The differential regulation of microRNAs is associated with oral cancer

Tsai,Shih-Chang; Huang,Sheng-Fong; Chiang,Jo-Hua; Chen,Yen-Fu; Huang,Chia-Chang; Tsai,Ming-Hsui; Tsai,Fuu-Jen; Kao,Ming-Ching; Yang,Jai-Sing

doi:10.3892/or.2017.5811

The differential regulation of microRNAs is associated with oral cancer

Authors:
- Shih-Chang Tsai
- Sheng-Fong Huang
- Jo-Hua Chiang
- Yen-Fu Chen
- Chia-Chang Huang
- Ming-Hsui Tsai
- Fuu-Jen Tsai
- Ming-Ching Kao
- Jai-Sing Yang
View Affiliations

Affiliations: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C., Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi County, Taiwan, R.O.C., Department of Otolaryngology, China Medical University Hospital, Taichung, Taiwan, R.O.C., Human Genetic Center, China Medical University Hospital, Taichung, Taiwan, R.O.C., Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
Published online on: July 12, 2017 https://doi.org/10.3892/or.2017.5811
Pages: 1613-1620

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

Oral squamous cell carcinoma (OSCC), is the most frequently occurring malignant head and neck tumor, generally it exhibits a poor prognosis, and metastasis is the main cause of death in these cancer patients. The discovery of reliable prognostic indicators for tumors progression would greatly improve clinical treatments. MicroRNAs (miRNAs) play a critical role in the degradation of mRNA and the inhibition of protein synthesis. The miRNAs function either as tumor suppressors or as oncogenes in tumorigenesis, and little is known about the clinical significance of miRNA expression profiles in oral cancers. In the present study, we investigated the expression profiles of miR-375, miR-204 and miR-196a in 39 healthy and tumor tissue pairs of oral cancer patients using TaqMan real-time quantitative polymerase chain reaction (qPCR). The predicted target genes for miR-375, miR-204 and miR-196a were confirmed using luciferase reporter-based assays and western blot analyses. In oral cancer tissue, the expression of miR-375 and miR-204 decreased, whereas the expression of miR-196a was significantly elevated. In OSCC, HOXB8 and p27 (CDKN1B) were the direct target genes of miR-196a, whereas HMGA2 was the direct target gene of miR-204. HOXB8 and p27 (CDKN1B) protein expression levels were inhibited by miR-196a, whereas the protein expression level of HMGA2 was inhibited by miR-204. Furthermore, the miR-196a inhibitor blocked cell proliferation. Our results indicate that the combined expression signatures of miR-375, miR-204 and miR-196a are promising biomarkers for the diagnosis, prognosis and treatment of OSCC.

