Research Paper
Head and Neck Oncology
Down-regulation of hsa_circ_0092125 is related to the occurrence and development of oral squamous cell carcinoma

https://doi.org/10.1016/j.ijom.2019.07.014Get rights and content

Abstract

Circular RNA plays an important role in regulating tumour development and progression and can serve as a biomarker for cancer. This study was performed to investigate the clinical significance of hsa_circ_0092125 expression in oral squamous cell carcinoma (OSCC). The expression of hsa_circ_0092125 in OSCC tissues and cell lines was determined by reverse transcription-quantitative PCR analysis. The association between hsa_circ_0092125 expression and clinicopathological data was determined by χ2 test. Overall survival (OS) curves were created using Kaplan–Meier survival analysis, and the differences were examined by log-rank test. Moreover, univariate and multivariate Cox analysis were employed to evaluate the risk factors of the OSCC prognosis. The expression of hsa_circ_0092125 was significantly down-regulated in OSCC tissues and cell lines. A low expression of hsa_circ_0092125 was associated with clinicopathological factors in OSCC patients, including tumour size, TNM stage, and lymph node metastasis. Kaplan–Meier survival analysis indicated that the OS time was shorter in OSCC patients with a lower hsa_circ_0092125 expression level than in those with a higher expression level. In addition, univariate and multivariate Cox analysis identified lower hsa_circ_0092125 expression, tumour size, TNM stage, and lymph node metastasis as independent risk factors for the OSCC prognosis. Thus, down-regulated expression of hsa_circ_0092125 might serve as a biomarker of the OSCC prognosis.

Section snippets

Patients and tissue specimens

The study was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University (Qingdao, China). Written informed consent was obtained from all participants. A total of 86 patients attending the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Qingdao University, Qingdao, China, were enrolled in this study. In accordance with the National Comprehensive Cancer Network (NCCN) guidelines, tumours were resected with 1.5–2.0 cm of normal tissue outside of the

Expression of hsa_circ_0092125 is down-regulated in OSCC tissues and cells

The expression of hsa_circ_0092125 was detected in the OSCC tissues of all 86 cases and the cell lines using RT-qPCR. The results demonstrated that the expression level of hsa_circ_0092125 in the OSCC tissues was markedly reduced when compared with the level in the matched adjacent normal tissues (Fig. 1A). Moreover, the expression of hsa_circ_0092125 was significantly down-regulated in the human OSCC cell lines (SCC15, SCC25, and CAL27) when compared with the human oral keratinocyte line (HOK)

Discussion

CircRNAs are a novel class of non-coding RNAs comprising a single-stranded RNA molecule with linked ends. They appear to be extremely stable when compared to linear RNAs and are widely expressed in mammals13,16, 17, 18. CircRNAs are considered co-transcriptional products with linear mRNA splicing, and demonstrate heavy dependence on short intronic repeat sequences18, 19, 20. Conceptually, circRNAs can exhibit functionality in two principal ways: firstly, the process of circRNA formation itself,

Funding

This work was supported by the National Science Foundation of China (81502354, 81472520, 81600880), Qingdao/China Postdoctoral Science Foundation (2017M622145, 2017M612217), Source Innovation Planning of Qingdao (17-1-1-42-jch, 17-1-1-45-jch, 18-2-2-77-jch), and Natural Science Foundation of Shaanxi/Shandong Province (2015JM8396, 2016JQ8028, 2017WS215, ZR2018BH021). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Competing interests

None.

Ethical approval

The study protocol conformed to the clinical research guidelines and was approved by the Research Ethics Committee of the Affiliated Hospital of Qingdao University.

Patient consent

Not required.

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      Certain circRNAs showed increased expression in OSCC samples compared with control tissues (onco-circRNAs, including Circ_0001821 and Circ_0002185), and others were downregulated in oral cancer (tumor suppressor circRNAs, such as Circ_0086414, Circ_0072387, Circ_0008309, Circ_001242, and Circ_0092125). The latter molecule also been associated with prognostic parameters (low expression correlated with higher TNM stage, larger tumor size, increased metastatic potential, and decreased survival).71 A recent study showed that circANTRL1 may be associated with enhanced radiosensitivity of oral cancer through inhibition of miR-23a-3p resulting in upregulated expression of PTEN, highlighting the potential of this molecule as a therapeutic target for better response to radiotherapy.72

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    Ling Gao, Qi-Bo Wang, and Yuan Zhi contributed equally to this work and are co-first authors.

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