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Exosomal CircGDI2 Suppresses Oral Squamous Cell Carcinoma Progression Through the Regulation of MiR-424-5p/SCAI Axis

Authors Zhang Y, Tang K, Chen L, Du M, Qu Z

Received 26 March 2020

Accepted for publication 29 July 2020

Published 20 August 2020 Volume 2020:12 Pages 7501—7514

DOI https://doi.org/10.2147/CMAR.S255687

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava


Yu Zhang, Kaiqi Tang, Lizhu Chen, Meng Du, Zhi Qu

Department of Prosthetics, The Second Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China

Correspondence: Zhi Qu
Department of Prosthetics, The Second Affiliated Hospital of Jinzhou Medical University, No. 49, Section 2, Shanghai Road, Guta District, Jinzhou City, Liaoning Province 121000, People’s Republic of China
Tel +86 41 62655049
Email wangkang2137@163.com

Background: Exosomes are small membrane vesicles that are secreted by most cell types. Circular RNAs (circRNAs) have recently been identified in exosomes, and exosomal circRNAs exert important biological activities in human cancers, including oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate whether circRNA GDP dissociation inhibitor 2 (circGDI2) was transferred by exosomes and how exosomal circGDI2 regulated OSCC cell malignant behaviors.
Methods: The levels of circGDI2, miR-424-5p and suppressor of cancer cell invasion (SCAI) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Transwell assays were performed to detect cell migration and invasion. Measurement of glucose consumption and lactate production were conducted using a corresponding assay kit. Targeted correlations among circGDI2, miR-424-5p and SCAI were confirmed by dual-luciferase reporter assays. Xenograft assays were used to observe the role of circGDI2 in tumor growth in vivo.
Results: Our data indicated that circGDI2 was down-regulated in OSCC, and it could be transferred by the exosomes in OSCC cells. The up-regulation of exosomal circGDI2 weakened OSCC cell proliferation, migration, invasion and glycolysis. CircGDI2 functioned as a molecular sponge of miR-424-5p, and SCAI was a direct target of miR-424-5p. MiR-424-5p mediated the repression of exosomal circGDI2 overexpression on OSCC cell malignant behaviors, and miR-424-5p silencing mitigated OSCC cell progression by up-regulating SCAI. Moreover, exosomal circGDI2 regulated SCAI expression through sponging miR-424-5p. Additionally, the overexpression of exosomal circGDI2 inhibited tumor growth in vivo.
Conclusion: The present study had led to the identification of exosomal circGDI2 that regulated OSCC cell malignant behaviors through targeting the miR-424-5p/SCAI axis, highlighting circGDI2 as a novel exosome-based cancer biomarker and therapeutic agent for OSCC treatment.

Keywords: OSCC, exosome, circGDI2, miR-424-5p, SCAI

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