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Long Noncoding RNA FGD5-AS1 Acts as a Competing Endogenous RNA on microRNA-383 to Enhance the Malignant Characteristics of Esophageal Squamous Cell Carcinoma by Increasing SP1 Expression

Authors Gao J, Zhang Z, Su H, Zong L, Li Y

Received 30 October 2019

Accepted for publication 18 February 2020

Published 26 March 2020 Volume 2020:12 Pages 2265—2278

DOI https://doi.org/10.2147/CMAR.S236576

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Jia Gao,1,* Ziteng Zhang,2,* Hong Su,1 Ling Zong,2 Yan Li1

1Department of Thoracic Surgery, Heze Municipal Hospital, Heze, Shandong 274031, People’s Republic of China; 2Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Shandong 272000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yan Li
Department of Thoracic Surgery, Heze Municipal Hospital, No. 2888 Caozhou West Road, Heze, Shandong 274031, People’s Republic of China
Email yanli_heze@163.com

Purpose: Previous studies have identified the important roles of a long noncoding RNA called FGD5 antisense RNA 1 (FGD5-AS1) in several types of human cancer. Nonetheless, to our knowledge, the expression and functions of FGD5-AS1 in esophageal squamous cell carcinoma (ESCC) have not been clarified. In this study, we aimed to determine the expression status of long noncoding RNA FGD5-AS1 in ESCC, determine its participation in ESCC progression, and uncover the underlying mechanisms.
Methods: ESCC tissue samples and paired normal adjacent tissues were collected to quantify FGD5-AS1 expression by reverse-transcription quantitative PCR. The effects of FGD5-AS1 on ESCC cell proliferation, apoptosis, migration, and invasion in vitro as well as tumor growth in vivo were studied using a Cell Counting Kit-8 assay, flow cytometry, Transwell migration and invasion assays, and an in vivo tumor xenograft experiment.
Results: FGD5-AS1 was found to be aberrantly upregulated in both ESCC tumors and cell lines compared to the control groups. Increased FGD5-AS1 expression manifested a close association with tumor size, TNM stage, and lymph node metastasis in patients with ESCC. Overall survival of patients with ESCC was shorter in the FGD5-AS1 high-expression group than in the FGD5-AS1 low-expression group. An FGD5-AS1 knockdown markedly attenuated ESCC cell proliferation, migration, and invasion and promoted apoptosis in vitro as well as slowed tumor growth in vivo. Mechanism investigation revealed that FGD5-AS1 can increase SP1 expression by sponging microRNA-383 (miR-383), thus functioning as a competing endogenous RNA. An miR-383 knockdown and recovery of SP1 expression attenuated the inhibition of the malignant characteristics of ESCC cells by the FGD5-AS1 knockdown.
Conclusion: Thus, FGD5-AS1 enhances the aggressive phenotype of ESCC cells in vitro and in vivo via the miR-383–SP1 axis, which may represent a novel target for ESCC therapy.

Keywords: esophageal squamous cell carcinoma, FGD5 antisense RNA 1, microRNA-383
 

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