Salivary mir-27b Expression in Oral Lichen Planus Patients: A Series of Cases and a Narrative Review of Literature

Author(s): Dario Di Stasio, Laura Mosca, Alberta Lucchese*, Donatella Delle Cave, Hiromichi Kawasaki, Angela Lombardi, Marina Porcelli, Michele Caraglia.

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 31 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: microRNAs play a critical role in auto-immunity, cell proliferation, differentiation and cell death. miRNAs are present in all biological fluids, and their expression is essential in maintaining regular immune functions and preventing autoimmunity, whereas miRNA dysregulation may be associated with the pathogenesis of autoimmune and inflammatory diseases. Oral lichen planus (OLP) is an inflammatory disease mediated by cytotoxic T cells attack against epithelial cells. The present study aims to perform a specific microRNA expression profile through the analysis of saliva in this disease.

Methods: The study group was formed by five patients (mean age 62.8±1.98 years; 3 females/2 males) affected by oral lichen planus and control group by five healthy subjects (mean age 59.8 years±2.3; 3 females/ 2 males); using a low-density microarray analysis, we recorded a total of 98 differentially expressed miRNAs in the saliva of patients with oral lichen planus compared to the control group. The validation was performed for miR-27b with qRT-PCR in all saliva samples of oral lichen planus group.

Results: 89 miRNAs were up-regulated and nine down-regulated. In details, levels of miR-21, miR- 125b, miR-203 and miR15b were increased (p<0.001) in study group while levels of miR-27b were about 3.0-fold decreased compared to controls (p<0.001) of miR-27b expression in OLP saliva. QRTPCR validation confirmed the down regulation of miR-27b in all saliva samples.

Conclusion: Collecting saliva samples is a non-invasive procedure and is well accepted by all patients. microRNAs can be readily isolated and identified and can represent useful biomarkers of OLP.

Keywords: miRNAs, OLP, Saliva, Micro Array, miR-27b, Keratinocytes.

