Circular RNA expression profiling identifies specific circular RNAs in tongue squamous cell carcinoma

Wei,Tai; Ye,Peng; Yu,Guang‑Yan; Zhang,Zu‑Yan

doi:10.3892/mmr.2020.10980

Circular RNA expression profiling identifies specific circular RNAs in tongue squamous cell carcinoma

Authors:
- Tai Wei
- Peng Ye
- Guang‑Yan Yu
- Zu‑Yan Zhang
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Affiliations: First Clinical Division, Peking University Hospital of Stomatology, Beijing 100034, P.R. China, Department of Stomatology, Beijing Hospital, National Centre of Gerontology, Beijing 100730, P.R. China, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100181, P.R. China
Published online on: February 6, 2020 https://doi.org/10.3892/mmr.2020.10980
Pages: 1727-1738
Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tongue squamous cell carcinoma (TSCC) is the most frequent type of oral cancer associated with high malignancy. Circular RNAs (circRNAs) are a form of non‑coding RNA with stable and conserved expression in mammalian cells. The aim of the present study was to investigate circRNAs expression profiles in TSCC, and examine the roles and potential mechanisms of circRNA‑081069 (circ_081069). A high‑throughput circRNA microarray analysis of tumor samples and adjacent normal tissues from four patients with TSCC was performed. Bioinformatic analysis was conducted to screen the differentially expressed circRNAs. Reverse transcription‑quantitative PCR was performed to confirm the microarray results. A migration assay and proliferation assay were performed to detect the migratory and proliferative ability of TSCC cells. A luciferase assay was conducted to investigate the interaction between circ_081069 and microRNA (miRNA/miR)‑665. In total, 335 circRNAs were found to be differentially expressed in tumor tissues. Among them, 59 were upregulated and 276 were downregulated (P<0.05; fold change ≥2 or ≤0.5). A total of seven circRNAs, including two upregulated and five downregulated circRNAs, were further confirmed using quantitative PCR analysis in the ten paired TSCC tissues and adjacent normal tissues. The present study showed that circRNA_081069 promoted the migratory and proliferative ability of TSCC cells in vitro. Furthermore, the potential circRNA‑miRNA interactions were predicted, and the present results identified miR‑665 as a miRNA target of circ_081069. The present results suggested that circRNAs may be involved in TSCC development, and understanding the interaction between circ_081069 and miR‑665 may facilitate the development of novel diagnostic and therapeutic targets for TSCC.

