Downregulation of YAP inhibits proliferation and induces apoptosis in Eca‑109 cells

Cui,Mu; Li,Zhen

doi:10.3892/etm.2017.5492

Downregulation of YAP inhibits proliferation and induces apoptosis in Eca‑109 cells

Authors:
- Mu Cui
- Zhen Li
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Affiliations: School of Nursing, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China
Published online on: November 10, 2017 https://doi.org/10.3892/etm.2017.5492
Pages: 1048-1052

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Abstract

A previous study reported that Yes‑associated protein (YAP) gene was overexpressed in esophageal squamous cell carcinoma (ESCC); however, the exact role of YAP in ESCC remains largely unclear. The present study aimed to investigate the effects of YAP inhibition on ESCC. In order to investigate the exact role of YAP in ESCC cells, a stable YAP low‑expression ESCC cell line was established using YAP‑small interfering RNA. MTT assay was performed to examine the cell proliferation ability, while flow cytometry were used to detect the cell apoptosis and cell cycle distribution. In addition, reverse transcription‑quantitative polymerase chain reaction and western blot analysis were applied for mRNA and protein level detection, respectively. The results suggested that YAP gene inhibition significantly repressed the ECA‑109 cell proliferation and induced cell apoptosis, whereas this inhibition had no significant effects on cell cycle. Furthermore, the expression levels of cell apoptosis‑associated proteins were determined in the current study, and the data demonstrated that the B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein ratio and phosphorylated extracellular signal‑regulated kinase expression were significantly reduced, while the p53 and caspase 3 levels were notably increased in YAP gene‑inhibited ECA‑109 cells. In conclusion, the current study revealed that YAP gene inhibition suppresses the proliferation and induces apoptosis in ECA‑109 cells, indicating that the YAP gene serves as an oncogene in ESCC.

