Small interfering RNA‑mediated knockdown of Twist attenuates the aggressive phenotypes of human endometrial carcinoma Ishikawa cells

Pan,Yilian; Liu,Xiaoyi; Huang,Yong

doi:10.3892/etm.2017.5214

Small interfering RNA‑mediated knockdown of Twist attenuates the aggressive phenotypes of human endometrial carcinoma Ishikawa cells

Authors:
- Yilian Pan
- Xiaoyi Liu
- Yong Huang
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Affiliations: Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, Shanghai 200030, P.R. China
Published online on: September 27, 2017 https://doi.org/10.3892/etm.2017.5214
Pages: 5647-5651

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Abstract

The present study aimed to determine the effect of Twist downregulation on the proliferation, apoptosis and migration of human endometrial carcinoma Ishikawa cells. Endogenous expression of the Twist transcription factor was knocked down by delivery of Twist‑targeting small interfering RNA (siRNA). Changes in the expression of epithelial‑mesenchymal transition biomarkers, namely epithelial (E)‑cadherin, neural (N)‑cadherin and Twist, were determined by western blot analysis. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell proliferation and migration were analyzed using cell‑counting and wound‑healing assays, respectively. Transfection with Twist siRNA led to a significant reduction in the expression of Twist and N‑cadherin (P<0.05), while significantly increasing the expression of E‑cadherin, relative to negative control transfectants (all P<0.05). Proliferation was also significantly decreased in Ishikawa cells transfected with Twist siRNA (P<0.05), which was accompanied by an increased rate of apoptosis and cell cycle arrest at S‑phase. In addition, Twist downregulation led to a significant reduction in cell migration (P<0.05). These data suggest that Twist serves a role in the regulation of cell proliferation and migration in Ishikawa cells and may represent a potential target for the treatment of human endometrial carcinoma.

