Reduced miRNA‑214 expression in oral mucosa contributes to the pathogenesis of oral lichen planus by targeting CD44

Zheng,Haiyan; Li,Shaohui

doi:10.3892/mmr.2017.8019

Reduced miRNA‑214 expression in oral mucosa contributes to the pathogenesis of oral lichen planus by targeting CD44

Authors:
- Haiyan Zheng
- Shaohui Li
View Affiliations

Affiliations: Department of Dermatology, Jining First People's Hospital, Jining, Shandong 272011, P.R. China, Department of Prosthodontics, Jining Hospital of Stomatology, Jining, Shandong 272001, P.R. China
Published online on: November 10, 2017 https://doi.org/10.3892/mmr.2017.8019
Pages: 1919-1925

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 investigate the role of miRNAs during the pathogenesis of oral lichen planus (OLP). OLP is a chronic inflammatory disorder, which involves T‑cell mediated autoimmunity and affects the skin, scalp, nails and mucosa. Abundant T lymphocytes have been demonstrated to infiltrate the oral mucosa, in which the activated T cells trigger apoptosis of oral epithelial cells. Overexpression of osteopontin (OPN) and CD44 has been observed in the mucosa of patients with OLP, and it has been confirmed that OPN suppresses the apoptosis of activated CD8+ T cells via CD44. The present study initially detected the protein and mRNA expression of CD44 and OPN in the mucosa of patients with OLP by western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and confirmed the previously reported overexpression of CD44 and OPN in patients with OLP. The current study demonstrated, by RT‑qPCR, that the expression of microRNA‑214 (miR‑214), miR‑216a and miR‑216b was significantly reduced in patients with OLP. By analyzing the association between the protein level of CD44 and the expression of microRNAs (miRNAs), the present study identified a negative correlation between the expression of miR‑214 and CD44 in the mucosa samples of patients with OLP. Subsequently, the present study confirmed that miR‑214 represses endogenous CD44 expression by targeting the 3'untranslated region in HeLa, Raji and Jurkat cells. The current study indicates that reduced miR‑214 may be associated with OLP and, therefore, may be a candidate for drug development.

View Figures

View References

1	Khan A, Farah CS, Savage NW, Walsh LJ, Harbrow DJ and Sugerman PB: Th1 cytokines in oral lichen planus. J Oral Pathol Med. 32:77–83. 2003. View Article : Google Scholar
2	Gupta S and Jawanda MK: Oral Lichen Planus: An update on etiology, pathogenesis, clinical presentation, diagnosis and management. Indian J Dermatol. 60:222–229. 2015. View Article : Google Scholar :
3	Dudhia BB, Dudhia SB, Patel PS and Jani YV: Oral lichen planus to oral lichenoid lesions: Evolution or revolution. J Oral Maxillofac Pathol. 19:364–370. 2015. View Article : Google Scholar :
4	Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ and Cantor H: Eta-1 (osteopontin): An early component of type-1 (cell-mediated) immunity. Science. 287:860–864. 2000. View Article : Google Scholar
5	Weber GF, Ashkar S, Glimcher MJ and Cantor H: Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science. 271:509–512. 1996. View Article : Google Scholar
6	Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, Denhardt DT, Sobel RA, Lock C, Karpuj M, Pedotti R, et al: The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science. 294:1731–1735. 2001. View Article : Google Scholar
7	Sakata M, Tsuruha JI, Masuko-Hongo K, Nakamura H, Matsui T, Sudo A, Nishioka K and Kato T: Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol. 28:1492–1495. 2001.
8	Chiocchetti A, Indelicato M, Bensi T, Mesturini R, Giordano M, Sametti S, Castelli L, Bottarel F, Mazzarino MC, Garbarini L, et al: High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation. Blood. 103:1376–1382. 2004. View Article : Google Scholar
9	Zhou ZT, Wei BJ and Shi P: Osteopontin expression in oral lichen planus. J Oral Pathol Med. 37:94–98. 2008. View Article : Google Scholar
10	Santarelli A, Mascitti M, Rubini C, Bambini F, Zizzi A, Offidani A, Ganzetti G, Laino L, Cicciù M and Lo Muzio L: Active inflammatory biomarkers in oral lichen planus. Int J Immunopathol Pharmacol. 28:562–568. 2015. View Article : Google Scholar
11	Friedman RC, Farh KK, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Rese. 19:92–105. 2009. View Article : Google Scholar
12	Gassling V, Hampe J, Açil Y, Braesen JH, Wiltfang J and Häsler R: Disease-associated miRNA-mRNA networks in oral lichen planus. PLoS One. 8:e630152013. View Article : Google Scholar :
13	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
14	van der Waal I, Schepman KP and van der Meij EH: A modified classification and staging system for oral leukoplakia. Oral Oncol. 36:264–266. 2000. View Article : Google Scholar
15	Fischer AH, Jacobson KA, Rose J and Zeller R: Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008:pdb prot4986. 2008.
16	Chanmee T, Ontong P, Kimata K and Itano N: Key roles of Hyaluronan and its CD44 receptor in the stemness and survival of cancer stem cells. Front Oncol. 5:1802015. View Article : Google Scholar :
17	Chaiyarit P, Thongprasom K, Satayut S, Dhanuthai K, Piboonratanakit P, Phothipakdee P, Subarnbhesaj A, Limlertmongkol S and Chaimusig M: Alteration of the expression of CD44 [corrected] isoforms in oral epithelia and saliva from patients with oral lichen planus. J Clin Immunol. 28:26–34. 2008. View Article : Google Scholar
18	Liu GX, Sun JT, Yang MX, Qi XM, Shao QQ, Xie Q, Qu X, Wei FC and Sun SZ: OPN promotes survival of activated T cells by up-regulating CD44 in patients with oral lichen planus. Clin Immunol. 138:291–298. 2011. View Article : Google Scholar
19	Kuninty PR, Bojmar L, Tjomsland V, Larsson M, Storm G, Östman A, Sandström P and Prakash J: MicroRNA-199a and −214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor. Oncotarget. 7:16396–16408. 2016. View Article : Google Scholar :
20	Liu Y, Zhou H, Ma L, Hou Y, Pan J, Sun C, Yang Y and Zhang J: MiR-214 suppressed ovarian cancer and negatively regulated semaphorin 4D. Tumour Biol. 37:8239–8248. 2016. View Article : Google Scholar
21	Xu Y and Lu S: Regulation of β-catenin-mediated esophageal cancer growth and invasion by miR-214. Am J Transl Res. 7:2316–2325. 2015.
22	Yu X, Luo A, Liu Y, Wang S, Li Y, Shi W, Liu Z and Qu X: MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy. Mol Cancer. 14:2082015. View Article : Google Scholar :
23	Phatak P, Byrnes KA, Mansour D, Liu L, Cao S, Li R, Rao JN, Turner DJ, Wang JY and Donahue JM: Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting survivin directly and indirectly through CUG-BP1. Oncogene. 35:2087–2097. 2016. View Article : Google Scholar