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MiR-548d-3p Promotes Gastric Cancer by Targeting RSK4

Authors Liang H, Hu C, Lin X, He Z, Lin Z, Dai J

Received 25 August 2020

Accepted for publication 4 December 2020

Published 24 December 2020 Volume 2020:12 Pages 13325—13337

DOI https://doi.org/10.2147/CMAR.S278691

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Bilikere Dwarakanath


Hui Liang,* Cong Hu,* Xu Lin, Zhuocheng He, Zhiwen Lin, Jun Dai

General Surgery Department, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hui Liang
General Surgery Department, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Xiangzhou District, Zhuhai 519000, Guangdong, People’s Republic of China
Tel +86 0756-2158341
Email JohnnyDr_hu@hotmail.com

Purpose: Previous studies have demonstrated that RSK4 inhibits the proliferation of gastric cancer cells and the occurrence of tumors. However, to date, studies involving microRNAs (miRNAs) that target RSK4 have rarely been reported. Thus, this study aimed to investigate the miRNAs that target RSK4.
Materials and Methods: We screened miRNAs related to RSK4 in miRDB, microT-CDS, TargetScan, and mirDIP databases and found 18 miRNAs. We chose miR-548d-3p for follow-up research, identified the interaction site in RSK4 by comparing the sequence, and mutated it. Thereafter, we used the dual-luciferase reporter system, real-time PCR (RT-PCR), and Western blotting to assess the effect of miR-548d-3p on RSK4. The proliferation, apoptosis, migration, and invasion of gastric cancer cells were evaluated using MTT assay, propidium iodide (PI), EdU, annexin V-FITC/PI apoptosis detection kit, wound healing assay, and transwell assay after overexpression of miR-548d-3p and RSK4. Finally, a nude mouse tumorigenesis experiment was conducted to explore the role of RSK4-targeting miR-548d-3p in tumorigenesis.
Results: miR-548d-3p negatively regulated the expression of RSK4, resulting in suppressed apoptosis, enhanced proliferation, migration, and invasion of gastric cancer cells, and accelerated tumor growth. In addition, an increase in miR-548d-3p expression enhanced the mRNA levels of CDK2, cyclin A1, cyclin D1, Bax, Bcl-2, N-cadherin, and Vimentin, and decreased E-cadherin mRNA levels by targeting RSK4.
Conclusion: miR-548d-3p promotes gastric cancer by lowering the expression of RSK4.

Keywords: microRNA, gastric cancer, RSK4, miR-548d-3p

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