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The role of microRNAs as oncogenes and tumor suppressor genes has emerged in several cancers, including hepatocellular carcinoma (HCC). The pivotal tumor suppressive role of p53-axis is indicated by the presence of inactivating mutations in TP53 gene in nearly all cancers. A close interaction between these two players, as well as the establishment of complex p53/miRNAs loops demonstrated the strong contribution of p53-effector miRNAs in enhancing the p53-mediated tumor suppression program. On the other hand, the direct and indirect targeting of p53, as well as the regulation of its stability and activity by specific microRNAs, underlie the importance of the fine-tuning of p53 pathway, affecting the cell fate of damaged/transformed cells. The promising results of miRNAs-based therapeutic approaches in preclinical studies and their entrance in clinical trials demonstrate the feasibility of this strategy in several diseases, including cancer. Molecularly targeted drugs approved so far for HCC treatment show intrinsic or acquired resistances with disease progression in many cases, therefore the identification of effective and non-toxic agents for the treatment of HCC is actually an unmet clinical need. The knowledge of p53/miRNA inter-relations in HCC may provide useful elements for the identification of novel combined approaches in the context of the "personalized-medicine" era.
Pubmed ID: 27918441
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The IARC TP53 Mutation Database compiles all TP53 gene variations identified in human populations and tumor samples. Data are compiled from the peer-reviewed literature and from generalist databases. The following datasets are available: # TP53 somatic mutations in sporadic cancers # TP53 germline mutation in familial cancers # Common TP53 polymorphisms identified in human populations # Functional and structural properties of P53 mutant proteins # TP53 gene status in human cell-lines # Mouse-models with engineered TP53 The database includes various annotations on the predicted or experimentally assessed functional impact of mutations, clinicopathologic characteristics of tumors and demographic and life-style information on patients. The database is meant to be a source of information on TP53 mutations for a broad range of scientists and clinicians who work in different research areas: # Basic research, to study the structural and functional aspects of the p53 protein # Molecular pathology of cancer, to understand the clinical significance of mutations identified in cancer patients # Molecular epidemiology of cancer, to analyze the links between specific exposures and mutation patterns and to make inferences about possible causes of cancer # Molecular genetics, to analyze genotype/phenotype relationships
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