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1	Patel RS, Clark JR, Dirven R, Wyten R, Gao K and O'Brien CJ: Prognostic factors in the surgical treatment of patients with oral carcinoma. ANZ J Surg. 79:19–22. 2009. View Article : Google Scholar : PubMed/NCBI
2	Yuen PW, Lam KY, Chan AC, Wei WI and Lam LK: Clinicopathological analysis of local spread of carcinoma of the tongue. Am J Surg. 175:242–244. 1998. View Article : Google Scholar : PubMed/NCBI
3	Rodriguez T, Altieri A, Chatenoud L, Gallus S, Bosetti C, Negri E, Franceschi S, Levi F, Talamini R and Lavecchia C: Risk factors for oral and pharyngeal cancer in young adults. Oral Oncol. 40:207–213. 2004. View Article : Google Scholar : PubMed/NCBI
4	Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, et al: Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495:333–338. 2013. View Article : Google Scholar : PubMed/NCBI
5	Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF and Sharpless NE: Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 19:141–157. 2013. View Article : Google Scholar : PubMed/NCBI
6	Ebbesen KK, Hansen TB and Kjems J: Insights into circular RNA biology. RNA Biol. 14:1035–1045. 2017. View Article : Google Scholar : PubMed/NCBI
7	Wang Y, Mo Y, Gong Z, Yang X, Yang M, Zhang S, Xiong F, Xiang B, Zhou M, Liao Q, et al: Circular RNAs in human cancer. Mol Cancer. 16:252017. View Article : Google Scholar : PubMed/NCBI
8	Hansen TB, Kjems J and Damgaard CK: Circular RNA and miR-7 in cancer. Cancer Res. 73:5609–5612. 2013. View Article : Google Scholar : PubMed/NCBI
9	Dong R, Zhang XO, Zhang Y, Ma XK, Chen LL and Yang L: CircRNA-derived pseudogenes. Cell Res. 26:747–750. 2016. View Article : Google Scholar : PubMed/NCBI
10	Brierley JD, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumours. 8th. Wiley; Chichester: 2017
11	Wu HJ, Zhang CY, Zhang S, Chang M and Wang HY: Microarray expression profile of circular RNAs in heart tissue of mice with myocardial infarction-induced heart failure. Cell Physiol Biochem. 39:205–216. 2016. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Guo XH, Wang JY, Gao Y, Gao M, Yu GY, Xiang RL, Li L, Yang NY, Cong X, Xu XY, et al: Decreased adiponectin level is associated with aggressive phenotype of tongue squamous cell carcinoma. Cancer Sci. 104:206–213. 2013. View Article : Google Scholar : PubMed/NCBI
14	Dong C, Du Q, Wang Z, Wang Y, Wu S and Wang A: MicroRNA-665 suppressed the invasion and metastasis of osteosarcoma by directly inhibiting RAB23. Am J Transl Res. 8:4975–4981. 2016.PubMed/NCBI
15	Zhang Y, Yang L, Wang S, Liu Z and Xiu M: MiR-29a suppresses cell proliferation by targeting SIRT1 in hepatocellular carcinoma. Cancer Biomark. 22:151–159. 2018. View Article : Google Scholar : PubMed/NCBI
16	Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, Chen D, Gu J, He X and Huang S: Circular RNA is enriched and stable in exosomes: A promising biomarker for cancer diagnosis. Cell Res. 25:981–984. 2015. View Article : Google Scholar : PubMed/NCBI
17	Dou Y, Cha DJ, Franklin JL, Higginbotham JN, Jeppesen DK, Weaver AM, Prasad N, Levy S, Coffey RJ, Patton JG and Zhang B: Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes. Sci Rep. 6:379822016. View Article : Google Scholar : PubMed/NCBI
18	Lasda E and Parker R: Circular RNAs co-precipitate with extracellular vesicles: A possible mechanism for circRNA clearance. PLoS One. 11:e01484072016. View Article : Google Scholar : PubMed/NCBI
19	Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL and Yang L: Complementary sequence-mediated exon circularization. Cell. 159:134–147. 2014. View Article : Google Scholar : PubMed/NCBI
20	Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L and Chen LL: Circular intronic long noncoding RNAs. Mol Cell. 51:792–806. 2013. View Article : Google Scholar : PubMed/NCBI
21	Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, Zhong G, Yu B, Hu W, Dai L, et al: Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 22:256–264. 2015. View Article : Google Scholar : PubMed/NCBI
22	Qin M, Liu G, Huo X, Tao X, Sun X, Ge Z, Yang J, Fan J, Liu L and Qin W: Has circ 0001649: A circular RNA and potential novel biomarker for hepatocellular carcinoma. Cancer Biomark. 16:161–169. 2016. View Article : Google Scholar : PubMed/NCBI
23	Xu Y, Yao Y, Zhong X, Leng K, Qin W, Qu L, Cui Y and Jiang X: Downregulated circular RNA has circ 0001649 regulates proliferation, migration and invasion in cholangiocarcinoma cells. Biochem Biophys Res Commun. 496:455–461. 2018. View Article : Google Scholar : PubMed/NCBI
24	Li WH, Song YC, Zhang H, Zhou ZJ, Xie X, Zeng QN, Guo K, Wang T, Xia P and Chang DM: Decreased expression of has circ 00001649 in gastric cancer and its clinical significance. Dis Markers. 2017:45876982017. View Article : Google Scholar : PubMed/NCBI
25	Liu Y, Lu C, Zhou Y, Zhang Z and Sun L: Circular RNA has circ 0008039 promotes breast cancer cell proliferation and migration by regulating miR-432-5p/E2F3 axis. Biochem Biophys Res Commun. 3:358–363. 2018. View Article : Google Scholar
26	Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, Luo Y, Lyu D, Li Y, Shi G, et al: Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 7:112152016. View Article : Google Scholar : PubMed/NCBI
27	Chen L, Zhang S, Wu J, Cui J, Zhong L, Zeng L and Ge S: CircRNA 100290 plays a role in oral cancer by functioning as a sponge of the miR-29 family. Oncogene. 36:4551–4561. 2017. View Article : Google Scholar : PubMed/NCBI
28	Liu X, Lv X, Yang Q, Jin H, Zhou W and Fan Q: MicroRNA-29a functions as a tumor suppressor and increases cisplatin sensitivity by targeting NRAS in lung cancer. Technol Cancer Res Treat. 17:15330338187589052018. View Article : Google Scholar : PubMed/NCBI