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. 2020 Aug 13;10(1):13739.
doi: 10.1038/s41598-020-70747-y.

Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

Yanwei Luo  1 , Fengxia Liu  1 , Jie Guo  2 , Rong Gui  3
Affiliations

Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

Yanwei Luo et al. Sci Rep. .

Abstract

Studies have found that circRNA in exosomes is associated with oral squamous cell carcinoma (OSCC) progression. In this study, we examined the expression of circ_0000199 in circulating exosomes from patients with OSCC and its role in the evaluation of relapse and prognosis. Real-time quantitative reverse transcription-polymerase chain reaction was performed to assess circ_0000199 expression in circulating exosomes from 108 patients with OSCC and 50 healthy people. Gain- and loss-functional experiments were performed to assess the role of circ_0000199 on cell proliferation and apoptosis in OSCC cells. Our results showed that the high level of circ_0000199 in circulating exosomes was significantly associated with betel quid chewing, tumor size, lymphatic metastasis, and TNM stage in patients with OSCC. In addition, the patients with high exosomal circ_0000199 had higher tumor recurrence rate and higher mortality rate than the patients with low exosomal circ_0000199. Overexpression of circ_0000199 promoted, while knockdown of circ_0000199 inhibited OSCC cell growth. Bioinformatics analysis predicted that circ_0000199 interacted with miR-145-5p and miR-29b-3p simultaneously, which were involved in multiple tumor-related signaling pathways. In conclusion, upregulation of circ_0000199 in circulating exosomes from patients with OSCC is positively associated with poor survival outcome. Circulating exosomal circ_0000199 can be used as a biomarker and potential therapeutic target for OSCC.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Identification of circulating exosomes. (a) The morphology of circulating exosomes (indicated by red arrow) was observed by transmission electron microscopy. (b) The exosome particle size distribution was analyzed using ZetaView. (c) Western blot was performed to test the markers of exosome, TSG101 and CD63. PBS was used as negative control. Ex, exosome. The original blots are presented in Supplementary Fig. 2.
Figure 2
Figure 2
circ_0000199 is upregulated in circulating exosomes from patients with OSCC. (a) qRT-PCR analysis of expression levels of circ_0000199 in circulating exosome from patients with OSCC and healthy subjects. (b) the expression levels of circ_0000199 in circulating exosome in different TNM stage. OSCC, oral squamous cell carcinoma. (c) the overall survival rate was evaluated by Kaplan–Meier curve between OSCC patients with high or low circ_0000199 expression. (d) the disease-free survival rate was evaluated by Kaplan–Meier curve between OSCC patients with high or low circ_0000199 expression.
Figure 3
Figure 3
The effects of circ_0000199 on OSCC cells. (a) qRT-PCR analysis of expression levels of circ_0000199 in OSCC cell lines and HOK cells. (b) qRT-PCR analysis of expression levels of circ_0000199 in SCC9 cells after infection with virus expressed circ_0000199. (c) qRT-PCR analysis of expression levels of circ_0000199 in HN12 cells after infection with virus containing circ_0000199 siRNA. (d) CCK8 was performed to measure cell viability after infection with virus expressed circ_0000199 in SCC9 cells. (e) TUNEL staining was performed to measure apoptotic cells after infection with virus expressed circ_0000199 in SCC9 cells. (f) CCK8 was performed to measure cell viability after infection with virus containing circ_0000199 siRNA in HN12 cells. (g) TUNEL staining was performed to measure apoptotic cells after infection with virus containing circ_0000199 siRNA in HN12 cells. *P < 0.05.
Figure 4
Figure 4
The downstream molecules of circ_0000199. (a) Diagram showing the binding sites for miR‐145‐5p and miR‐29b‐3p in hsa_circ_0072387. (b) The mRNA–miRNA gene co‐expression network. (c) The bar chart shows the top 10 enrichment signaling in biology process, cellular component, molecular function. (d) The bar chart shows the top 10 enrichment KEGG pathways.
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References

    1. Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: Recent advances and future directions. Oral Oncol. 2019;99:104460. doi: 10.1016/j.oraloncology.2019.104460. - DOI - PMC - PubMed
    1. Economopoulou P, de Bree R, Kotsantis I, Psyrri A. Diagnostic tumor markers in head and neck squamous cell carcinoma (HNSCC) in the clinical setting. Front. Oncol. 2019;9:827. doi: 10.3389/fonc.2019.00827. - DOI - PMC - PubMed
    1. Principe S, et al. Tumor-derived exosomes and microvesicles in head and neck cancer: Implications for tumor biology and biomarker discovery. Proteomics. 2013;13:1608–1623. doi: 10.1002/pmic.201200533. - DOI - PubMed
    1. Economopoulou P, Kotsantis I, Kyrodimos E, Lianidou ES, Psyrri A. Liquid biopsy: An emerging prognostic and predictive tool in head and neck squamous cell carcinoma (HNSCC). Focus On circulating tumor cells (CTCS) Oral Oncol. 2017;74:83–89. doi: 10.1016/j.oraloncology.2017.09.012. - DOI - PubMed
    1. Yin Y, et al. Emerging roles of circRNA in formation and progression of cancer. J. Cancer. 2019;10:5015–5021. doi: 10.7150/jca.30828. - DOI - PMC - PubMed

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