circCCDC66 promotes thyroid cancer cell proliferation, migratory and invasive abilities and glycolysis through the miR‑211‑5p/PDK4 axis

Ren,Hong; Song,Zhendi; Chao,Chen; Mao,Weizheng

doi:10.3892/ol.2021.12677

circCCDC66 promotes thyroid cancer cell proliferation, migratory and invasive abilities and glycolysis through the miR‑211‑5p/PDK4 axis

Authors:
- Hong Ren
- Zhendi Song
- Chen Chao
- Weizheng Mao
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Affiliations: Department of General Surgery, Qingdao Municipal Hospital, Qingdao University School of Medicine, Shandong, Qingdao 266000, P.R. China, Department of General Surgery, Jintan Hospital, Jiangsu University School of Medicine, Changzhou, Jiangsu 213200, P.R. China
Published online on: March 26, 2021 https://doi.org/10.3892/ol.2021.12677
Article Number: 416
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cancer metastasis is the main cause of death in cancer patients, including patients with thyroid cancer (TC). TC is the most common malignant endocrine tumour. In the recent years, increasing evidence has demonstrated that circular RNAs (circRNAs) serve a significant role in the development of many types of human cancer. However, the function and underlying mechanism of circCCDC66 in TC remain unclear. The present study aimed to explore the role of circCCDC66 in TC. To do so, reverse transcription quantitative PCR was used to detect the expression level of circCCDC66. Cell viability, migratory and invasive abilities, and glucose consumption were evaluated by cell counting kit 8, Transwell and glucose consumption assays, respectively. The association between circCCDC66 or pyruvate dehydrogenase kinase 4 (PDK4) and miR‑211‑5p was verified by dual‑luciferase reporter assay. The results demonstrated that circCCDC66 expression was significantly increased in TC tissues and cell lines. Furthermore, silencing circCCDC66 inhibited TC cell proliferation, migratory and invasive abilities and glycolysis in vitro. Further validation demonstrated that circCCDC66 directly interacted with the microRNA (miR) miR‑211‑5p. Subsequently, the activity of circCCDC66 was attenuated by miR‑211‑5p. In addition, the results demonstrated that circCCDC66 may promote papillary thyroid cancer progression by sponging miR‑211‑5p and increasing expression of PDK4. In conclusion, the present study demonstrated that circCCDC66 could promote TC cell proliferation, migratory and invasive abilities and invasion and glycolysis through the miR‑211‑5p/PDK4 axis. These findings suggested that targeting circCCDC66 may be considered as a promising therapeutic strategy for TC.