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1	Kranzfelder M, Büchler P and Friess H: Surgery within multimodal therapy concepts for esophageal squamous cell carcinoma (ESCC): The MRI approach and review of the literature. Adv Med Sci. 54:158–169. 2009. View Article : Google Scholar : PubMed/NCBI
2	Chen ZL, Zhao XH, Wang JW, Li BZ, Wang Z, Sun J, Tan FW, Ding DP, Xu XH, Zhou F, et al: microRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin. J Biol Chem. 286:10725–10734. 2011. View Article : Google Scholar : PubMed/NCBI
3	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
4	Ma S, Bao JYJ, Kwan PS, Chan YP, Tong CM, Fu L, Zhang N, Tong AHY, Qin YR, Tsao SW, et al: Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma. Gastroenterology. 143:675–686.e12. 2012. View Article : Google Scholar : PubMed/NCBI
5	Chen W, He Y, Zheng R, Zhang S, Zeng H, Zou X and He J: Esophageal cancer incidence and mortality in China, 2009. J Thorac Dis. 5:19–26. 2013.PubMed/NCBI
6	Lagergren J and Lagergren P: Oesophageal cancer. BMJ. 341:c62802010. View Article : Google Scholar : PubMed/NCBI
7	Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F and Capocaccia R; EUROCARE Working Group, : EUROCARE-4. Survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J Cancer. 45:931–991. 2009. View Article : Google Scholar : PubMed/NCBI
8	Liu AM, Xu Z and Luk JM: An update on targeting Hippo-YAP signaling in liver cancer. Expert Opin Ther Targets. 16:243–247. 2012. View Article : Google Scholar : PubMed/NCBI
9	Hong L, Cai Y, Jiang M, Zhou D and Chen L: The Hippo signaling pathway in liver regeneration and tumorigenesis. Acta Biochim Biophys Sin (Shanghai). 47:46–52. 2015. View Article : Google Scholar : PubMed/NCBI
10	Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, Deng CX, Brugge JS and Haber DA: Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci USA. 103:pp. 12405–12410. 2006; View Article : Google Scholar : PubMed/NCBI
11	Wang X, Su L and Ou Q: Yes-associated protein promotes tumor development in luminal epithelial derived breast cancer. Eur J Cancer. 48:1227–1234. 2012. View Article : Google Scholar : PubMed/NCBI
12	Ge L, Smail M, Meng W, Shyr Y, Ye F, Fa KH, Li X, Zhou HM and Bhowmick NA: Yes-associated protein expression in head and neck squamous cell carcinoma nodal metastasis. PLoS One. 6:e275292011. View Article : Google Scholar : PubMed/NCBI
13	Cui ZL, Han FF, Peng XH, Chen X, Luan CY, Han RC, Xu WG and Guo XJ: Yes-associated protein 1 promotes adenocarcinoma growth and metastasis through activation of the receptor tyrosine kinase Axl. Int J Immunopathol Pharmacol. 25:989–1001. 2012. View Article : Google Scholar : PubMed/NCBI
14	Avruch J, Zhou D and Bardeesy N: YAP oncogene overexpression supercharges colon cancer proliferation. Cell Cycle. 11:1090–1096. 2012. View Article : Google Scholar : PubMed/NCBI
15	Wang J, Ma L, Weng W, Qiao Y, Zhang Y, He J, Wang H, Xiao W, Li L, Chu Q, et al: Mutual interaction between YAP and CREB promotes tumorigenesis in liver cancer. Hepatology. 58:1011–1020. 2013. View Article : Google Scholar : PubMed/NCBI
16	Muramatsu T, Imoto I, Matsui T, Kozaki K, Haruki S, Sudol M, Shimada Y, Tsuda H, Kawano T and Inazawa J: YAP is a candidate oncogene for esophageal squamous cell carcinoma. Carcinogenesis. 32:389–398. 2011. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Liu AM, Wong KF, Jiang X, Qiao Y and Luk JM: Regulators of mammalian Hippo pathway in cancer. Biochim Biophys Acta. 1826:357–364. 2012.PubMed/NCBI
19	Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, et al: Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell. 125:1253–1267. 2006. View Article : Google Scholar : PubMed/NCBI
20	Steinhardt AA, Gayyed MF, Klein AP, Dong J, Maitra A, Pan D, Montgomery EA and Anders RA: Expression of Yes-associated protein in common solid tumors. Hum Pathol. 39:1582–1589. 2008. View Article : Google Scholar : PubMed/NCBI
21	Xu MZ, Yao TJ, Lee NP, Ng IO, Chan YT, Zender L, Lowe SW, Poon RT and Luk JM: Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer. 115:4576–4585. 2009. View Article : Google Scholar : PubMed/NCBI
22	Wang Y, Dong Q, Zhang Q, Li Z, Wang E and Qiu X: Overexpression of yes-associated protein contributes to progression and poor prognosis of non-small-cell lung cancer. Cancer Sci. 101:1279–1285. 2010. View Article : Google Scholar : PubMed/NCBI
23	Dubreuil G, Magliano M, Dubrana MP, Lozano J, Lecomte P, Favery B, Abad P and Rosso MN: Tobacco rattle virus mediates gene silencing in a plant parasitic root-knot nematode. J Exp Bot. 60:4041–4050. 2009. View Article : Google Scholar : PubMed/NCBI
24	Li JC, Yang XR, Sun HX, Xu Y, Zhou J, Qiu SJ, Ke AW, Cui YH, Wang ZJ, Wang WM, et al: Up-regulation of Krüppel-like factor 8 promotes tumor invasion and indicates poor prognosis for hepatocellular carcinoma. Gastroenterology. 139:2146–2157. 2010. View Article : Google Scholar : PubMed/NCBI
25	Tsujimoto Y and Shimizu S: Bcl-2 family: Life-or-death switch. FEBS Lett. 466:6–10. 2000. View Article : Google Scholar : PubMed/NCBI
26	Dhillon AS, Hagan S, Rath O and Kolch W: MAP kinase signalling pathways in cancer. Oncogene. 26:3279–3290. 2007. View Article : Google Scholar : PubMed/NCBI
27	Surget S, Khoury MP and Bourdon JC: Uncovering the role of p53 splice variants in human malignancy: A clinical perspective. Onco Targets Ther. 7:57–68. 2013.PubMed/NCBI