lncRNA SOX2‑OT regulates laryngeal cancer cell proliferation, migration and invasion and induces apoptosis by suppressing miR‑654

Li,Guang; Pan,Chunchen; Sun,Jiaqiang; Wan,Guanglun; Sun,Jingwu

doi:10.3892/etm.2020.8577

lncRNA SOX2‑OT regulates laryngeal cancer cell proliferation, migration and invasion and induces apoptosis by suppressing miR‑654

Authors:
- Guang Li
- Chunchen Pan
- Jiaqiang Sun
- Guanglun Wan
- Jingwu Sun
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Affiliations: School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Otorhinolaryngology‑Head and Neck Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China
Published online on: March 6, 2020 https://doi.org/10.3892/etm.2020.8577
Pages: 3316-3324
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Laryngeal carcinoma is the most common type of malignant tumor in the head and neck. Long non‑coding RNAs (lncRNAs) serve crucial roles in numerous biological processes. The present study aimed to investigate the role of lncRNA SOX2‑OT in laryngeal cancer and to reveal the underlying mechanisms. Reverse transcription‑quantitative PCR assays were used to measure the expression levels of SOX2‑OT in the laryngeal cell lines. Furthermore, cell proliferation, apoptosis, migration and invasion were assessed by CCK‑8, flow cytometry, wound healing and Transwell assays, respectively. Western blot assay was performed to detect the protein expressions. In addition, a dual‑luciferase reporter assay was performed to confirm the direct interaction between SOX2‑OT and microRNA (miR)‑654. The data demonstrated that SOX2‑OT level were significantly increased in the laryngeal cell lines. Furthermore, SOX2‑OT silencing markedly promoted apoptosis and suppressed the proliferation, migration and invasion of TU‑177 cells. A dual‑luciferase reporter assay revealed that miR‑654 was a direct target of SOX2‑OT. Moreover, downregulation of miR‑654 could attenuate cell apoptosis and accelerate cell proliferation, migration and invasion in TU‑177 cells. In summary, the present study reported that knockdown of SOX2‑OT could suppress cell proliferation, migration and invasion, and induce apoptosis in laryngeal cancer by targeting miR‑654.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar
2	Steuer CE, El-Deiry M, Parks JR, Higgins KA and Saba NF: An update on larynx cancer. CA Cancer J Clin. 67:31–50. 2017.PubMed/NCBI View Article : Google Scholar
3	Ferlito A, Devaney KO, Hunt JL and Hellquist H: Some considerations on the WHO histological classification of laryngeal neoplasms. Adv Ther. 36:1511–1517. 2019.PubMed/NCBI View Article : Google Scholar
4	Wu CW, Dionigi G, Barczynski M, Chiang FY, Dralle H, Schneider R, Al-Quaryshi Z, Angelos P, Brauckhoff K, Brooks JA, et al: International neuromonitoring study group guidelines 2018: Part II: Optimal recurrent laryngeal nerve management for invasive thyroid cancer-incorporation of surgical, laryngeal, and neural electrophysiologic data. Laryngoscope. 128 (Suppl 3):S18–S27. 2018.PubMed/NCBI View Article : Google Scholar
5	Calkovsky V, Wallenfels P, Calkovska A and Hajtman A: Laryngeal cancer: 12-year experience of a single center. Adv Exp Med Biol. 911:9–16. 2016.PubMed/NCBI View Article : Google Scholar
6	Laccourreye O, Bonfils P, Malinvaud D, Ménard M and Giraud P: Survival and laryngeal preservation tradeoff in advanced laryngeal cancer: From the otorhinolaryngology patient to the managing physician. Head Neck. 39:1984–1989. 2017.PubMed/NCBI View Article : Google Scholar
7	Yang G, Lu X and Yuan L: lncRNA: A link between RNA and cancer. Biochim Biophys Acta. 1839:1097–1109. 2014.PubMed/NCBI View Article : Google Scholar
8	Sang H, Liu H, Xiong P and Zhu M: Long non-coding RNA functions in lung cancer. Tumour Biol. 36:4027–4037. 2015.PubMed/NCBI View Article : Google Scholar
9	Teng Y, Kang H and Chu Y: Identification of an exosomal long noncoding RNA SOX2-OT in plasma as a promising biomarker for lung squamous cell carcinoma. Genet Test Mol Biomarkers. 23:235–240. 2019.PubMed/NCBI View Article : Google Scholar
10	Wang Z, Tan M, Chen G, Li Z and Lu X: lncRNA SOX2-OT is a novel prognostic biomarker for osteosarcoma patients and regulates osteosarcoma cells proliferation and motility through modulating SOX2. IUBMB Life. 69:867–876. 2017.PubMed/NCBI View Article : Google Scholar
