情况。分析NDRG1表达与组织学分级(G)、临床S分期、临床T分期相关性。通过GSEA富集分析KEGG通路,探讨NDRG1的生物学功能。使用TIMER和CIBERSORT来分析HCC中NDRG1与免疫浸润细胞的相关性。结果与正常肝组织相比,肝癌组织中NDRG1表达增加(P<0.001)。NDRG1表达与组织学分级(G)(P<0.001)、临床S分期(P=0.03)、临床T分期(P=0.018)呈正相关。NDRG1的高表达与较差的总生存率显著相关(P=0.005)。单因素Cox分析分析显示NDRG1高表达与较差的总生存率显著相关(P<0.001)。多因素Cox分析分析表明,高NDRG1表达是独立危险因素,与肝细胞癌患者的总生存期密切相关(P<0.001)。通过GSEA分析,发现NDRG1可能通过DNA修复、E 2 F、MYC-V 1、G 2 M检查点、P53通路、TGF-β通路等途径调控肿瘤的发生发展。TIMER和CIBERSORT分析显示NDRG1的高表达与M 0巨噬细胞呈正相关。结论NDRG1在肝癌组织中高表达,提示预后不佳。可能通过肿瘤免疫浸润细胞改变肿瘤微环境促进肝癌的发生发展。NDRG1可作为HCC预后的生物学标志物。

N-myc下游调节基因1与肿瘤发生、发展及转移的关系

恶性肿瘤是危害人类健康最严重的一类疾病。目前，临床研究领域主要集中在肿瘤的早期发现和寻找新的有效的治疗手段。新的肿瘤标记物的发现可以为恶性肿瘤的诊断和治疗提供很大的帮助。N-myc下游调节基因1（NDRG1）是新近发现的与细胞分化有关的基因，能够被多种生理或病理因素刺激诱导表达。尽管其确切功能仍不十分清楚，但是它在恶性肿瘤中的异常表达引起许多学者的兴趣和关注，对它的研究也不断增多。本文就NDRG1与肿瘤的相关研究进展作一综述。

microRNA-1290通过NDRG1/NF-κB/IL-6信号通路促进结肠癌细胞迁移和侵袭

目的:探讨微小RNA-1290(microRNA-1290,miR-1290)通过N-myc下游调节基因1(N-Myc downstream-regulated gene 1,NDRG1)调控NF-κB/IL-6活化分子机制及其对结肠癌细胞侵袭和迁移的影响。方法:选择48例结肠癌患者肿瘤及癌旁组织,用免疫组织化学染色检测IL-6表达;qRT-PCR法检测20例肿瘤组织,结肠癌细胞与正常结肠上皮HCoEpiC细胞中IL-6 mRNA及miR-1290表达;结合miR-1290类似物及抑制剂处理,蛋白质印迹和ELISA法分别检测结肠癌细胞中p-NF-κB、NF-κB、NDRG1、上皮钙黏素、波形蛋白表达以及IL-6外泌量;小干扰RNA及中和性抗体靶向下调IL-6表达,miR-1290类似物处理,划痕实验以及Transwell实验检测结肠癌细胞迁移、侵袭能力。结果:结肠癌中IL-6免疫组织化学染色评分明显高于癌旁组织(P<0.01);结肠癌瘤体内miR-1290与IL-6 mRNA表达呈正相关(r=0.8454,P<0.01);与HCoEpiC细胞相比,结肠癌细胞中miR-1290表达明显增高(P均<0.01);上调miR-1290表达可抑制NDRG1表达从而促进NF-κB信号通路及上皮间充质转化活化(P<0.01),而下调miR-1290表达可促进NDRG1、上皮钙黏素表达并抑制p-NF-κB和波形蛋白形成(P<0.01);划痕实验显示上调miR-1290表达可增强结肠癌细胞迁移能力,而敲低IL-6后细胞愈合率则明显抑制(P<0.01);miR-1290类似物处理促进结肠癌细胞侵袭,而抗体中和IL-6可显著降低侵袭细胞数(P<0.01)。结论:结肠癌细胞中miR-1290可通过抑制NDRG1形成促进NF-κB/IL-6调控轴诱导的细胞迁移和侵袭发生。

N-myc下游调控基因1在呼吸系统疾病中的研究进展

N-myc下游调控基因1(N-myc downstream regulated gene-1,NDRG1)是NDRG家族的第一个成员,与低氧和应激相关。NDRG1广泛分布在全身多种组织器官中,具有特有的分子结构和化学修饰。在肺中NDRG1主要表达在呼吸道组织内,其表达水平和化学修饰与多种呼吸系统疾病的发生发展有密切关系,包括感染性疾病、慢性气道炎性疾病、低氧相关疾病(如肺损伤、急性呼吸窘迫综合征)等,同时在肿瘤低氧微环境、肿瘤进展及耐药等方面也发挥重要作用。本文就NDRG1在呼吸系统疾病中的相关研究进展作一综述。

乳腺癌中NDRG-1基因甲基化及其体外逆转研究

目的:探讨N-myc下游调节基因(N-myc downstream regulated gene-1,NDRG-1)基因在乳腺癌组织中的甲基化状态,研究甲基化酶抑制剂5-氮杂-2'-脱氧胞苷(5-Aza-2'-deoxycytidine,5-Aza-CdR)对乳腺癌细胞株T47D的生长增殖及NDRG-1mRNA表达的影响。方法:采用甲基化特异性PCR(methylation specific PCR,MSP)法检测乳腺癌组织、相应癌旁组织和乳腺良性病变组织中NDRG-1基因启动子甲基化状态;5-Aza-CdR处理T47D细胞后,MTT法观察细胞生长活性的变化,RT-PCR法检测处理前后抑癌基因NDRG-1的mRNA表达变化。结果:NDRG-1基因在乳腺癌组织中甲基化率为46.8%,癌旁组织中甲基化率为21.3%,而乳腺良性病变组织均未检测到甲基化。T47D细胞经5-Aza-CdR处理后,与对照组相比,细胞生长受到明显抑制。RT-PCR检测发现,与对照组相比,不同浓度处理组细胞的NDRG-1mRNA表达增多。结论:NDRG-1基因甲基化状态与乳腺癌发生有密切关系。5-Aza-CdR逆转T47D细胞NDRG-1基因甲基化,恢复该基因的表达,从而抑制肿瘤细胞生长。

核受体NR6A1与NDRG1互作促进肝癌进展

核受体在细胞稳态的维持以及疾病的发生发展等方面发挥着重要的作用。为了探究核受体亚家族6A组成员1(nuclear receptor subfamily 6 group A member 1,NR6A1)在肝癌中的作用及机制,首先,分析了癌症基因组图谱(The Cancer Genome Atlas,TCGA)等数据库信息,发现NR6A1在肝癌中异常高表达且与患者预后不良有关;然后,通过CCK-8(Cell Counting Kit-8)、5-乙炔基-2′-脱氧尿苷(5-ethynyl-2′-deoxyuridine,EdU)、划痕实验发现,干扰NR6A1使肝癌细胞的增殖明显受到抑制但不影响细胞的迁移;其次,通过免疫共沉淀、免疫荧光、RNA干扰和过表达等实验,鉴定出N-myc下游调控基因1(N-myc downstream-regulated gene 1,NDRG1)是NR6A1在肝癌中的互作蛋白质,二者在肝癌中的表达呈正相关,且NR6A1正调控NDRG1的表达;最后,利用功能拯救实验证实,干扰NDRG1可以抑制NR6A1过表达造成的肝癌细胞增殖增强的现象。综上可知,NR6A1通过与NDRG1相互结合且上调NDRG1的表达来发挥促癌作用。

NDRG-1、WWOX及P53基因在胃癌组织中的表达及临床意义

目的探讨肿瘤相关基因NDRG-1(N-myc downst reamrelated gene1)、WWOX(WW domain-con-taining oxidoreductase)及P53在胃癌组织中的表达情况及其与临床、病理因素之间的关系.方法用免疫组织化学染色的方法分别检测NDRG-1、WWOX及P53基因在31例胃癌组织及15例正常胃粘膜组织中的表达情况.结果WWOX、NDRG-1基因在胃癌组织中的表达明显降低,与正常组织比较差异有统计学意义(P<0.05).且二者均与肿瘤的侵润深度、淋巴结转移情况密切相关(P<0.05).WWOX与癌组织的分化程度密切相关(P<0.05),而NDRG-1与癌组织的分化程度无关(P>0.05).P53(突变型)基因在胃癌组织中的表达明显高于正常组织,二者比较差异有统计学意义(P<0.05),其表达与癌组织的分化程度、侵润深度、淋巴结转移情况密切相关(P<0.05).以上3种基因的表达情况均与患者的年龄、性别无关(P>0.05).WWOX与NDRG-1基因在胃癌组织中的表达呈正相关(r=0.561,P=0.001);而二者与P53基因的表达均呈负相关(WWOX与P53组:r=-0.411,P=0.022;NDRG-1与P53组:r=-0.360,P=0.047).结论WWOX、NDRG-1、P53(野生型)基因同为抑癌基因,且三者之间在胃癌的发生、发展及转移过程中有着明显的协同作用.因此,联合评价其功能具有更重要的临床意义.

卵巢癌组织中LSD1、NDRG1基因表达量与癌细胞迁移、侵袭的相关性研究

目的:研究卵巢癌组织中赖氨酸特异性组蛋白去甲基化酶1(lysine-specific demethylase 1,LSD1)、N-myc下游调节基因1(N-myc downstream regulated 1,NDRG1)基因表达量与癌细胞迁移、侵袭的相关性。方法:选择2014年3月~2017年7月扶风县人民医院接受手术切除的卵巢癌患者作为研究对象,手术切除后取卵巢癌组织和癌旁组织,测定LSD1、NDRG1基因及迁移基因、侵袭基因的表达量。结果:卵巢癌组织中LSD1、YKL40、COX2、Twist、IFITM1、CatL、CTHRC1、MMP2、FUNDC1基因的mRNA表达量显著高于癌旁组织,NDRG1、E-cadherin、Wnt5a基因的mRNA表达量显著低于癌旁组织;LSD1高表达的卵巢癌组织中YKL40、COX2、Twist、IFITM1、CatL、CTHRC1、MMP2、FUNDC1的mRNA表达量显著高于LSD1低表达的卵巢癌组织,E-cadherin、Wnt5a基因的mRNA表达量显著低于LSD1低表达的卵巢癌组织。结论:卵巢癌组织中LSD1高表达、NDRG1低表达能够促进癌细胞的迁移、侵袭。

The delivery of N-myc downstream-regulated gene 2(NDRG2)self-amplifying mRNA via modified lipid nanoparticles as a potential treatment for drug-resistant and metastatic cancers

The protein,N-myc downstream-regulated gene 2(NDRG2),a tumor suppressor,is significantly decreased or absent in many types of cancer.There is a significant negative correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion,in different cancers.In contrast,the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation,growth,adhesion and migration of many types of cancer cells.The in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer cells.We hypothesize that the delivery of the mRNA of the NDRG2 protein,encapsulated by lipid nanoparticles,could represent a potential treatment of metastatic and drug-resistant cancers.This would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase,obtained from an in vitrotranscribed(IVT)mRNA.The IVT mRNA would be encapsulated in a lipid nanoformulation.The efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive,nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells,would be treated with the nanoformulation and monitored for efficacy and adverse effects.If the appropriate preclinical studies indicate this formulation is efficacious and safe,it is possible it could be evaluated in clinical trials.

Lipoxin A4 Ameliorates Lipopolysaccharide-lnduced A549 Cell Injury through Upregulation of N-myc Downstream-Regulated Gene-1

Background： Lipoxin A4 （LXA4） can alleviate lipopolysaccharide （LPS）-induced acute lung injury （ALl） 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. Candidate genes affected by LXA4 were explored by transcriptome sequencing ofA549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis ofA549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor （ALX） inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase （PI3K） inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression. Results： The A549 cell models of ALl were constrticted and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream- regulated gent- 1 （NDRG 1 ） was validated by real-time-PCR and Western blot. NDRG 1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG 1 expression induced by LXA4. NDRG I siRNA suppressed viability of LPS-treated A549 cells （treatment vs. control, 0.605± 0.063 vs. 0.878 ± 0.083, P = 0.040） and ENaC-α expression （treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008）. LY294002 inhibited NDRG 1 （treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P 0.001 ） and ENaC-α （treatment vs. control, 0.236 ± 0.021 vs. 0.814 ±0.025, P 〈 0.001 ） expressions and serum- and glucocorticoid-inducible kinase I phosphorylation （treatment vs. control, 0.442± 0.024 vs. 1.046 ± 0.082, P = 0.002）, indicating the PI3K signaling pathway was involved in regulating NDRG 1 expression induced by LXA4. Conclusion： Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.