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Upregulation of Linc-ROR Promotes the Proliferation, Migration, and Invasion of Gastric Cancer Cells Through miR-212-3p/FGF7 Axis

Authors Mi Y, Li Y, He Z, Chen D, Hong Q, You J

Received 20 October 2020

Accepted for publication 24 December 2020

Published 2 February 2021 Volume 2021:13 Pages 899—912

DOI https://doi.org/10.2147/CMAR.S287775

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Yanjun Mi,1,* Yongwen Li,2,* Zhuo He,3,* Donghan Chen,2 Qingqi Hong,2 Jun You2

1Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People’s Republic of China; 3Department of Gastropancreatoduodenal Surgery, Hunan Cancer Hospital, Changsha, Hunan Province, 410013, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jun You
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, No. 55 Zhenhai Road, Si Ming District, Xiamen, Fujian Province, 361003, People’s Republic of China
Tel +86 13906051681
Email youjun1681@163.com

Background: Linc-ROR is a long non-coding RNA, that is found aberrantly expressed in various human cancers. We aim here to unveil the role of Linc-ROR in gastric cancer (GC) progression.
Methods: qPCR was used to determine gene expression. Cell viability was measured by CCK-8 assay. Transwell assays were performed to evaluate the GC cells’ migratory and invasive abilities. Xenograft mouse model was conducted to measure tumor growth.
Results: We found that Linc-ROR were overexpressed in GC tissues compared to the adjacent tissues. High Linc-ROR predicts poor prognosis of GC patients. The prediction of bioinformatics online revealed that Linc-ROR could bind to miR-212-3p. Further, dual-luciferase reporter assay confirmed a direct interaction between Linc-ROR and miR-212-3p. Overexpression of miR-212-3p facilitated GC cells’ migration and invasion, while the silencing of miR-212-3p attenuated GC cell migratory and invasive abilities. Moreover, Linc-ROR knockdown significantly suppressed the proliferation, migration, and invasion of GC cells, whereas miR-212-3p antagomir partially reversed Linc-ROR knockdown-induced phenotypes. Fibroblast growth factor 7 (FGF7), a downstream molecule of miR-212-3p, was overexpressed in GC cells. The recovery of FGF7 expression partially reversed the phenotypes caused by Linc-ROR silencing. Mechanistically, silencing of Linc-ROR contributed to the downregulation of CDK4, CDK6, Cyclin D1, N-Cadherin, Vimentin, MMP-9, MMP-2, but caused the upregulation of P21, P27, E-Cadherin, CK-19 in MGC-803 cells; however, FGF7 treatment could reverse the results induced by Linc-ROR silencing. Results in vivo further suggested that Linc-ROR knockdown repressed GC tumor growth, where the expression of miR-212-3p was up-regulated and FGF7 expression was downregulated in tumor tissues of mice.
Conclusion: These findings indicated that Linc-ROR/miR-212-3p/FGF7 axis played an important role in gastric cancer progression. Linc-ROR expression level was associated with the prognosis of GC patients.

Keywords: Linc-ROR, miR-212-3p, FGF7, gastric cancer

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