Citation Information :
Kumaraguru M, Doraikannan S, Jayaseelan V, Indiran MA, Venkadessan K. Deciphering the MicroRNA Targets of Candidate Genes in Oral Submucous Fibrosis: A Computational Approach. World J Dent 2024; 15 (6):531-538.
Introduction: Oral submucous fibrosis (OSMF) is an oral premalignant disorder marked by inflammation of the submucosal tissues, leading to progressive fibrosis and ultimately resulting in rigidity and limited mouth opening. Literature has indicated that a multitude of microRNA (miRNAs) are abnormally expressed in OSMF, and this dysregulation may play a role in the condition's diagnosis, prognosis, and therapeutic aspects.
Aim: The aim of this study was to identify miRNA targets of candidate genes in OSMF using a computational approach.
Materials and methods: The Gene Expression Omnibus (GEO) software was used to obtain data on differentially expressed genes for OSMF without dysplasia (OSMWT), OSMF with dysplasia (OSMWD), and OSMF with squamous cell carcinoma (OSCC). The genes that were common to OSMWT, OSMWD, and OSCC were further subjected to analysis by miRNA Target Prediction Database (miRDB) software to identify the miRNAs that targeted the candidate genes.
Results: This study yielded 63 miRNAs with a target score of 90–100 and potentially associated with OSMF. The miRNAs hsa-miR-5011-5p and hsa-miR-8087 had the highest target score of 100. This was followed by hsa-miR-520d-5p, hsa-miR-524-5p, hsa-miR-7162-3p, hsa-miR-499a-5p, hsa-miR-1324, and hsa-miR-520d-5p with a target score of 99.
Conclusion: This study has aided in the process of gene and miRNA prioritization in the context of OSMF, which can serve as a useful tool for understanding the disease.
Clinical significance: The findings of this study can serve as the basis for formulating appropriate pharmacotherapy for OSMF along the lines of personalized medicine.
Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1966;22(6):764–779. DOI: 10.1016/0030-4220(66)90367-7
Rao NR, Villa A, More CB, et al. Oral submucous fibrosis: a contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management. J Otolaryngol Head Neck Surg 2020;49(1):3. DOI: 10.1186/s40463-020-0399-7
Cox SC, Walker DM. Oral submucous fibrosis. A review. Aust Dent J 1996;41(5):294–299. DOI: 10.1111/j.1834-7819.1996.tb03136.x
Heck JE, Marcotte EL, Argos M, et al. Betel quid chewing in rural Bangladesh: prevalence, predictors and relationship to blood pressure. Int J Epidemiol 2012;41(2):462–471. DOI: 10.1093/ije/dyr191
Frohwitter G, Buerger H, Korsching E, et al. Site-specific gene expression patterns in oral cancer. Head Face Med 2017;13(1):6. DOI: 10.1186/s13005-017-0138-0
Smolarz B, Durczyński A, Romanowicz H, et al. MiRNAs in cancer (review of literature). Int J Mol Sci 2022;23(5). DOI: 10.3390/ijms23052805
Gassling V, Hampe J, Açil Y, et al. Disease-associated miRNA-mRNA networks in oral lichen planus. PLoS One 2013;8(5):e63015. DOI: 10.1371/journal.pone.0063015
Lu J, Clark AG. Impact of microRNA regulation on variation in human gene expression. Genome Res 2012;22(7):1243–1254. DOI: 10.1101/gr.132514.111
Yang JS, Lai EC. Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol Cell 2011;43(6):892–903. DOI: 10.1016/j.molcel.2011.07.024
Jishnu PV, Shenoy SU, Sharma M, et al. Comprehensive analysis of microRNAs and their target genes in oral submucous fibrosis. Oral Dis 2023;29(5):1894–1904. DOI: 10.1111/odi.14219
Hsieh PL, Chen SH, Huang YF, et al. The functional roles of microRNAs in the pathogenesis of oral submucous fibrosis. J Dent Sci 2022;17(2):683–687. DOI: 10.1016/j.jds.2021.07.008
Liao YW, Yu CC, Hsieh PL, et al. miR-200b ameliorates myofibroblast transdifferentiation in precancerous oral submucous fibrosis through targeting ZEB2. J Cell Mol Med 2018;22(9):4130–4138. DOI: 10.1111/jcmm.13690
Xie B, Agam G, Balasubramanian S, et al. Disease gene prioritization using network and feature. J Comput Biol 2015;22(4):313–323. DOI: 10.1089/cmb.2015.0001
Clough E, Barrett T. The Gene Expression Omnibus database. Methods Mol Biol 2016;1418:93–110. DOI: 10.1007/978-1-4939-3578-9_5
Chen J, Liu B, Xie X, et al. Comparative molecular analysis of oral submucous fibrosis and other organ fibrosis based on weighted gene co-expression network analysis. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2022;47(12):1663–1672. DOI: 10.11817/j.issn.1672-7347.2022.220452
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014;15(12):550. DOI: 10.1186/s13059-014-0550-8
Sterck L. Draw Venn Diagram. Available from: https://bioinformatics.psb.ugent.be/webtools/Venn/
Wang X. miRDB: a microRNA target prediction and functional annotation database with a wiki interface. RNA 2008;14(6):1012–1017. DOI: 10.1261/rna.965408
Cheng RH, Wang YP, Chang JY, et al. Genetic susceptibility and protein expression of extracellular matrix turnover-related genes in oral submucous fibrosis. Int J Mol Sci 2020;21(21). DOI: 10.3390/ijms21218104
Rajendran R, Vidyarani. Familial occurrence of oral submucous fibrosis: report of eight families from northern Kerala, South India. Indian J Dent Res 2004;15(4):139–144. PMID: 16035643.