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1	Jemal A, Thomas A, Murray T and Thun M: Cancer statistics, 2002. CA Cancer J Clin. 52:23–47. 2002. View Article : Google Scholar : PubMed/NCBI
2	Lotocki RJ, Copeland LJ, DePetrillo AD and Muirhead W: Stage I endometrial adenocarcinoma:Treatment results in 835 patients. Am J Obstet Gynecol. 146:141–144. 1983. View Article : Google Scholar : PubMed/NCBI
3	Tsai JH and Yang J: Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 27:2192–2206. 2013. View Article : Google Scholar : PubMed/NCBI
4	Wijnhoven BP, Dinjens WN and Pignatelli M: E-cadherin-catenin cell-cell adhesion complex and human cancer. Br J Surg. 87:992–1005. 2000. View Article : Google Scholar : PubMed/NCBI
5	Bremnes RM, Veve R, Gabrielson E, Hirsch FR, Baron A, Bemis L, Gemmill RM, Drabkin HA and Franklin WA: High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non–small-cell lung cancer. J Clin Oncol. 20:2417–2428. 2000. View Article : Google Scholar
6	Cheng L, Nagabhushan M, Pretlow TP, Pretlow TP, Amini SB and Pretlow TG: Expression of E-cadherin in primary and metastatic prostate cancer. Am J Pathol. 148:1375–1380. 1996.PubMed/NCBI
7	Sakuragi N1, Nishiya M, Ikeda K, Ohkouch T, Furth EE, Hareyama H, Satoh C and Fujimoto S: Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol. 53:183–189. 1994. View Article : Google Scholar : PubMed/NCBI
8	Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A and Weinberg RA: Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 117:927–939. 2004. View Article : Google Scholar : PubMed/NCBI
9	Vernon AE and LaBonne C: Tumor metastasis: A new Twist on epithelial-mesenchymal transitions. Curr Biol. 14:R719–R721. 2004. View Article : Google Scholar : PubMed/NCBI
10	Puisieux A, Valsesia-Wittmann S and Ansieau S: A twist for survival and cancer progression. Br J Cancer. 94:13–17. 2006. View Article : Google Scholar : PubMed/NCBI
11	Deng JJ, Zhang W, Xu XM, Zhang F, Tao WP, Ye JJ and Ge W: Twist mediates an aggressive phenotype in human colorectal cancer cells. Int J Oncol. 48:1117–1124. 2016. View Article : Google Scholar : PubMed/NCBI
12	Yang J, Hou Y, Zhou M, Wen S, Zhou J, Xu L, Tang X, Du YE, Hu P and Liu M: Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network. Int J Biochem Cell Biol. 71:62–71. 2016. View Article : Google Scholar : PubMed/NCBI
13	Fan Q, Qiu MT, Zhu Z, Zhou JH, Chen L, Zhou Y, Gu W, Wang LH, Li ZN, Xu Y, et al: Twist induces epithelial-mesenchymal transition in cervical carcinogenesis by regulating the TGF-β/Smad3 signaling pathway. Oncol Rep. 34:1787–1794. 2015. View Article : Google Scholar : PubMed/NCBI
14	Kwok WK, Ling MT, Lee TW, Lau TC, Zhou C, Zhang X, Chua CW, Chan KW, Chan FL, Glackin C, et al: Up-regulation of Twist in prostate cancer and its implication as a therapeutic target. Cancer Res. 65:5153–5162. 2005. View Article : Google Scholar : PubMed/NCBI
15	Lee TK, Poon RT, Yuen AP, Ling MT, Kwok WK, Wang XH, Wong YC, Guan XY, Man K, Chau KL, et al: Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res. 12:5369–5376. 2006. View Article : Google Scholar : PubMed/NCBI
16	Tang H, Massi D, Hemmings BA, Mandalà M, Hu Z, Wicki A and Xue G: AKT-ions with a TWIST between EMT and MET. Oncotarget. 7:62767–62777. 2016. View Article : Google Scholar : PubMed/NCBI
17	Lai YJ, Lin CI, Wang CL and Chao JI: Expression of survivin and p53 modulates honokiol-induced apoptosis in colorectal cancer cells. J Cell Biochem. 115:1888–1899. 2014.PubMed/NCBI
18	Lee SM, Kwon JI, Choi YH, Eom HS and Chi GY: Induction of G2/M arrest and apoptosis by water extract of Strychni Semen in human gastric carcinoma AGS cells. Phytother Res. 22:752–758. 2008. View Article : Google Scholar : PubMed/NCBI
19	Yunlan L, Juan Z and Qingshan L: Antitumor activity of Di-n-Butyl(2,6-difluorobenzo-hydroxamato) tin (IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis. PLoS One. 9:e907932014. View Article : Google Scholar : PubMed/NCBI
20	Maestro R, Dei Tos AP, Hamamori Y, Krasnokutsky S, Sartorelli V, Kedes L, Doglioni C, Beach DH and Hannon GJ: Twist is a potential oncogene that inhibits apoptosis. Genes. 13:2207–2217. 1999. View Article : Google Scholar
21	Van Doorn R, Dijkman R, Vermeer MH, Out-Luiting JJ, vander Raaij-Helmer EM, Willemze R and Tensen CP: Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sézary syndrome identified by gene expression analysis. Cancer Res. 64:5578–5586. 2004. View Article : Google Scholar : PubMed/NCBI
22	Vichalkovski A, Gresko E, Hess D, Restuccia DF and Hemmings BA: PKB/AKTphosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage. Oncogene. 29:3554–3565. 2010. View Article : Google Scholar : PubMed/NCBI
23	Horikawa T, Yang J, Kondo S, Yoshizaki T, Joab I, Furukawa M and Pagano JS: Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma. Cancer Res. 67:1970–1978. 2007. View Article : Google Scholar : PubMed/NCBI
24	Cheng GZ, Chan J, Wang Q, Zhang W, Sun CD and Wang LH: Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res. 67:1979–1987. 2007. View Article : Google Scholar : PubMed/NCBI