[1]
Cheng, Y.S.L.; Gould, A.; Kurago, Z.; Fantasia, J.; Muller, S. Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology. Oral Surg. Oral Med. Oral Pathol. Oral Radiol., 2016, 122(3), 332-354.
[http://dx.doi.org/10.1016/j.oooo.2016.05.004] [PMID: 27401683]
[2]
Lucchese, A.; Dolci, A.; Minervini, G.; Salerno, C.D.I.; Stasio, D.; Minervini, G.; Laino, L.; Silvestre, F.; Serpico, R. Vulvovaginal gingival lichen planus: report of two cases and review of literature. Oral Implantol. (Rome), 2016, 9(2), 54-60.
[PMID: 28042431]
[3]
Danielsson, K.; Boldrup, L.; Rentoft, M.; Coates, P.J.; Ebrahimi, M.; Nylander, E.; Wahlin, Y.B.; Nylander, K. Autoantibodies and decreased expression of the transcription factor ELF-3 together with increased chemokine pathways support an autoimmune phenotype and altered differentiation in lichen planus located in oral mucosa. J. Eur. Acad. Dermatol. Venereol., 2013, 27(11), 1410-1416.
[http://dx.doi.org/10.1111/jdv.12027] [PMID: 23134363]
[4]
Boccellino, M.; Di Stasio, D.; Romano, A.; Petruzzi, M.; Lucchese, A.; Serpico, R.; Frati, L.; Di Domenico, M. Lichen planus: molecular pathway and clinical implications in oral disorders. J. Biol. Regul. Homeost. Agents, 2018, 32(2)(Suppl. 1), 135-138.
[PMID: 29460532]
[5]
Shiohara, T.; Mizukawa, Y.; Takahashi, R.; Kano, Y. Pathomechanisms of lichen planus autoimmunity elicited by cross-reactive T Cells. Dermatologic Immunity; KARGER: Basel, 2008, Vol. 10, pp. 206-226.
[http://dx.doi.org/10.1159/000131456]
[6]
Zhang, W-Y.; Liu, W.; Zhou, Y-M.; Shen, X-M.; Wang, Y-F.; Tang, G-Y. Altered microRNA expression profile with miR-27b down-regulation correlated with disease activity of oral lichen planus. Oral Dis., 2012, 18(3), 265-270.
[http://dx.doi.org/10.1111/j.1601-0825.2011.01869.x] [PMID: 22077423]
[7]
Wang, L.; Wu, W.; Chen, J.; Li, Y.; Xu, M.; Cai, Y. MicroRNA microarray-based identification of involvement of miR-155 and miR-19a in development of oral lichen planus (OLP) by modulating Th1/Th2 balance via Targeting eNOS and toll-like receptor 2 (TLR2). Med. Sci. Monit., 2018, 24, 3591-3603.
[http://dx.doi.org/10.12659/MSM.907497] [PMID: 29813046]
[8]
Tao, Y.; Ai, R.; Hao, Y.; Jiang, L.; Dan, H.; Ji, N.; Zeng, X.; Zhou, Y.; Chen, Q. Role of miR-155 in immune regulation and its relevance in oral lichen planus. Exp. Ther. Med., 2019, 17(1), 575-586.
[PMID: 30651838]
[9]
Hu, J-Y.; Zhang, J.; Ma, J-Z.; Liang, X-Y.; Chen, G-Y.; Lu, R.; Du, G-F.; Zhou, G. MicroRNA-155-IFN-γ feedback loop in CD4(+)T cells of erosive type oral lichen planus. Sci. Rep., 2015, 5, 16935.
[http://dx.doi.org/10.1038/srep16935] [PMID: 26594049]
[10]
Danielsson, K.; Wahlin, Y.B.; Gu, X.; Boldrup, L.; Nylander, K. Altered expression of miR-21, miR-125b, and miR-203 indicates a role for these microRNAs in oral lichen planus. J. Oral Pathol. Med., 2012, 41(1), 90-95.
[http://dx.doi.org/10.1111/j.1600-0714.2011.01084.x] [PMID: 21943223]
[11]
Gassling, V.; Hampe, J.; Açil, Y.; Braesen, J.H.; Wiltfang, J.; Häsler, R.; Acil, Y.; Braesen, J.H.; Wiltfang, J.J.; Hasler, R. Disease-associated miRNA-mRNA networks in oral lichen planus. PLoS One, 2013, 8(5)e63015
[http://dx.doi.org/10.1371/journal.pone.0063015] [PMID: 23723971]
[12]
He, L.; Hannon, G.J. MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet., 2004, 5(7), 522-531.
[http://dx.doi.org/10.1038/nrg1379] [PMID: 15211354]
[13]
Ivey, K.N.; Srivastava, D. MicroRNAs as regulators of differentiation and cell fate decisions. Cell Stem Cell, 2010, 7(1), 36-41.
[http://dx.doi.org/10.1016/j.stem.2010.06.012] [PMID: 20621048]
[14]
Singh, Y.; Garden, O.A.; Lang, F.; Cobb, B.S. MicroRNA-15b/16 enhances the induction of regulatory T Cells by regulating the expression of rictor and mTOR. J. Immunol., 2015, 195(12), 5667-5677.
[http://dx.doi.org/10.4049/jimmunol.1401875] [PMID: 26538392]
[15]
Byun, J-S.; Hong, S-H.; Choi, J-K.; Jung, J-K.; Lee, H-J. Diagnostic profiling of salivary exosomal microRNAs in oral lichen planus patients. Oral Dis., 2015, 21(8), 987-993.
[http://dx.doi.org/10.1111/odi.12374] [PMID: 26389700]
[16]
Momen-Heravi, F.; Trachtenberg, A.J.J.; Kuo, W.P.P.; Cheng, Y.S.S. Genomewide study of salivary microRNAs for detection of oral cancer. J. Dent. Res., 2014, 93(7)(Suppl.), 86S-93S.
