Inhibition of CDH17 gene expression via RNA interference reduces proliferation and apoptosis of human MKN28 gastric cancer cells

Li,Rui; Yang,Hong‑Qiang; Xi,Hai‑Lin; Feng,Su; Qin,Rui‑Hao

doi:10.3892/ijo.2016.3783

Inhibition of CDH17 gene expression via RNA interference reduces proliferation and apoptosis of human MKN28 gastric cancer cells

Authors:
- Rui Li
- Hong‑Qiang Yang
- Hai‑Lin Xi
- Su Feng
- Rui‑Hao Qin
View Affiliations

Affiliations: Department of Central Laboratory, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, P.R. China, Department of General Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
Published online on: November 28, 2016 https://doi.org/10.3892/ijo.2016.3783
Pages: 15-22
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gastric cancer is the fourth most common type of cancer and the second cause of cancer‑related mortalities worldwide despite the use of multimodal therapy. Cadherins are transmembrane glycoproteins that are involved in tumorigenesis. CDH17 has been found to be over‑expressed in gastric cancer and its overexpression was associated with lymph node metastasis and tumor‑node‑metastasis stage of the patients, yet the exact role and molecular mechanism of CDH17 in gastric cancer have not been determined. Using a lentiviral system as a delivery mediator of RNA interference, we found that inhibition of CDH17 can lead to reduce proliferation and increase apoptosis of gastric cancer cell line MKN28 in vitro and significantly diminish their tumorigenicity in vivo. Our results of the present study suggest that CDH17 may be a promising candidate for the therapeutic targeting of gastric cancer.

