Dataset Information

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

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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7445517 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Zhang Yu Y Tang Kaiqi K Chen Lizhu L Du Meng M Qu Zhi Z

Cancer management and research 20200820

<h4>Background</h4>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.<h4>Methods</h4>Th ...[more]

PMID: 32943917

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Project description:BackgroundCircular RNA RHOT1 (circRHOT1) plays crucial roles in tumorigenesis by competing with microRNAs. It is largely abundant in tumor cell-derived exosomes. Meanwhile, cancer-derived exosomes participate in diverse biological processes. However, the expression patterns and functions of exosomal circRHOT1 in breast cancer remain unknown. This study is aimed to investigate and elucidate the exosomal circRHOT1/miR-204-5p/PRMT5 axis in breast cancer.MethodsThe exosomes derived from serum samples of breast cancer patients and breast cancer cell lines were characterized using transmission electron microscopy and Western blot. MTT, colony formation, wound healing, and transwell assays were utilized to analyze cell proliferation, migration, and invasion of breast cancer cells. Flow cytometry was used for apoptosis analysis. The bioinformatics method was employed to screen differentially expressed novel circRNAs and predict the microRNA targets of circRHOT1. Dual-luciferase reporter gene assays were performed to verify their direct interaction. Finally, Xenograft experiments were used to investigate the effect of exosomal circRHOT1 on tumor growth in vivo.ResultsCircRHOT1 exhibited significantly high expression in exosomes derived from the serum of breast cancer patients and breast cancer cell lines, which suggested its potential diagnostic value. Breast cancer-derived exosomes promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells while inhibiting apoptosis. However, exosomes with downregulated circRHOT1 inhibited the growth of co-cultured cells. Mechanistically, circRHOT1 acted as a sponge of miR-204-5p and promoted protein arginine methyltransferase 5 (PRMT5) expression. Moreover, miR-204-5p inhibitor and pcPRMT5 could reverse the tumor suppressive effects mediated by circRHOT1-knockdown. Furthermore, treatment with exosomes derived from breast cancer cells with circRHOT1 knockdown attenuated tumor growth in tumor-bearing nude mice, which was accompanied by a reduction in PRMT5 expression and an enhancement of miR-204-5p expression.ConclusionThe exosomal circRHOT1 may promote breast cancer progression by regulating the miR-204-5p/PRMT5 axis. The current study strengthens the role of circRHOT1, miR-204-5p, and PRMT5 in breast cancer development and provides a potential treatment strategy for breast cancer.

Dataset Information

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

Publications

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

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