Overlapping Region of p53/Wrap53 Transcripts: Mutational Analysis and Sequence Similarity with microRNA-4732-5p

Abstract

Background: Although the majority of investigations concerned with TP53 and its protein have focused on coding regions, recently a set of studies highlighted significant roles of regulatory elements located in p53 mRNA, especially 5´ UTR. The wrap53α transcript is one of those that acts as a natural antisense agent, forming RNA-RNA hybrids with p53 mRNA and protecting it from degradation. Materials and Methods: In this study, we focused on the mutation status of exon 1α of the WRAP53 gene (according to exon 1 of p53) in 160 breast tumor tissue samples and conducted a bioinformatics search for probable miRNA binding site in the p53/wrap53 overlapping region. Mutations were detected, using single stranded conformation polymorphism (SSCP) and sequencing. We applied the miRBase database for prediction of miRNAs which target overlapping region of p53/wrap53 transcripts. Results: Our results showed all samples to have wild type alleles in exon 1 of TP53 gene. We could detect a novel and unreported intronic mutation (IVS1+56, G>C) outside overlapping regions of p53/wrap53 genes in breast cancer tissues and also predict the presence of a binding site for miR-4732-5p in the 5´ UTR of Wrap53 mRNA. Conclusions: From our findings we propose designing further studies focused on overexpression of miRNA-4732-5p and introducing different mutations in the overlapping region of wrap53 and p53 genes in order to study their effects on p53 and its ΔN isoform (Δ40p53) expression. The results may provide new pieces in the p53 targeting puzzle for cancer therapy.

Changes in the Expression of Circulating microRNAs in Systemic Lupus Erythematosus Patient Blood Plasma After Passing Through a Plasma Adsorption Membrane

“…The fact that miR‐1246 was reduced after passing through the immunoadsorption column could contribute to this improving in some way, but clinical significance is still unknown. Next, miR‐4732‐5p shares sequence similarity with tumor suppressor gene p53 , and the fact that miR‐4732‐5p was reduced after passing through the immunoadsorption column is worth considering. The sequence of mir‐6088 has been identified, its target and physiological significance is still unknown.…”

Possible tumor suppressive role of the miR-144/451 cluster in esophageal carcinoma as determined by principal component regression analysis

“…A study by Matsushita et al (44) demonstrated that miR-144-5p targets CCNE1/2 directly to suppress the proliferation of bladder cancer cells. The miR-4732-3p and miR-4732-5p members of the miR-144/451 cluster were identified after the other members, and therefore, few studies currently exist about these miRNAs (45,46). Omura et al (45) suggested that miR-4732-5p may facilitate the prediction of disease recurrence following S-1 chemotherapy treatment through mutational analysis and sequence similarity.…”

“…Omura et al (45) suggested that miR-4732-5p may facilitate the prediction of disease recurrence following S-1 chemotherapy treatment through mutational analysis and sequence similarity. Furthermore, Pouladi et al (46) demonstrated that, by binding with the 5'-untranslated region of WRAP53, hsa-miR-4732-5p promoted breast cancer progression. Ultimately, these studies provide evidence demonstrating that members of the miR-144/451 cluster appear to serve important roles in multiple biological pathways, and that individual miRNAs of the miR-144/451 cluster may function as part of different biological pathways in different types of tissues.…”

Lack of Association of Intron 3 16 bp Polymorphism of TP53 with Breast Cancer among Iranian-Azeri Patients

“…tumor could significantly affect the prognosis of patients and response to treatment (Farnebo et al, 2010;Pouladi et al, 2013). Several polymorphisms have been identified in coding and noncoding regions of p53 that some of them have been associated with increased risk of cancer (Whibley et al, 2009).…”