View Figures

View References

1	Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 45:309–316. 2009. View Article : Google Scholar : PubMed/NCBI
2	Camisasca DR, Silami MA, Honorato J, Dias FL, de Faria PA and Lourenço SQ: Oral squamous cell carcinoma: Clinicopathological features in patients with and without recurrence. ORL J Otorhinolaryngol Relat Spec. 73:170–176. 2011. View Article : Google Scholar : PubMed/NCBI
3	Chang CH, Lee CY, Lu CC, Tsai FJ, Hsu YM, Tsao JW, Juan YN, Chiu HY, Yang JS and Wang CC: Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling. Int J Oncol. 50:873–882. 2017.PubMed/NCBI
4	Yuan CH, Horng CT, Lee CF, Chiang NN, Tsai FJ, Lu CC, Chiang JH, Hsu YM, Yang JS and Chen FA: Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling. Environ Toxicol. 32:845–855. 2017. View Article : Google Scholar : PubMed/NCBI
5	Tovosia S, Chen PH, Ko AM, Tu HP, Tsai PC and Ko YC: Prevalence and associated factors of betel quid use in the Solomon Islands: A hyperendemic area for oral and pharyngeal cancer. Am J Trop Med Hyg. 77:586–590. 2007.PubMed/NCBI
6	Chiang SL, Jiang SS, Wang YJ, Chiang HC, Chen PH, Tu HP, Ho KY, Tsai YS, Chang IS and Ko YC: Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci. 100:66–74. 2007. View Article : Google Scholar : PubMed/NCBI
7	Chang SS, Jiang WW, Smith I, Poeta LM, Begum S, Glazer C, Shan S, Westra W, Sidransky D and Califano JA: MicroRNA alterations in head and neck squamous cell carcinoma. Int J Cancer. 123:2791–2797. 2008. View Article : Google Scholar : PubMed/NCBI
8	Scapoli L, Palmieri A, Lo Muzio L, Pezzetti F, Rubini C, Girardi A, Farinella F, Mazzotta M and Carinci F: MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression. Int J Immunopathol Pharmacol. 23:1229–1234. 2010. View Article : Google Scholar : PubMed/NCBI
9	Gorenchtein M, Poh CF, Saini R and Garnis C: MicroRNAs in an oral cancer context - from basic biology to clinical utility. J Dent Res. 91:440–446. 2011. View Article : Google Scholar : PubMed/NCBI
10	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
11	Hammond SM: MicroRNAs as oncogenes. Curr Opin Genet Dev. 16:4–9. 2006. View Article : Google Scholar : PubMed/NCBI
12	Yu FS, Yang JS, Yu CS, Lu CC, Chiang JH, Lin CW and Chung JG: Safrole induces apoptosis in human oral cancer HSC-3 cells. J Dent Res. 90:168–174. 2011. View Article : Google Scholar : PubMed/NCBI
13	Tsai SC and Seto E: Regulation of histone deacetylase 2 by protein kinase CK2. J Biol Chem. 277:31826–31833. 2002. View Article : Google Scholar : PubMed/NCBI
14	Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D and Seto E: Histone deacetylase interacts directly with DNA topoisomerase II. Nat Genet. 26:349–353. 2000. View Article : Google Scholar : PubMed/NCBI
15	Huang WW, Chiu YJ, Fan MJ, Lu HF, Yeh HF, Li KH, Chen PY, Chung JG and Yang JS: Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathway in human osteosarcoma U-2 OS cells. Mol Nutr Food Res. 54:1585–1595. 2010. View Article : Google Scholar : PubMed/NCBI
16	Huang SH, Wu LW, Huang AC, Yu CC, Lien JC, Huang YP, Yang JS, Yang JH, Hsiao YP, Wood WG, et al: Benzyl isothiocyanate (BITC) induces G2/M phase arrest and apoptosis in human melanoma A375.S2 cells through reactive oxygen species (ROS) and both mitochondria-dependent and death receptor-mediated multiple signaling pathways. J Agric Food Chem. 60:665–675. 2012. View Article : Google Scholar : PubMed/NCBI
17	Lai KC, Huang AC, Hsu SC, Kuo CL, Yang JS, Wu SH and Chung JG: Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/−9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway. J Agric Food Chem. 58:2935–2942. 2010. View Article : Google Scholar : PubMed/NCBI
18	Liao CL, Lai KC, Huang AC, Yang JS, Lin JJ, Wu SH, Wood W Gibson, Lin JG and Chung JG: Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/−9, protein kinase B (PKB) and PKC signaling pathways. Food Chem Toxicol. 50:1734–1740. 2012. View Article : Google Scholar : PubMed/NCBI