Wollina U, Verma SB, Ali FM, et al. Oral submucous fibrosis: an update. Clin Cosmet Investig Dermatol 2015;8:193–204. DOI: 10.2147/CCID.S80576
Chanjiao Y, Chunyan C, Xiaoxin Q, et al. MicroRNA-378a-3p contributes to ovarian cancer progression through downregulating PDIA4. Immun Inflamm Dis 2021;9(1):108–119. DOI: 10.1002/iid3.350
Gao C, Zhou C, Zhuang J, et al. MicroRNA expression in cervical cancer: novel diagnostic and prognostic biomarkers. J Cell Biochem 2018;119(8):7080–7090. DOI: 10.1002/jcb.27029
Liang G, Meng W, Huang X, et al. miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer. Proc Natl Acad Sci U S A 2020;117(8):4347–4357. DOI: 10.1073/pnas.1917531117
Wang C, Shi Z, Hong Z, et al. Microrna-1276 promotes colon cancer cell proliferation by negatively regulating LACTB. Cancer Manag Res 2020;12:12185–12195. DOI: 10.2147/CMAR.S278566
Gao S, Shi P, Tian Z, et al. Overexpression of miR-1225 promotes the progression of breast cancer, resulting in poor prognosis. Clin Exp Med 2021;21(2):287–296. DOI: 10.1007/s10238-020-00676-7
Wang L, Chen Y, Yan Y, et al. miR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT. Front Oncol 2020;10:585976. DOI: 10.3389/fonc.2020.585976
Jia B, Zhang S, Wu S, et al. MiR-770 promotes oral squamous cell carcinoma migration and invasion by regulating the Sirt7/Smad4 pathway. IUBMB Life 2021;73(1):264–272. DOI: 10.1002/iub.2426
Prasad SR, Pai A, Shyamala K, et al. EXpression of salivary miRNA 21 in oral submucous fibrosis (OSMF): an observational study. Microrna 2020;9(4):295–302. DOI: 10.2174/2211536609666200127143749
Cervigne NK, Reis PP, Machado J, et al. Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Hum Mol Genet 2009;18(24):4818–4829. DOI: 10.1093/hmg/ddp446
Zahran F, Ghalwash D, Shaker O, et al. Salivary microRNAs in oral cancer. Oral Dis 2015;21(6):739–747. DOI: 10.1111/odi.12340
Singh P, Srivastava AN, Sharma R, et al. Circulating MicroRNA-21 expression as a novel serum biomarker for oral sub-mucous fibrosis and oral squamous cell carcinoma. Asian Pac J Cancer Prev 2018;19(4):1053–1057. DOI: 10.22034/APJCP.2018.19.4.1053
Mohanan EM, Jhala D, More CB, et al. Bioinformatics analysis of miRNA and its associated genes to identify potential biomarkers of oral submucous fibrosis and oral malignancy. Cancer Rep (Hoboken) 2023;6(4):e1787. DOI: 10.1002/cnr2.1787
Lajer CB, Nielsen FC, Friis-Hansen L, et al. Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study. Br J Cancer 2011;104(5):830–840. DOI: 10.1038/bjc.2011.29
Jin T, Zhang Y, Zhang T. miR-524-5p suppresses migration, invasion, and EMT progression in breast cancer cells through targeting FSTL1. Cancer Biother Radiopharm 2020;35(10):789–801. DOI: 10.1089/cbr.2019.3046
Wang Y, Liu S, Lv F, et al. hsa-miR-216a-3p regulates cell proliferation in oral cancer via the Wnt3a/β-catenin pathway. Mol Med Rep 2023;27(6). DOI: 10.3892/mmr.2023.13015
Adhami M, MotieGhader H, Haghdoost AA, et al. Gene co-expression network approach for predicting prognostic microRNA biomarkers in different subtypes of breast cancer. Genomics 2020;112(1):135–143. DOI: 10.1016/j.ygeno.2019.01.010
Tsukerman P, Yamin R, Seidel E, et al. miR-520d-5p directly targets TWIST1 and downregulates the metastamiR miR-10b. Oncotarget 2014;5(23):12141–12150. DOI: 10.18632/oncotarget.2559
Liu J, Huang L, Su P, et al. MicroRNA-499a-5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling. Oncol Lett 2018;15(4):4113–4120. DOI: 10.3892/ol.2018.7814
Urbanek-Trzeciak MO, Galka-Marciniak P, Nawrocka PM, et al. Pan-cancer analysis of somatic mutations in miRNA genes. EBioMedicine 2020;61:103051. DOI: 10.1016/j.ebiom.2020.103051
Griffiths-Jones S, Grocock RJ, van Dongen S, et al. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006;34(Database issue):D140–D144. DOI: 10.1093/nar/gkj112