BACKGROUND: Oral squamous cell carcinoma (OSCC) severely affects the quality of life and the 5-year survival rate is low. Exploring the potential miRNA-mRNA regulatory network and analyzing hub genes and clinical data can provide a theoretical basis for further elucidating the pathogenesis of OSCC. METHODS: The miRNA expression datasets of GSE113956 and GSE124566 and mRNA expression datasets of GSE31056, GSE37991 and GSE13601 were obtained from the Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were screened using GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. The PPI network was established through STRING database and the hub genes were preliminarily screened out by Cytoscape software. After identifying the hub genes in the TCGA database, we predicted the potential DEM transcription factors, constructed a miRNA-mRNA regulatory network, and analyzed the relationship between the hub genes and clinical data. RESULTS: A total of 28 DEMs and 764 DEGs were screened out, which were composed of 285 up-regulated genes and 479 down-regulated genes. Enrichment analysis showed that up-regulation of DEGs were mainly enriched in extracellular matrix organization and cancer-related pathway, while down-regulation of DEGs were mainly enriched in muscular system process and adrenaline signal transduction. After preliminary screening by PPI network and identification in TCGA, the up-regulated FN1, COL1A1, COL1A2, AURKA, CCNB1, CCNA2, SPP1, CDC6, and down-regulated ACTN2, TTN, IGF1, CAV3, MYL2, DMD, LDB3, CSRP3, ACTA1, PPARG were identified as hub genes. The miRNA-mRNA regulation network showed that hsa-miR-513b was the DEM with the most regulation, and COL1A1 was the DEG with the most regulation. In addition, CDC6, AURKA, CCNB1 and CCNA2 were related to overall survival and tumor differentiation. CONCLUSIONS: The regulatory relationship of hsa-miR-513b/ CDC6, CCNB1, CCNA2 and the regulatory relationship of hsa-miR-342-5p /AURKA were not only verified in the miRNA-mRNA regulatory network but also related to overall survival and tumor differentiation. These results indicated that they participated in the cellular regulatory process, and provided a molecular mechanism model for the study of pathogenesis.

• MeSH
• Epinephrine MeSH
• Aurora Kinase A genetics   metabolism   MeSH
• Squamous Cell Carcinoma of Head and Neck * genetics   MeSH
• Gene Regulatory Networks MeSH
• Quality of Life MeSH
• Humans MeSH
• RNA, Messenger genetics   metabolism   MeSH
• MicroRNAs * genetics   MeSH
• Mouth Neoplasms * genetics   MeSH
• PPAR gamma genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Gene Expression Profiling MeSH
• Transcription Factors genetics   MeSH
• Computational Biology methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Selective inhibitors of kinases that regulate the cell cycle, such as cyclin-dependent kinases (CDKs) and aurora kinases, could potentially become powerful tools for the treatment of cancer. We prepared and studied a series of 3,5,7-trisubstituted pyrazolo[4,3-d]pyrimidines, a new CDK inhibitor scaffold, to assess their CDK2 inhibitory and antiproliferative activities. A new compound, 2i, which preferentially inhibits CDK2, CDK5, and aurora A was identified. Both biochemical and cellular assays indicated that treatment with compound 2i caused the downregulation of cyclins A and B, the dephosphorylation of histone H3 at Ser10, and the induction of mitochondrial apoptosis in the HCT-116 colon cancer cell line. It also reduced migration as well as tube and lamellipodia formation in human endothelial cells. The kinase inhibitory profile of compound 2i suggests that its anti-angiogenic activity is linked to CDK5 inhibition. This dual mode of action involving apoptosis induction in cancer cells and the blocking of angiogenesis-like activity in endothelial cells offers possible therapeutic potential.

• MeSH
• Apoptosis drug effects   MeSH
• Aurora Kinase A antagonists & inhibitors   MeSH
• Cell Cycle drug effects   MeSH
• Cyclin-Dependent Kinase 2 antagonists & inhibitors   MeSH
• Cyclin-Dependent Kinase 5 antagonists & inhibitors   MeSH
• Human Umbilical Vein Endothelial Cells MeSH
• HCT116 Cells MeSH
• Cyclin-Dependent Kinase Inhibitor Proteins chemical synthesis   chemistry   pharmacology   MeSH
• Angiogenesis Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Protein Kinase Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Humans MeSH
• Antineoplastic Agents chemical synthesis   chemistry   pharmacology   MeSH
• Drug Design MeSH
• Drug Screening Assays, Antitumor MeSH
• Molecular Docking Simulation MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH