title: EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression.
abstract: Early growth response 1 (EGR1) is a multifunctional transcription factor; Positive and negative functions of EGR1 in various tumors rely on the integrated functions of various genes it regulates. In this study, we observed the role of EGR1 in non-small-cell lung carcinoma (NSCLC) and identified genes that influence cell fate and tumor development. Various assays showed that EGR1 arrested cell mobility, inhibited migration, and induced apoptosis. Microarray analysis revealed that 100 genes, including CDKN1C, CDC27 and PRKDC, changed their mRNA expressions with the increase of EGR1 and contributed to intervention of tumor progression. Bioinformatics analysis and promoter analysis indicated that an EGR1 binding site was situated in the promoter of KRT18 (also named CK18) and KRT18 could assist in inhibition of NSCLC development. The expression level of EGR1 and KRT18 in NSCLC clinical cases was investigated by immunohistochemistry, in which the protein expression of KRT18 was found to be significantly associated with EGR1 and lymph node metastasis. The results collectively confirm that EGR1 functions as a tumor suppressor in NSCLC. This study is the first to report KRT18 expression is directly regulated by EGR1, and contributes to decrease malignancy of NSCLC.
authors.affiliation: Institute of Biomedicine & Department of Cell Biology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, China.
authors.forename: Huihua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Biomedicine & Department of Cell Biology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Cancer Center of Guangzhou Medical University, GuangZhou, China.
authors.forename: Jiakang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Biomedicine & Department of Cell Biology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Guang
authors.affiliation: Institute of Biomedicine & Department of Cell Biology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Institute of Biomedicine & Department of Cell Biology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Biomedicine & Department of Cell Biology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Tan
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, GuangZhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051766:Early Growth Response Protein 1; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053538:Keratin-18 / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C488421:KRT18 protein, human; D053538:Keratin-18