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Upregulation of long noncoding RNA CCAT1-L promotes epithelial–mesenchymal transition in gastric adenocarcinoma

Authors Fang H, Liu HM, Wu WH, Liu H, Pan Y, Li WJ

Received 9 April 2018

Accepted for publication 7 June 2018

Published 10 September 2018 Volume 2018:11 Pages 5647—5655

DOI https://doi.org/10.2147/OTT.S170553

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Hua Fang,1,* Hui-Min Liu,2,* Wei-Hua Wu,3 Han Liu,1 Yong Pan,1 Wen-Jun Li4

1Department of Oncology, Fuxing Hospital, Capital Medical University, Beijing 100038, China; 2Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China; 3Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 100038, China; 4Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China

*These authors contributed equally to this work

Objective: In this study, we aimed to investigate the role of a long-chain noncoding RNA, colorectal cancer-associated transcript 1-long (CCAT1-L) in gastric adenocarcinoma.
Patients and methods: Expressions of CCAT1-L and c-MYC mRNA and MYC protein in gastric adenocarcinoma tissue and adjacent normal tissues of 60 patients were analyzed using quantitative real-time polymerase chain reaction and Western blot, respectively. The CCAT1-L levels in the normal gastric epithelial cell line, GES1, and human gastric adenocarcinoma cell lines, MGC803, MKN-28, SGC7901, and BGC823 were analyzed by quantitative real-time polymerase chain reaction. CCAT1-L knockdown in MGC803 and MKN28 cells was performed using RNA interference, followed by evaluating cell proliferation, invasion, and migration with soft agar colony formation assay, scratch wound assay, and transwell assay. Twenty BALB/C-nu-nu nude mice were inoculated with gastric tumor xenografts and treated with CCAT1-L small-interfering RNA (siRNA), followed by monitoring survival and tumor growth. Western blot was also used to analyze the expression of epithelial–mesenchymal transition-related proteins, including MYC, RAS, T-ERK, P-ERK, E-cadherin, and vimentin, in gastric adenocarcinoma MKN-28 cells.
Results: The expression of CCAT1-L and MYC in tumor tissue was significantly higher than that in adjacent normal tissues (P<0.001). There was a positive correlation between the expression level of CCAT1-L mRNA and c-MYC mRNA (r=0.863, P<0.001). CCAT1-L expression was also significantly higher in gastric adenocarcinoma cell lines than that in normal cell lines (P<0.01). Knockdown of CCAT1-L in MGC803 and MKN-28 cells markedly reduced the cell proliferation, migration, and invasion (P<0.001). CCAT1-L knockdown also evidently inhibited tumor growth and improved survival in nude mice (P<0.001). Expressions of MYC, RAS, and vimentin, and the phosphorylation of ERK protein were dramatically decreased, while the expression of E-cadherin protein was increased by CCAT1-L knockdown in MKN-28 cell.
Conclusion: CCAT1-L is a pro-oncogenic marker in gastric adenocarcinoma. CCAT1-L knockdown inhibits epithelial–mesenchymal transition of gastric adenocarcinoma cells and thus suppresses the gastric adenocarcinoma metastasis.

Keywords: lncRNA CCAT1-L, MYC, gastric adenocarcinoma, EMT

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