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Objective: Constituents of tobacco can cause DNA adduct formation and are implicated in the development of oral squamous cell carcinoma (OSCC). However, there are few published studies on the mechanism(s) that underlie tobacco-associated oral carcinogenesis. It is widely known that microRNAs have an important role in the regulation of tumor generation and development. The purpose of this study was to investigate the changes of miRNAs and mRNAs expression and mutual relationship of regulation in the process of 4-nitroquinoline 1-oxide-induced carcinogenesis. Methods: 4-nitroquinoline-1-oxide (4NQO) was used to induce tongue cancer in SD rats. The differentially expressed miRNAs and mRNAs were screened using miRNA and mRNA chip technique. The differentially expressed miRNAs and mRNAs were verified by RT-PCR followed by gene ontology (GO) analysis in an attempt to build the miRNA-gene correlation network and the miRNA-go-network using bioinformatics technology. Results: The results indicated that 57 miRNAs and 474 mRNA/EST transcripts exhibited differential expression profiles between tumor and normal tongue tissues. In tumor tissue, the expression levels of the members of the rno-miR-30 family (rno-miR-30a, -30a*, -30b-5p, -30c, -30d, -30e and -30e*) were only 8% to 37% of their counterparts in the control group. Three members of the rno-miR-30 family (rno-miR-30a*, -30d, and -30e*) were the three highest degrees of miRNAs based on the miRNA-gene networks, and members rno-miR-30 b-5p, -30c, -30d, and -30e were four of the highest degrees of miRNAs uncovered by miRNA-go-network. The maximum-enrichment GOs targeted by the differentially expressed miRNA-30 family include forward locomotion, striated muscle cell development, ADP transport, and the beta-alanine catabolic process. Conclusion: These data clearly showed that decreased expression of the rno-miR-30 family may play a crucial role in carcinogenesis development, especially in metabolic processes and cell movement. Further investigations are needed to understand the role of the miR-30 family regulatory mechanism during the development of OSCC.) |
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Keywords:Oncology; oral squamous cell carcinoma; miRNAs; microarray; bioinformatics; pathway |
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