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

Abstract

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

Acknowledgments

We thank Dr Li Qinyuan (National Institute of Data Science in Health and Medicine, School of Medicine, Xiamen University) for his help with this study.

Abbreviations

GC, gastric cancer; FGF7, fibroblast growth factor 7; miRNAs, microRNAs; 3ʹ UTR, 3ʹ-untranslated region; RISC, RNA-induced silencing complex; qPCR, quantitative real-time polymerase chain reaction.

Data Sharing Statement

All data generated or analysed during this study are available from the corresponding author on reasonable request.

Ethics Approval and Informed Consent

Written informed consents were obtained from patients and the study was approved by the ethics committee of The First Affiliated Hospital of Xiamen University. All animal experiments were performed under the Chinese animal welfare guidances and were approved by the Animal Research Ethics Committee of The First Affiliated Hospital of Xiamen University.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that there are no conflicts of interest.