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1	Zhang JW, Long KR, Wang X, LI MZ and Ma JD: The research advance of circular RNA. Chin J Anim Veterinary Sci,. 11:2151–2158. 2016.(In Chinese).
2	Cai H, Li Y, Niringiyumukiza JD, Su P and Xiang W: Circular RNA involvement in aging: An emerging player with great potential. Mech Ageing Dev. 178:16–24. 2019. View Article : Google Scholar : PubMed/NCBI
3	Lu Q, Liu T, Feng H, Yang R, Zhao X, Chen W, Jiang B, Qin H, Guo X, Liu M, et al: Circular RNA circSLC8A1 acts as a sponge of miR-130b/miR-494 in suppressing bladder cancer progression via regulating PTEN. Mol Cancer. 18:1112019. View Article : Google Scholar : PubMed/NCBI
4	Xu JZ, Shao CC, Wang XJ, Zhao X, Chen JQ, Ouyang YX, Feng J, Zhang F, Huang WH, Ying Q, et al: circTADA2As suppress breast cancer progression and metastasis via targeting miR-203a-3p/SOCS3 axis. Cell Death Dis. 10:1752019. View Article : Google Scholar : PubMed/NCBI
5	Lu J, Wang YH, Yoon C, Huang XY, Xu Y, Xie JW, Wang JB, Lin JX, Chen QY, Cao LL, et al: Circular RNA circ-RanGAP1 regulates VEGFA expression by targeting miR-877-3p to facilitate gastric cancer invasion and metastasis. Cancer Lett. 471:38–48. 2020. View Article : Google Scholar : PubMed/NCBI
6	Gaffo E, Boldrin E, Dal Molin A, Bresolin S, Bonizzato A, Trentin L, Frasson C, Debatin KM, Meyer LH, Te Kronnie G and Bortoluzzi S: Circular RNA differential expression in blood cell populations and exploration of circRNA deregulation in pediatric acute lymphoblastic leukemia. Sci Rep. 9:146702019. View Article : Google Scholar : PubMed/NCBI
7	Xiong X, Zhu H and Chen X: Low expression of long noncoding RNA CASC2 indicates a poor prognosis and promotes tumorigenesis in thyroid carcinoma. Biomed Pharmacother. 93:391–397. 2017. View Article : Google Scholar : PubMed/NCBI
8	Li S, Li Z, Guo F, Qin X, Liu B, Lei Z, Song Z, Sun L, Zhang HT, You J and Zhou Q: MiR-223 regulates migration and invasion by targeting Artemin in human esophageal carcinoma. J Biomed Sci. 18:242011. View Article : Google Scholar : PubMed/NCBI
9	Du WW, Yang W, Liu E, Yang Z, Dhaliwal P and Yang BB: Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res. 44:2846–2858. 2016. View Article : Google Scholar : PubMed/NCBI
10	Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ and Cooper DS: The diagnosis and management of Thyroid Nodules: A review. JAMA. 319:914–924. 2018. View Article : Google Scholar : PubMed/NCBI
11	Cong S, Fang LW, Bao HL, Feng YJ, Wang N, Yin P, Li YC, Duan XN and Zhou MG: (Disease burden of thyroid cancer in the Chinese population, in 1990 and 2013). Zhonghua Liu Xing Bing Xue Za Zhi. 37:773–777. 2016.PubMed/NCBI
12	Schmidt B and Davies L: The rising incidence of thyroid cancer: Contributions from healthcare practice and biologic risk factors. Management of Differentiated Thyroid Cancer. Springer; Cham: pp. 1–13. 2017, View Article : Google Scholar
13	Murugan AK, Dong J, Xie J and Xing M: MEK1 mutations, but not ERK2 mutations, occur in melanomas and colon carcinomas, but none in thyroid carcinomas. Cell Cycle. 8:2122–2124. 2009. View Article : Google Scholar : PubMed/NCBI
14	Gao Y, Wang J, Zheng Y, Zhang J, Chen S and Zhao F: Comprehensive identification of internal structure and alternative splicing events in circular RNAs. Nat Commun. 7:120602016. View Article : Google Scholar : PubMed/NCBI
15	Wei H, Pan L, Tao D and Li R: Circular RNA circZFR contributes to papillary thyroid cancer cell proliferation and invasion by sponging miR-1261 and facilitating C8orf4 expression. Biochem Biophys Res Commun. 503:56–61. 2018. View Article : Google Scholar : PubMed/NCBI
16	Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS and Tsai SJ: Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis. Cancer Res. 77:2339–2350. 2017. View Article : Google Scholar : PubMed/NCBI
17	Hong W, Yu S, Zhuang Y, Zhang Q, Wang J and Gao X: SRCIN1 regulated by circCCDC66/miR-211 is upregulated and promotes cell proliferation in non-small-cell lung cancer. Biomed Res Int. 2020:53076412020. View Article : Google Scholar : PubMed/NCBI
18	Xiang D, Li Y and Lin Y: Circular RNA circCCDC66 contributes to malignant phenotype of osteosarcoma by Sponging miR-338-3p to upregulate the expression of PTP1B. Biomed Res Int. 2020:46371092020. View Article : Google Scholar : PubMed/NCBI
19	Wang M, Chen B, Ru Z and Cong L: CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway. Biochem Biophys Res Commun. 504:283–288. 2018. View Article : Google Scholar : PubMed/NCBI
20	Xu H, Liu Y, Cheng P, Wang C, Liu Y, Zhou W, Xu Y and Ji G: CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis. J Exp Clin Cancer Res. 39:2832020. View Article : Google Scholar : PubMed/NCBI
21	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
22	Nahm JH, Kim HM and Koo JS: Glycolysis-related protein expression in thyroid cancer. Tumour Biol. 39:10104283176959222017. View Article : Google Scholar : PubMed/NCBI
23	Wang Y, Zhou X, Shan B, Han J, Wang F, Fan X, Lv Y, Chang L and Liu W: Downregulation of microRNA-33a promotes cyclin-dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation. Mol Med Rep. 12:6491–6500. 2015. View Article : Google Scholar : PubMed/NCBI
24	Kim Y, Williams KC, Gavin CT, Jardine E, Chambers AF and Leong HS: Quantification of cancer cell extravasation in vivo. Nat Protoc. 11:937–948. 2016. View Article : Google Scholar : PubMed/NCBI
25	Wang KW and Dong M: Role of circular RNAs in gastric cancer: Recent advances and prospects. World J Gastrointest Oncol. 11:459–469. 2019. View Article : Google Scholar : PubMed/NCBI
26	Cui S, Qian Z, Chen Y, Li L, Li P and Ding H: Screening of up- and downregulation of circRNAs in HBV-related hepatocellular carcinoma by microarray. Oncol Lett. 15:423–432. 2018.PubMed/NCBI
27	Chen LL, Zhang ZJ, Yi ZB and Li JJ: MicroRNA-211-5p suppresses tumour cell proliferation, invasion, migration and metastasis in triple-negative breast cancer by directly targeting SETBP1. Br J Cancer. 117:78–88. 2017. View Article : Google Scholar : PubMed/NCBI
28	Wang K, Jin W, Jin P, Fei X, Wang X and Chen X: MiR-211-5p suppresses metastatic behavior by targeting SNAI1 in Renal cancer. Mol Cancer Res. 15:448–456. 2017. View Article : Google Scholar : PubMed/NCBI
29	Jiang G, Wen L, Deng W, Jian Z and Zheng H: Regulatory role of miR-211-5p in hepatocellular carcinoma metastasis by targeting ZEB2. Biomed Pharmacother. 90:806–812. 2017. View Article : Google Scholar : PubMed/NCBI
30	Shan C, Kang HB, Elf S, Xie J, Gu TL, Aguiar M, Lonning S, Hitosugi T, Chung TW, Arellano M, et al: Tyr-94 phosphorylation inhibits pyruvate dehydrogenase phosphatase 1 and promotes tumor growth. J Biol Chem. 289:21413–21422. 2014. View Article : Google Scholar : PubMed/NCBI
31	Sui W, Shi Z, Xue W, Ou M, Zhu Y, Chen J, Lin H, Liu F and Dai Y: Circular RNA and gene expression profiles in gastric cancer based on microarray chip technology. Oncol Rep. 37:1804–1814. 2017. View Article : Google Scholar : PubMed/NCBI
32	Sun S, Zhao M, Han Y, Juanzi W, Peng W and Liu J: PDK4 mRNA Expression in Breast Cancer and Its Relationship with Prognosis. Cancer Res Prev Treat. 45:73–76. 2018.
33	Mazar J, Richardson A, Qi F, Lee B, Duran A, Govindarajan S, Shelley J, Brill LM, Li JL, Han X, Moscat J and Perera RJ: MicroRNA-211 modulates energy metabolism in human melanoma cells by destabilizing HIF1-α and downregulating PDK4. AACR. 74:S9782014.