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YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.

Zhang J, Wen X, Ren XY, Li YQ, Tang XR, Wang YQ, He QM, Yang XJ, Sun Y, Liu N, Ma J - J. Exp. Clin. Cancer Res. (2016)

Bottom Line: Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT.Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo.The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, People's Republic of China.

ABSTRACT

Background: Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored.

Methods: We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting.

Results: YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

Conclusions: YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment.

No MeSH data available.


Related in: MedlinePlus

YPEL3 mRNA and protein expression levels in NPC cell lines and tissues. a-b Quantitative RT-PCR (a) and western blotting analysis (b) of YPEL3 expression levels in NPC cell lines. c Quantitative RT-PCR analysis of YPEL3 mRNA expression levels in NPC (n = 12) and normal nasopharyngeal epithelial tissues (n = 12); d western blotting analysis of YPEL3 protein levels in NPC (T, n = 4) and normal nasopharyngeal epithelial tissues (N, n = 4). All of the experiments were performed at least three times. Data presented are the mean ± SD; the P-value was calculated using the Student t-test
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Fig1: YPEL3 mRNA and protein expression levels in NPC cell lines and tissues. a-b Quantitative RT-PCR (a) and western blotting analysis (b) of YPEL3 expression levels in NPC cell lines. c Quantitative RT-PCR analysis of YPEL3 mRNA expression levels in NPC (n = 12) and normal nasopharyngeal epithelial tissues (n = 12); d western blotting analysis of YPEL3 protein levels in NPC (T, n = 4) and normal nasopharyngeal epithelial tissues (N, n = 4). All of the experiments were performed at least three times. Data presented are the mean ± SD; the P-value was calculated using the Student t-test

Mentions: The mRNA and protein expression levels of YPEL3 in the normal nasopharyngeal epithelial NP69 cell line and seven NPC cell lines were assessed by quantitative RT-PCR and western blotting. Compared to NP69 cells, YPEL3 was significantly downregulated in the NPC cell lines at both mRNA and protein level (Fig. 1a, b). We also investigated the YPEL3 mRNA levels in 12 frozen NPC tissues and 12 normal nasopharyngeal epithelial tissues, and observed that YPEL3 mRNA was expressed at considerably lower levels in the NPC tissues (Fig. 1c). Western blotting validated the decreased YPEL3 protein levels in the NPC tissues (Fig. 1d). These results indicate that decreased YPEL3 expression may promote NPC development and progression.Fig. 1


YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.

Zhang J, Wen X, Ren XY, Li YQ, Tang XR, Wang YQ, He QM, Yang XJ, Sun Y, Liu N, Ma J - J. Exp. Clin. Cancer Res. (2016)

YPEL3 mRNA and protein expression levels in NPC cell lines and tissues. a-b Quantitative RT-PCR (a) and western blotting analysis (b) of YPEL3 expression levels in NPC cell lines. c Quantitative RT-PCR analysis of YPEL3 mRNA expression levels in NPC (n = 12) and normal nasopharyngeal epithelial tissues (n = 12); d western blotting analysis of YPEL3 protein levels in NPC (T, n = 4) and normal nasopharyngeal epithelial tissues (N, n = 4). All of the experiments were performed at least three times. Data presented are the mean ± SD; the P-value was calculated using the Student t-test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940860&req=5

Fig1: YPEL3 mRNA and protein expression levels in NPC cell lines and tissues. a-b Quantitative RT-PCR (a) and western blotting analysis (b) of YPEL3 expression levels in NPC cell lines. c Quantitative RT-PCR analysis of YPEL3 mRNA expression levels in NPC (n = 12) and normal nasopharyngeal epithelial tissues (n = 12); d western blotting analysis of YPEL3 protein levels in NPC (T, n = 4) and normal nasopharyngeal epithelial tissues (N, n = 4). All of the experiments were performed at least three times. Data presented are the mean ± SD; the P-value was calculated using the Student t-test
Mentions: The mRNA and protein expression levels of YPEL3 in the normal nasopharyngeal epithelial NP69 cell line and seven NPC cell lines were assessed by quantitative RT-PCR and western blotting. Compared to NP69 cells, YPEL3 was significantly downregulated in the NPC cell lines at both mRNA and protein level (Fig. 1a, b). We also investigated the YPEL3 mRNA levels in 12 frozen NPC tissues and 12 normal nasopharyngeal epithelial tissues, and observed that YPEL3 mRNA was expressed at considerably lower levels in the NPC tissues (Fig. 1c). Western blotting validated the decreased YPEL3 protein levels in the NPC tissues (Fig. 1d). These results indicate that decreased YPEL3 expression may promote NPC development and progression.Fig. 1

Bottom Line: Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT.Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo.The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, People's Republic of China.

ABSTRACT

Background: Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored.

Methods: We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting.

Results: YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

Conclusions: YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment.

No MeSH data available.


Related in: MedlinePlus