Microarray profile of circular RNAs identifies hsa_circRNA_102459 and hsa_circRNA_043621 as important regulators in oral squamous cell carcinoma

Deng,Wei; Peng,Wei; Wang,Tao; Chen,Jingxin; Qiu,Xunding; Fu,Liangbin; Zhu,Shuangxi

doi:10.3892/or.2019.7369

Microarray profile of circular RNAs identifies hsa_circRNA_102459 and hsa_circRNA_043621 as important regulators in oral squamous cell carcinoma

Authors:
- Wei Deng
- Wei Peng
- Tao Wang
- Jingxin Chen
- Xunding Qiu
- Liangbin Fu
- Shuangxi Zhu
View Affiliations

Affiliations: Department of Oral and Maxillofacial Surgery, Hainan General Hospital, Haikou, Hainan 570311, P.R. China, Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: October 14, 2019 https://doi.org/10.3892/or.2019.7369
Pages: 2738-2749

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Circular RNAs (circRNAs) have emerged as important regulators of carcinogenesis. However, the role of circRNAs in oral squamous cell carcinoma (OSCC) remains limited. Here, total RNAs were extracted from three pairs of OSCC and adjacent normal tissues and subjected to circRNA microarrays to detect the differentially expressed circRNAs. Gene Ontology (GO) and functional category analyses were used to identify circRNAs associated with tumor cell proliferation pathways. Then, gain‑of‑function assays or loss‑of‑function assays were conducted to investigate the functions of the most upregulated and downregulated circRNAs on TSCC1 cell proliferation, cell cycle and apoptosis using CCK‑8 and EdU assays, flow cytometry and Hoechst 33258 staining, respectively. The results revealed that hsa_circRNA_102459 was significantly downregulated and hsa_circRNA_043621 was significantly upregulated in OSCC tissues. Clinical stage, tumor differentiation, lymph node metastasis presented significant difference in regards to the expression of circRNA_043621 and circRNA_102459. The in vitro experiments further demonstrated that upregulation of circRNA_102459 or downregulation of circRNA_043621 significantly suppressed TSCC1 cell proliferation, induced cell cycle G0/G1 phase arrest and promoted apoptosis. Furthermore, the MAPK and PI3K/Akt pathways were suppressed, while Bcl‑2 family members were activated by circRNA_102459 overexpression and circRNA_043621 knockdown. Taken together, our study indicates that differentially expressed circRNAs are closely related to the carcinogenesis of OSCC. Among these, circRNA_102459 and circRNA_043621 may function as a tumor‑suppressor and promoter, respectively, of OSCC carcinogenesis, and thus may be valuable diagnostic biomarkers of OSCC.

