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

Abstract

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.

CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis

“… 9 Zhang et al also evidenced that upregulated exosomal circGDI2 decreased OSCC cell malignant behaviors via miR-424-5p/SCAI pathway. 21 These data hinted that circGDI2 might be a possible target for OSCC treatment. Meanwhile, miR-454-3p was validated to be a target of circGDI2.…”

Hsa_circRNA_0001971 contributes to oral squamous cell carcinoma progression via miR‐186‐5p/Fibronectin type III domain containing 3B axis

“…Increasing studies reveal that the abnormal expression of circRNAs is closely associated with OSCC progression; hence, circRNAs are considered as the key biomarkers of OSCC 14,20–22 . For instance, circ_0008309 with low expression was proved to be correlated with pathological differentiation, and circ_0008309 upregulated ATXN1 expression by sponging miR‐136‐5p and miR‐382‐5p in OSCC cells 22 .…”

The Value of Circulating Circular RNA in Cancer Diagnosis, Monitoring, Prognosis, and Guiding Treatment

“…Zhang et al. ( 122 ) also found that exosomal CircGDI2 suppresses oral squamous cell carcinoma progression through the MiR-424-5p/SCAI axis regulation. Thus, exosomes may transport specific circRNAs to target tissue and play a prominent role in cancer intervention treatment.…”