title: MicroRNA expression profiling and functional annotation analysis of their targets associated with the malignant transformation of oral leukoplakia.
abstract: In spite the tremendous achievements that have been acquired in the field of molecular biology, the underlying mechanism associated with malignant transformed oral leukoplakia (OLK) is still unclear and poorly understood. The aim of this study is to investigate the microRNA (miRNA) expression profiles in OLK and its aggressive transformed tissues from the white lesion of human oral mucosa. The original miRNA expression dataset was downloaded from Gene Expression Omnibus (GEO) database and differentially expressed miRNAs were identified using two-sample t test method. Unsupervised hierarchical clustering and principal component analysis of these differentially expressed miRNAs indicated that 38-miRNA candidates could significantly discriminate OLK from malignant transformed oral mucosa samples. Besides, potential transcription factors were predicted using CyTargetLinker plugin and the miRNA-mRNA regulatory network associated with the malignant pathogenesis was visualized in Cytoscape environment. Totally, 3-miRNA signatures (miR-129-5p, miR-339-5p and miR-31*) were found to be hubs that mediated the initiation and progression of OLK from the non-malignant to the aggressive one via targeting various transcription factors. Functional enrichment analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that the dysregulation of immune response was responsible for oral carcinogenesis. In conclusion, we constructed a miRNA-mRNA regulatory network associated with the malignant transformation of OLK, and screened out some miRNAs and transcription factors that may have prominent roles during OLK malignant progression.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: akpar15@163.com.
authors.forename: Aikebaier
authors.initials: A
authors.lastname: Maimaiti
authors.affiliation: Xinjiang Uyghur Medical School, Hetian 848000, China. Electronic address: kaiserrena86@aliyun.com.
authors.forename: Kaisaier
authors.initials: K
authors.lastname: Abudoukeremu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: tielu@bjmu.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Tie
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: pannay26@bjmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: xjli@bjmu.edu.cn.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Li
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016000:Cluster Analysis; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis
chemical_list: D035683:MicroRNAs
keywords: Expression profiles; Malignant transformation; MicroRNA microarray; Oral leukoplakia