View Figures

View References

1	Mignogna MD, Fedele S and Lo Russo L: The world cancer report and the burden of oral cancer. Eur J Cancer Prev. 13:139–142. 2004. View Article : Google Scholar : PubMed/NCBI
2	van Zyl A and Bunn BK: Clinical features of oral cancer. SADJ. 67:566–569. 2012.PubMed/NCBI
3	Blatt S, Kruger M, Ziebart T, Sagheb K, Schiegnitz E, Goetze E, Al-Nawas B and Pabst AM: Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: A review of the literature. J Craniomaxillofac Surg. 45:722–730. 2017. View Article : Google Scholar : PubMed/NCBI
4	Zhao X, Sun S, Zeng X and Cui L: Expression profiles analysis identifies a novel three-mRNA signature to predict overall survival in oral squamous cell carcinoma. Am J Cancer Res. 8:450–461. 2018.PubMed/NCBI
5	Wilusz JE and Sharp PA: Molecular biology. A circuitous route to noncoding RNA. Science. 340:440–441. 2013. View Article : Google Scholar : PubMed/NCBI
6	Hentze MW and Preiss T: Circular RNAs: Splicing's enigma variations. EMBO J. 32:923–925. 2013. View Article : Google Scholar : PubMed/NCBI
7	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
8	Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, Li X and Yang BB: Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J. 38:1402–1412. 2017.PubMed/NCBI
9	Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z and Sharpless NE: Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet. 6:e10012332010. View Article : Google Scholar : PubMed/NCBI
10	Lukiw WJ: Circular RNA (circRNA) in Alzheimer's disease (AD). Front Genet. 4:3072013. View Article : Google Scholar : PubMed/NCBI
11	Zhang J, Zhao X, Zhang J, Zheng X and Li F: Circular RNA hsa_circ_0023404 exerts an oncogenic role in cervical cancer through regulating miR-136/TFCP2/YAP pathway. Biochem Biophys Res Commun. 22:428–433. 2018. View Article : Google Scholar
12	Li P, Yang X, Yuan W, Yang C, Zhang X, Han J, Wang J, Deng X, Yang H, Li P, et al: CircRNA-Cdr1as exerts anti-oncogenic functions in bladder cancer by sponging microRNA-135a. Cell Physiol Biochem. 46:1606–1616. 2018. View Article : Google Scholar : PubMed/NCBI
13	Liu W, Ma W, Yuan Y, Zhang Y and Sun S: Circular RNA hsa_circRNA_103809 promotes lung cancer progression via facilitating ZNF121-dependent MYC expression by sequestering miR-4302. Biochem Biophys Res Commun. 500:846–851. 2018. View Article : Google Scholar : PubMed/NCBI
14	Wang L, Wei Y, Yan Y, Wang H, Yang J, Zheng Z, Zha J, Bo P, Tang Y, Guo X, et al: CircDOCK1 suppresses cell apoptosis via inhibition of miR196a5p by targeting BIRC3 in OSCC. Oncol Rep. 39:951–966. 2018.PubMed/NCBI
15	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
16	Galasso M, Costantino G, Pasquali L, Minotti L, Baldassari F, Corrà F, Agnoletto C and Volinia S: Profiling of the predicted circular RNAs in ductal in situ and invasive breast cancer: A pilot study. Int J Genomics. 2016:45038402016. View Article : Google Scholar : PubMed/NCBI
17	Nair AA, Niu N, Tang X, Thompson KJ, Wang L, Kocher JP, Subramanian S and Kalari KR: Circular RNAs and their associations with breast cancer subtypes. Oncotarget. 7:809672016. View Article : Google Scholar : PubMed/NCBI
18	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
19	Hou P, Liu D, Shan Y, Hu S, Studeman K, Condouris S, Wang Y, Trink A, El-Naggar AK and Tallini G: Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res. 13:11612007. View Article : Google Scholar : PubMed/NCBI
20	Li S, Ma YM, Zheng PS and Zhang P: GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2. J Exp Clin Cancer Res. 37:802018. View Article : Google Scholar : PubMed/NCBI
21	Robinson DR, Kalyana-Sundaram S, Wu YM, Shankar S, Cao X, Ateeq B, Asangani IA, Iyer M, Maher CA, Grasso CS, et al: Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer. Nat Med. 17:1646–1651. 2011. View Article : Google Scholar : PubMed/NCBI
22	Wang LX, Li Y and Chen GZ: Network-based co-expression analysis for exploring the potential diagnostic biomarkers of metastatic melanoma. PLoS One. 13:e01904472018. View Article : Google Scholar : PubMed/NCBI
23	Zheng Y, Zhao G, Xu B, Liu C, Li C, Zhang X and Chang X: PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-α expression levels. Oncotarget. 7:62159–62176. 2016. View Article : Google Scholar : PubMed/NCBI
24	Na Y, Kaul SC, Ryu J, Lee JS, Ahn HM, Kaul Z, Kalra RS, Li L, Widodo N, Yun CO and Wadhwa R: Stress chaperone mortalin contributes to epithelial-mesenchymal transition and cancer metastasis. Cancer Res. 76:2754–2765. 2016. View Article : Google Scholar : PubMed/NCBI
25	Yu C, Liu SL, Qi MH, Zou X, Wu J and Zhang J: Herbal medicine guan chang fu fang enhances 5-fluorouracil cytotoxicity and affects drug-associated genes in human colorectal carcinoma cells. Oncol Lett. 9:701–708. 2015. View Article : Google Scholar : PubMed/NCBI
26	Brunelle JK and Letai A: Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 122:437–441. 2009. View Article : Google Scholar : PubMed/NCBI