View Figures

View References

1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
2	Sugano K: Screening of gastric cancer in Asia. Best Pract Res Clin Gastroenterol. 29:895–905. 2015. View Article : Google Scholar : PubMed/NCBI
3	Gessner R and Tauber R: Intestinal cell adhesion molecules. Liver-intestine cadherin. Ann N Y Acad Sci. 915:136–143. 2000. View Article : Google Scholar
4	Wendeler MW, Drenckhahn D, Gessner R and Baumgartner W: Intestinal LI-cadherin acts as a Ca²⁺-dependent adhesion switch. J Mol Biol. 370:220–230. 2007. View Article : Google Scholar : PubMed/NCBI
5	Ito R, Oue N, Yoshida K, Kunimitsu K, Nakayama H, Nakachi K and Yasui W: Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer. Virchows Archiv. 447:717–722. 2005. View Article : Google Scholar : PubMed/NCBI
6	Su MC, Yuan RH, Lin CY and Jeng YM: Cadherin-17 is a useful diagnostic marker for adenocarcinomas of the digestive system. Mod Pathol. 21:1379–1386. 2008. View Article : Google Scholar : PubMed/NCBI
7	Yu QF, Dong WG and Ren JL: Knockdown of Li-cadherin increases metastatic behaviors of LoVo cells. J Cancer Res Clin Oncol. 136:1641–1649. 2010. View Article : Google Scholar : PubMed/NCBI
8	Liu QS, Zhang J, Liu M and Dong WG: Lentiviral-mediated miRNA against liver-intestine cadherin suppresses tumor growth and invasiveness of human gastric cancer. Cancer Sci. 101:1807–1812. 2010. View Article : Google Scholar : PubMed/NCBI
9	Zhang J, Liu QS and Dong WG: Blockade of proliferation and migration of gastric cancer via targeting CDH17 with an artificial microRNA. Med Oncol. 28:494–501. 2011. View Article : Google Scholar
10	Hinoi T, Lucas PC, Kuick R, Hanash S, Cho KR and Fearon ER: CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithelium and intestinal metaplasia. Gastroenterology. 123:1565–1577. 2002. View Article : Google Scholar : PubMed/NCBI
11	Barros R, da Costa LT, Pinto-de-Sousa J, Duluc I, Freund JN, David L and Almeida R: CDX2 autoregulation in human intestinal metaplasia of the stomach: Impact on the stability of the phenotype. Gut. 60:290–298. 2011. View Article : Google Scholar :
12	Ge J and Chen Z, Wu S, Yuan W, Hu B and Chen Z: A clinicopathological study on the expression of cadherin-17 and caudal-related homeobox transcription factor (CDX2) in human gastric carcinoma. Clin Oncol (R Coll Radiol). 20:275–283. 2008. View Article : Google Scholar
13	Grötzinger C, Kneifel J, Patschan D, Schnoy N, Anagnostopoulos I, Faiss S, Tauber R, Wiedenmann B and Gessner R: LI-cadherin: A marker of gastric metaplasia and neoplasia. Gut. 49:73–81. 2001. View Article : Google Scholar : PubMed/NCBI
14	Ko S, Chu KM, Luk JM, Wong BW, Yuen ST, Leung SY and Wong J: CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach. J Pathol. 205:615–622. 2005. View Article : Google Scholar : PubMed/NCBI
15	Cui J, Chen Y, Chou WC, Sun L, Chen L, Suo J, Ni Z, Zhang M, Kong X, Hoffman LL, et al: An integrated transcriptomic and computational analysis for biomarker identification in gastric cancer. Nucleic Acids Res. 39:1197–1207. 2011. View Article : Google Scholar :
16	Correa P: Human gastric carcinogenesis: A multistep and multifactorial process - First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 52:6735–6740. 1992.PubMed/NCBI
17	Yasui W, Oue N, Sentani K, Sakamoto N and Motoshita J: Transcriptome dissection of gastric cancer: Identification of novel diagnostic and therapeutic targets from pathology specimens. Pathol Int. 59:121–136. 2009. View Article : Google Scholar : PubMed/NCBI
18	Ko S, Chu KM, Luk JM, Wong BW, Yuen ST, Leung SY and Wong J: Overexpression of LI-cadherin in gastric cancer is associated with lymph node metastasis. Biochem Biophys Res Commun. 319:562–568. 2004. View Article : Google Scholar : PubMed/NCBI
19	Wang J, Yu JC, Kang WM, Wang WZ, Liu YQ and Gu P: The predictive effect of cadherin-17 on lymph node micrometastasis in pN0 gastric cancer. Ann Surg Oncol. 19:1529–1534. 2012. View Article : Google Scholar
20	Xu Y, Zhang J, Liu QS and Dong WG: Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo. World J Gastroenterol. 18:3129–3137. 2012. View Article : Google Scholar PubMed/NCBI
21	Wu WK, Cho CH, Lee CW, Fan D, Wu K, Yu J and Sung JJ: Dysregulation of cellular signaling in gastric cancer. Cancer Lett. 295:144–153. 2010. View Article : Google Scholar : PubMed/NCBI
22	Song Y, Dong MM and Yang HF: Effects of RNA interference targeting four different genes on the growth and proliferation of nasopharyngeal carcinoma CNE-2Z cells. Cancer Gene Ther. 18:297–304. 2011. View Article : Google Scholar : PubMed/NCBI
23	Liu LX, Lee NP, Chan VW, Xue W, Zender L, Zhang C, Mao M, Dai H, Wang XL, Xu MZ, et al: Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma. Hepatology. 50:1453–1463. 2009. View Article : Google Scholar : PubMed/NCBI
24	Kwak JM, Min BW, Lee JH, Choi JS, Lee SI, Park SS, Kim J, Um JW, Kim SH and Moon HY: The prognostic significance of E-cadherin and liver intestine-cadherin expression in colorectal cancer. Dis Colon Rectum. 50:1873–1880. 2007. View Article : Google Scholar : PubMed/NCBI
25	Takamura M, Ichida T, Matsuda Y, Kobayashi M, Yamagiwa S, Genda T, Shioji K, Hashimoto S, Nomoto M, Hatakeyama K, et al: Reduced expression of liver-intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Lett. 212:253–259. 2004. View Article : Google Scholar : PubMed/NCBI
26	Tait SW and Green DR: Mitochondria and cell death: Outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 11:621–632. 2010. View Article : Google Scholar : PubMed/NCBI