p53 plays a critical role in regulating cell-cycle progression and in maintaining genomic integrity when cells sustain DNA damage. The p53 protein functions as a nuclear transcription factor that regulates expression of various genes encoding proteins involved in cell-cycle checkpoints (e.g., p21WAF1/CIP1), apoptosis, and DNA repair .Since its important role in many cellular processes, p53 is prone to mutations and is mutated in 80–90% of NSCLCs and in 50% of SCLCs [Sekido et al., 2001]. Most missense mutations in the TP53 gene occur in the DNA-binding domain, abolishing its transactivation function because mutant p53 cannot activate p21WAF1/CIP1, the cell cycle can proceed unabated. It is Exon 5-8 which are very prone to mutations & codon 157 is commonly known as mutational hotspot in lung Cancers, besides that codon 248 & 273 mutations are hotspot positions in other cancers for example, colon and liver cancer, suggesting the heterogeneity among TP53 mutations. One interesting thing is these codons contain CpG islands, and the presence of 5-methyl cytosine greatly enhances binding of a major cigarette smoke carcinogen, benzo[a] pyrene, diol epoxide to guanine, such that benzo[a]pyrene, diol epoxide selectively forms adducts at TP53 hot spots [Denissenko et al., …show more content…
elegans [54]. However, 3- untranslated region (3-UTR) of target messenger RNAs silences their target genes causing either degradation or inhibition of translation. Its biogenesis involves the transcription of pri-miRNA and this is mediated by a very important polymerase RNA POL-Ⅱ [55] although a small group of microRNA can be transcribed by RNA POL-Ⅲ[56].In nucleus pri-microRNA is processed by RNase Ⅲ enzyme Drosha and the protein Pasha/DGCR8 into pre-miRNAs [57]. In second processing step within cytoplasm a small dsRNA structure having 22 nucleotides in length is excised from pre-miRNA hairpin by aenother RNase Ⅲ enzyme, Dicer [58, 59]. Finally the mature single-stranded microRNA is loaded into the RNA-induced silencing complex (RISC), which mediates the degradation or translation inhibition of target mRNA by binding to its seed sequence in the target mRNA’s 3’-UTR. Since lung cancer remains prime concern about cancer-related death worldwide [Takamizawa et al, Res 2004; 64: 3753-3756.] were first to link micro RNA expression to lung cancer. Since then there have been large number of studies relating microRNA expression with lung cancer. They describe the roles of microRNAs as supressing tumours and Oncogenes and their role in prognosis and diagnosis of lung cancer. Studies have shown that micro RNAs, whose expression is altered in many tumours, may function as a novel class of oncogenes