11	Wei CX, Wong H, Xu F, Liu Z, Ran L and Jiang RD: IRF4-induced upregulation of lncRNA SOX2-OT promotes cell proliferation and metastasis in cholangiocarcinoma by regulating SOX2 and PI3K/AKT signaling. Eur Rev Med Pharmacol Sci. 22:8169–8178. 2018.PubMed/NCBI View Article : Google Scholar
12	Feng L, Wang R, Lian M, Ma H, He N, Liu H, Wang H and Fang J: Integrated analysis of long noncoding RNA and mRNA expression profile in advanced laryngeal squamous cell carcinoma. PLoS One. 11(e0169232)2016.PubMed/NCBI View Article : Google Scholar
13	Tai Y, Ji Y, Liu F, Zang Y, Xu D, Ma S, Qin L and Ma J: Long noncoding RNA SOX2-OT facilitates laryngeal squamous cell carcinoma development by epigenetically inhibiting PTEN via methyltransferase EZH2. IUBMB Life. 71:1230–1239. 2019.PubMed/NCBI View Article : Google Scholar
14	Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009.PubMed/NCBI View Article : Google Scholar
15	Zhang N, Lu C and Chen L: miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer. Oncol Lett. 12:4589–4597. 2016.PubMed/NCBI View Article : Google Scholar
16	Cybula M, Wieteska L-, Józefowicz-Korczyńska M, Karbownik MS, Grzelczyk WL and Szemraj J: New miRNA expression abnormalities in laryngeal squamous cell carcinoma. Cancer Biomark. 16:559–568. 2016.PubMed/NCBI View Article : Google Scholar
17	Wang FY, Jia J, Song HH, Jia CM, Chen CB and Ma J: Icariin protects vascular endothelial cells from oxidative stress through inhibiting endoplasmic reticulum stress. J Integr Med. 17:205–212. 2019.PubMed/NCBI View Article : Google Scholar
18	Shields EJ, Petracovici AF and Bonasio R: lncRedibly versatile: Biochemical and biological functions of long noncoding RNAs. Biochem J. 476:1083–1104. 2019.PubMed/NCBI View Article : Google Scholar
19	Xie ZY, Wang P, Wu YF and Shen HY: Long non-coding RNA: The functional regulator of mesenchymal stem cells. World J Stem Cells. 11:167–179. 2019.PubMed/NCBI View Article : Google Scholar
20	Xu J, Bai J, Zhang X, Lv Y, Gong Y, Liu L, Zhao H, Yu F, Ping Y, Zhang G, et al: A comprehensive overview of lncRNA annotation resources. Brief Bioinform. 18:236–249. 2017.PubMed/NCBI View Article : Google Scholar
21	Sparber P, Filatova A, Khantemirova M and Skoblov M: The role of long non-coding RNAs in the pathogenesis of hereditary diseases. BMC Med Genomics. 12 (Suppl 2):S422019.PubMed/NCBI View Article : Google Scholar
22	Peng WX, Koirala P and Mo YY: lncRNA-mediated regulation of cell signaling in cancer. Oncogene. 36:5661–5667. 2017.PubMed/NCBI View Article : Google Scholar
23	Lu M, Wang C, Chen W, Mao C and Wang J: miR-654-5p targets GRAP to promote proliferation, metastasis, and chemoresistance of oral squamous cell carcinoma through Ras/MAPK signaling. DNA Cell Biol. 37:381–388. 2018.PubMed/NCBI View Article : Google Scholar
24	Jin P, Huang Y, Zhu P, Zou Y, Shao T and Wang O: CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling. Biochem Biophys Res Commun. 503:1570–1574. 2018.PubMed/NCBI View Article : Google Scholar
25	Dhulipala VC, Welshons WV and Reddy CS: Cell cycle proteins in normal and chemically induced abnormal secondary palate development: A review. Hum Exp Toxicol. 25:675–682. 2006.PubMed/NCBI View Article : Google Scholar
26	Zatonski T, Ciesielska U, Nowinska K, Ratajczak-Wielgomas K, Kobierzycki C, Pula B, Podhorska-Okolow M, Krecicki T and Dziegiel P: Expression of cell cycle-related proteins p16, p27, p53 and Ki-67 in HPV-positive and -negative samples of papillomas of the upper respiratory tract. Anticancer Res. 36:3917–3924. 2016.PubMed/NCBI
27	Lee EF, Harris TJ, Tran S, Evangelista M, Arulananda S, John T, Ramnac C, Hobbs C, Zhu H, Gunasingh G, et al: BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival. Cell Death Dis. 10(342)2019.PubMed/NCBI View Article : Google Scholar
28	Chrysovergis A, S Papanikolaou V, Tsiambas E, Kikidis D, Maragoudakis P, Ragos V and Kyrodimos E: Caspase complex in laryngeal squamous cell carcinoma. J BUON. 24:1–4. 2019.PubMed/NCBI
29	Lotfi A, Mohammadi G, Saniee L, Mousaviagdas M, Chavoshi H and Tavassoli A: Serum level of matrix metalloproteinase-2 and -9 in patients with laryngeal squamous cell carcinoma and clinical significance. Asian Pac J Cancer Prev. 16:6749–6751. 2015.PubMed/NCBI View Article : Google Scholar
30	Uloza V, Liutkevičius V, Pangonytė D, Saferis V and Lesauskaitė V: Expression of matrix metalloproteinases (MMP-2 and MMP-9) in recurrent respiratory papillomas and laryngeal carcinoma: Clinical and morphological parallels. Eur Arch Otorhinolaryngol. 268:871–878. 2011.PubMed/NCBI View Article : Google Scholar