miR‑204 enhances p27 mRNA stability by targeting Brd4 in head and neck squamous cell carcinoma

Wang,Caihua; Zhang,Yonghong; Zhou,Dayong; Cao,Guanjie; Wu,Yungang

doi:10.3892/ol.2018.9180

miR‑204 enhances p27 mRNA stability by targeting Brd4 in head and neck squamous cell carcinoma

Authors:
- Caihua Wang
- Yonghong Zhang
- Dayong Zhou
- Guanjie Cao
- Yungang Wu
View Affiliations

Affiliations: Department of Ear, Nose and Throat, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272000, P.R. China, Department of Orthopedics, Hengkang Hospital, Jining, Shandong 272000, P.R. China, Department of Imaging, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272000, P.R. China
Published online on: July 19, 2018 https://doi.org/10.3892/ol.2018.9180
Pages: 4179-4184
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

The present study aimed to explore the function of microRNA (miR)‑204 in modulating cyclin‑dependent kinase inhibitor 1B (p27) mRNA stability in head and neck squamous cell carcinoma (HNSCC). Briefly, reverse transcription quantitative polymerase chain reaction and western blot analysis were used to detect miR‑204 and Brd4 level. Cell viability, cell cycle and cell apoptosis were used to investigate the effects of miR‑204. Additional luciferase reporter and mRNA stability assays were used to explore the mechanisms contributing to miR‑204 effects. Here, miR‑204 was downregulated in HNSCC tissues compared with the adjacent normal tissues. The expression levels of miR‑204 and bromodomain‑containing protein 4 (Brd4) were negatively associated in HNSCC tissues. Ectopic expression of miR‑204 inhibited HNSCC cell proliferation, promoted cell cycle arrest at the G1/S phase and promoted cell apoptosis compared with control cells. Additionally, upregulation of miR‑204 expression levels enhanced p27 mRNA stability. Notably, Brd4 was identified as a target of miR‑204, and the co‑expression of Brd4 with miR‑204 mimics attenuated the inhibitory effects of miR‑204 on cell proliferation and enhanced p27 mRNA stability compared with control cells. Thus, it was concluded that miR‑204 functions as a tumor suppressor by enhancing p27 mRNA stability through targeting Brd4 in HNSCC.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Datta J, Islam M, Dutta S, Roy S, Pan Q and Teknos TN: Suberoylanilide hydroxamic acid inhibits growth of head and neck cancer cell lines by reactivation of tumor suppressor microRNAs. Oral Oncol. 56:32–39. 2016. View Article : Google Scholar : PubMed/NCBI
3	Li X, Zheng L, Zhang F, Hu J, Chou J, Liu Y, Xing Y and Xi T: STARD13-correlated ceRNA network inhibits EMT and metastasis of breast cancer. Oncotarget. 7:23197–23211. 2016.PubMed/NCBI
4	Zheng L, Li X, Gu Y, Lv X and Xi T: The 3′UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1. Breast Cancer Res Treat. 150:105–118. 2015. View Article : Google Scholar : PubMed/NCBI
5	Ye ZN, Liu JP, Wu LY, Zhang XS, Zhuang Z, Chen Q, Lu Y, Liu CG, Zhang ZH, Zhang HS, et al: Downregulation of miR-204 expression correlates with poor clinical outcome of glioma patients. Hum Pathol. 63:46–52. 2017. View Article : Google Scholar : PubMed/NCBI
6	Canu V, Sacconi A, Lorenzon L, Biagioni F, Lo Sardo F, Diodoro MG, Muti P, Garofalo A, Strano S, D'Errico A, et al: MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer. Oncotarget. 8:29540–29557. 2017. View Article : Google Scholar : PubMed/NCBI
7	Butrym A, Rybka J, Baczynska D, Tukiendorf A, Kuliczkowski K and Mazur G: Low expression of microRNA-204 (miR-204) is associated with poor clinical outcome of acute myeloid leukemia (AML) patients. J Exp Clin Cancer Res. 34:682015. View Article : Google Scholar : PubMed/NCBI
8	Wang L, Matkar S, Xie G, An C, He X, Kong X, Liu X and Hua X: BRD4 inhibitor IBET upregulates p27kip/cip protein stability in neuroendocrine tumor cells. Cancer Biol Ther. 18:229–236. 2017. View Article : Google Scholar : PubMed/NCBI
9	Shao J, Li S, Palmqvist L, Fogelstrand L, Wei SY, Busayavalasa K, Liu K and Liu VM: p27(KIP1) and PTEN cooperate in myeloproliferative neoplasm tumor suppression in mice. Exp Hematol Oncol. 5:172016. View Article : Google Scholar : PubMed/NCBI
10	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
11	Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, et al: Selective inhibition of BET bromodomains. Nature. 468:1067–1073. 2010. View Article : Google Scholar : PubMed/NCBI
12	Shi L, Zhang B, Sun X, Lu S, Liu Z, Liu Y, Li H, Wang L, Wang X and Zhao C: MiR-204 inhibits human NSCLC metastasis through suppression of NUAK1. Br J Cancer. 111:2316–2327. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yin Y, Zhang B, Wang W, Fei B, Quan C, Zhang J, Song M, Bian Z, Wang Q, Ni S, et al: miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A. Clin Cancer Res. 20:6187–6199. 2014. View Article : Google Scholar : PubMed/NCBI
14	Zeng J, Wei M, Shi R, Cai C, Liu X, Li T and Ma W: MiR-204-5p/Six1 feedback loop promotes epithelial-mesenchymal transition in breast cancer. Tumour Biol. 37:2729–2735. 2016. View Article : Google Scholar : PubMed/NCBI
15	Sun Y, Yu X and Bai Q: miR-204 inhibits invasion and epithelial-mesenchymal transition by targeting FOXM1 in esophageal cancer. Int J Clin Exp Pathol. 8:12775–12783. 2015.PubMed/NCBI
16	Gao X, Wu X, Zhang X, Hua W and Zhang Y, Maimaiti Y, Gao Z and Zhang Y: Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer. Biochem Biophys Res Commun. 469:679–685. 2016. View Article : Google Scholar : PubMed/NCBI
17	Hu Y, Zhou J, Ye F, Xiong H, Peng L, Zheng Z, Xu F, Cui M, Wei C, Wang X, et al: BRD4 inhibitor inhibits colorectal cancer growth and metastasis. Int J Mol Sci. 16:1928–1948. 2015. View Article : Google Scholar : PubMed/NCBI