The role of p19 and p21 H-Ras proteins and mutants in miRNA expression in cancer and a Costello syndrome cell model

摘要: P19 H-Ras, a second product derived from the H-Ras gene by alternative splicing, induces G1/S phase delay, thereby maintaining cells in reversible quiescence state. When P21 is mutated tumour cells, protein also mutated. The mutation Q61L frequently detected different tumours, which acts as constitutive activator of Ras functions and considered to be strong activating mutant. Additionally, rare congenital disorder named Costello Syndrome, described children, mainly due G12S p19 p21 proteins, present 90 % Syndrome patients. Our aim better understand role proteins cancer development, concerning miRNAs expression. Total expression regulated were first analyzed human miRNA microarrays assays. Previously selected miRNAs, further developed cell lines containing mutants, that included mutant, with PCR Real-Time Taq Man Assays primers. This study describes how affects RNA world shows that: i) miR-342, miR-206, miR-330, miR-138 miR-99b are upregulated but not p19W164A mutant; ii) anti-miR-206 can restore G2 presence p19; iii) p21Q61L regulate their own splicing; iv) miR-206 differentially v) P19G12S mutants show clear upregulation miR-374, miR-126, miR-335 let-7. These results allow us conclude plays an important open up new line consequences this on syndrome. Furthermore, they suggest oncogenes may have sufficiently impact promote development numerous cancers.