19	Ma YS, Weng SW, Lin MW, Lu CC, Chiang JH, Yang JS, Lai KC, Lin JP, Tang NY, Lin JG, et al: Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: Roles of apoptotic cell death and LS1034 tumor xenografts model. Food Chem Toxicol. 50:1271–1278. 2012. View Article : Google Scholar : PubMed/NCBI
20	Kato H, Uzawa K, Onda T, Kato Y, Saito K, Nakashima D, Ogawara K, Bukawa H, Yokoe H and Tanzawa H: Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma. Int J Oncol. 28:873–881. 2006.PubMed/NCBI
21	Mello CC and Czech MP: Micromanaging insulin secretion. Nat Med. 10:1297–1298. 2004. View Article : Google Scholar : PubMed/NCBI
22	El Ouaamari A, Baroukh N, Martens GA, Lebrun P, Pipeleers D and van Obberghen E: miR-375 targets 3-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes. 57:2708–2717. 2008. View Article : Google Scholar : PubMed/NCBI
23	Conte I, Carrella S, Avellino R, Karali M, Marco-Ferreres R, Bovolenta P and Banfi S: miR-204 is required for lens and retinal development via Meis2 targeting. Proc Natl Acad Sci USA. 107:15491–15496. 2010. View Article : Google Scholar : PubMed/NCBI
24	Lee Y, Yang X, Huang Y, Fan H, Zhang Q, Wu Y, Li J, Hasina R, Cheng C, Lingen MW, et al: Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis. PLOS Comput Biol. 6:e10007302010. View Article : Google Scholar : PubMed/NCBI
25	Kim YJ, Bae SW, Yu SS, Bae YC and Jung JS: miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res. 24:816–825. 2009. View Article : Google Scholar : PubMed/NCBI
26	Luthra R, Singh RR, Luthra MG, Li YX, Hannah C, Romans AM, Barkoh BA, Chen SS, Ensor J, Maru DM, et al: MicroRNA-196a targets annexin A1: A microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene. 27:6667–6678. 2008. View Article : Google Scholar : PubMed/NCBI
27	Schimanski CC, Frerichs K, Rahman F, Berger M, Lang H, Galle PR, Moehler M and Gockel I: High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World J Gastroenterol. 15:2089–2096. 2009. View Article : Google Scholar : PubMed/NCBI
28	Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, et al: A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 432:226–230. 2004. View Article : Google Scholar : PubMed/NCBI
29	Shi W, Yang J, Li S, Shan X, Liu X, Hua H, Zhao C, Feng Z, Cai Z, Zhang L, et al: Potential involvement of miR-375 in the premalignant progression of oral squamous cell carcinoma mediated via transcription factor KLF5. Oncotarget. 6:40172–40185. 2015. View Article : Google Scholar : PubMed/NCBI
30	Avissar M, McClean MD, Kelsey KT and Marsit CJ: MicroRNA expression in head and neck cancer associates with alcohol consumption and survival. Carcinogenesis. 30:2059–2063. 2009. View Article : Google Scholar : PubMed/NCBI
31	Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, et al: MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 24:4677–4684. 2006. View Article : Google Scholar : PubMed/NCBI
32	Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, Volinia S, Liu CG, Schnittger S, Haferlach T, et al: Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci USA. 105:3945–3950. 2008. View Article : Google Scholar : PubMed/NCBI
33	Yekta S, Shih IH and Bartel DP: MicroRNA-directed cleavage of HOXB8 mRNA. Science. 304:594–596. 2004. View Article : Google Scholar : PubMed/NCBI
34	Vider BZ, Zimber A, Hirsch D, Estlein D, Chastre E, Prevot S, Gespach C, Yaniv A and Gazit A: Human colorectal carcinogenesis is associated with deregulation of homeobox gene expression. Biochem Biophys Res Commun. 232:742–748. 1997. View Article : Google Scholar : PubMed/NCBI
35	Cheng AM, Byrom MW, Shelton J and Ford LP: Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 33:1290–1297. 2005. View Article : Google Scholar : PubMed/NCBI
36	Kudo Y, Kitajima S, Ogawa I, Miyauchi M and Takata T: Down-regulation of Cdk inhibitor p27 in oral squamous cell carcinoma. Oral Oncol. 41:105–116. 2005. View Article : Google Scholar : PubMed/NCBI
37	Wu BH, Xiong XP, Jia J and Zhang WF: MicroRNAs: New actors in the oral cancer scene. Oral Oncol. 47:314–319. 2011. View Article : Google Scholar : PubMed/NCBI