Effects of KLF17 on growth of xenograft tumor in nude mice and scree-ning and functional analysis of KLF17-regulated target genes in vivo
10.3969/j.issn.1000-4718.2018.05.003
- VernacularTitle:KLF17 对裸鼠移植瘤生长的影响及其在体调控靶基因的筛选和功能分析
- Author:
Xing-Dong CAI
1
;
Wen-Jia LAI
;
Ying YANG
;
Miao ZHANG
;
Yuan-Shun HUANG
;
Hong-Ming MA
Author Information
1. 暨南大学附属第一医院呼吸内科
- Keywords:
Krüppel-like factor 17;
Lung adenocarcinoma;
Nude mice;
Xenograft tumor;
Gene regulation
- From:
Chinese Journal of Pathophysiology
2018;34(5):785-792
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the role of Krüppel-like factor 17(KLF17)in nude mouse xenograft model, and to explore the target genes regulated by KLF 17, the target gene functions and the signaling pathways involved.ME-THODS:The KLF17 was stably up-regulated in human lung adenocarcinoma A 549 cells and down-regulated in human lung adenocarcinoma H322 cells by lentiviral infection.BLAB/c nu/nu nude mice(n=11)were divided into KLF17 up-regual-tion group(n=5)and KLF17 down-regulation group(n=6).The right and left bodies of the nude mice were subcutane-ously injected with KLF17-up-/down-regulating cells and the counterpart empty vectors were used as control cells,respec-tively.The effects of KLF17 on the growth of the cell-derived xenografts in nude mice were analyzed.The mRNA and pro-tein expression levels of KLF17 in xenograft tumor tissues were analyzed by real-time PCR and immunohistochemical stai-ning,respectively.Transcriptome sequencing was used to explore the differentially expressed genes in the xenograft tumors derived from KLF17-up-regulating A549 cells,and the functions of the potential target genes were analyzed using the lung adenocarcinoma data from The Cancer Genome Atlas(TCGA)database.Gene Ontology and KEGG PATHWAY enrichment analyses were performed to analyze the functions of the differentially expressed genes and the involved signal pathways.RE-SULTS:The growth rate of KLF17-up-regulating A549 cell-derived xenograft tumors in the nude mice was significantly lower than that in empty control group(P<0.05),while the growth rate and the weight of KLF 17-down-regulating H322 cell-derived xenograft tumors in nude mice were significantly higher than those in empty control group(P<0.01 and P<0.05,respectively).In the A549 cell-derived xenograft tumor model,the KLF17 mRNA and protein were significantly in-creased in KLF17 up-regualtion group.The transcriptome sequencing showed the potential target genes regulated by KLF 17 were ras homolog family member V(RHOV)and coronin 1C(CORO1C).Ten-year cumulative survival time of the patients with lung adenocarcinoma from TCGA database was significantly different between high and low expression of RHOV and CORO1C at mRNA level.Increased expression levels of RHOV and CORO1C were correlated with short survival time in the patients with lung adnocarcinoma.The results of Gene Ontology and KEGG PATHWAY enrichment analyses indicated that the target genes(differentially expressed genes)regulated by KLF17 were related to the stimulation response,growth and adhesion of tumor cells,and participated in chemotaxis-,adhesion-and extracellular matrix receptor-related signaling path-ways.CONCLUSION:KLF17 inhibits the xenograft tumor growth in nude mice,and inhibits the oncogenes such as RHOV and CORO1C.The target genes regulated by KLF17 participate in the regulation of tumor adhesion-and growth-related sig-naling pathways.