[http://dx.doi.org/10.1177/0022034514531018] [PMID: 24718111]
[17]
Roy, R.; Singh, R.; Chattopadhyay, E.; Ray, A.; Sarkar, N.; Aich, R.; Paul, R.R.; Pal, M.; Roy, B. MicroRNA and target gene expression based clustering of oral cancer, precancer and normal tissues. Gene, 2016, 593(1), 58-63.
[http://dx.doi.org/10.1016/j.gene.2016.08.011] [PMID: 27515006]
[18]
Ma, H.; Wu, Y.; Yang, H.; Liu, J.; Dan, H.; Zeng, X.; Zhou, Y.; Jiang, L.; Chen, Q. MicroRNAs in oral lichen planus and potential miRNA-mRNA pathogenesis with essential cytokines: a review. Oral Surg. Oral Med. Oral Pathol. Oral Radiol., 2016, 122(2), 164-173.
[http://dx.doi.org/10.1016/j.oooo.2016.03.018] [PMID: 27282956]
[19]
Peng, Q.; Zhang, J.; Zhou, G. Differentially circulating exosomal microRNAs expression profiling in oral lichen planus. Am. J. Transl. Res., 2018, 10(9), 2848-2858.
[PMID: 30323871]
[20]
Michael, A.; Bajracharya, S.D.; Yuen, P.S.T.; Zhou, H.; Star, R.A.; Illei, G.G.; Alevizos, I. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis., 2010, 16(1), 34-38.
[http://dx.doi.org/10.1111/j.1601-0825.2009.01604.x] [PMID: 19627513]
[21]
Yoshizawa, J.M.; Wong, D.T.W. Salivary microRNAs and oral cancer detection. Methods Mol. Biol., 2013, 936, 313-324.
[http://dx.doi.org/10.1007/978-1-62703-083-0_24] [PMID: 23007518]
[22]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[23]
Chen, J.; Tran, U.M.; Rajarajacholan, U.; Thalappilly, S.; Riabowol, K. ING1b-inducible microRNA203 inhibits cell proliferation. Br. J. Cancer, 2013, 108(5), 1143-1148.
[http://dx.doi.org/10.1038/bjc.2013.50] [PMID: 23462723]
[24]
Liu, Q.; Wang, X.; Liu, Y.; Wei, M.; Chen, L. A combinative analysis of gene expression profiles and microRNA expression profiles identifies critical genes and microRNAs in oral lichen planus. Arch. Oral Biol., 2016, 68, 61-65.
[http://dx.doi.org/10.1016/j.archoralbio.2016.03.018] [PMID: 27100321]
[25]
Nylander, E.; Ebrahimi, M.; Wahlin, Y-B.; Boldrup, L.; Nylander, K. Changes in miRNA expression in sera and correlation to duration of disease in patients with multifocal mucosal lichen planus. J. Oral Pathol. Med., 2012, 41(1), 86-89.
[http://dx.doi.org/10.1111/j.1600-0714.2011.01063.x] [PMID: 21777290]
[26]
Hildebrand, J.; Rütze, M.; Walz, N.; Gallinat, S.; Wenck, H.; Deppert, W.; Grundhoff, A.; Knott, A. A comprehensive analysis of microRNA expression during human keratinocyte differentiation in vitro and in vivo. J. Invest. Dermatol., 2011, 131(1), 20-29.
[http://dx.doi.org/10.1038/jid.2010.268] [PMID: 20827281]
[27]
Arantes, L.M.R.B.; Laus, A.C.; Melendez, M.E.; de Carvalho, A.C.; Sorroche, B.P.; De Marchi, P.R.M.; Evangelista, A.F.; Scapulatempo-Neto, C.; de Souza Viana, L.; Carvalho, A.L. MiR-21 as prognostic biomarker in head and neck squamous cell carcinoma patients undergoing an organ preservation protocol. Oncotarget, 2017, 8(6), 9911-9921.
[http://dx.doi.org/10.18632/oncotarget.14253] [PMID: 28039483]
[28]
Zheng, Z.; Qu, J-Q.; Yi, H-M.; Ye, X.; Huang, W.; Xiao, T.; Li, J-Y.; Wang, Y-Y.; Feng, J.; Zhu, J-F.; Lu, S-S.; Yi, H.; Xiao, Z-Q. MiR-125b regulates proliferation and apoptosis of nasopharyngeal carcinoma by targeting A20/NF-κB signaling pathway. Cell Death Dis., 2017, 8(6)e2855
[http://dx.doi.org/10.1038/cddis.2017.211] [PMID: 28569771]
[29]
Tang, X.; Tang, R.; Xu, Y.; Wang, Q.; Hou, Y.; Shen, S.; Wang, T. MicroRNA networks in regulatory T cells. J. Physiol. Biochem., 2014, 70(3), 869-875.
[http://dx.doi.org/10.1007/s13105-014-0348-x] [PMID: 25108555]
[30]
Chen, J.; Du, G.; Chang, Y.; Wang, Y.; Shi, L.; Mi, J.; Tang, G. Downregulated MiR-27b promotes keratinocyte proliferation by targeting PLK2 in oral lichen planus. J. Oral Pathol. Med., 2019, 48(4), 326-334.
[http://dx.doi.org/10.1111/jop.12826]
[31]
Aghbari, S.M.H.; Gaafar, S.M.; Shaker, O.G.; Ashiry, S.E.; Zayed, S.O. Evaluating the accuracy of microRNA27b and microRNA137 as biomarkers of activity and potential malignant transformation in oral lichen planus patients. Arch. Dermatol. Res., 2018, 310(3), 209-220.
[http://dx.doi.org/10.1007/s00403-018-1805-0] [PMID: 29368136]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 31
Year: 2019
Page: [2816 - 2823]
Pages: 8
DOI: 10.2174/1568026619666191121144407
Price: $65

Article Metrics

PDF: 23
HTML: 4