Silencing Long Non-Coding RNA AGAP2-AS1 Upregulates microRNA-195-5p to Repress Migration and Invasion of Esophageal Cancer Cells Via the Decrease of FOSL1 Expression

Abstract

Background: The involvement of long non-coding RNAs (lncRNAs) has been highlighted in multiple cancers including esophageal cancer (EC). Differentially expressed Our study aims to figure out the role of AGAP2-AS1/microRNA-195-5p (miR-195-5p)/FOSL1 in the EC progression. Methods: The expression of AGAP2-AS1, miR-195-5p and FOSL1 in EC tissues and EC cell lines were determined. After that, the ectopic expression and knockdown were applied to explore effect of AGAP2-AS1/miR-195-5p/FOSL1 on EC cell proliferation, cell cycle and apoptosis, as well as invasion and migration. Moreover, xenograft tumor model of nude mice was utilized for verification of the in vitro results. Results: EC tissues and cells were found to contain increased AGAP2-AS1 and FOSL1 and decreased miR-195-5p. AGAP2-AS1 knockdown or miR-195-5p overexpression reduced EC cell proliferation, migration and invasion, blocked cell cycle entry, as well as increased apoptosis. AGAP2-AS1 was observed to down-regulate FOSL1 by binding to miR-195-5p to suppress the development of EC, which was also confirmed in vivo. Conclusions: It was concluded that AGAP2-AS1 downregulation exhibited suppressive effects on the development of EC by decreasing miR-195-5p-dependent FOSL1, highlighting a future direction to develop a novel treatment strategy. Funding: This study was supported by “Ubiquitin-proteasome pathway gene SNPs and paclitaxel sensitivity in advanced esophageal squamous cell carcinoma” (No. 81201954). Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: Written informed consent was obtained from all patients prior to the study. Study protocols were approved by Ethic Committee of Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital) following the Helsinki Declaration. Animal experiments were conducted in strict accordance with the Guide to the Management and Use of Laboratory Animals issued by the National Institutes of Health. The protocol of animal experiments was approved by the Institutional Animal Care and Use Committee of Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital).