The Effect of a Single Nucleotide Polymorphism on a miRNA Function in the Papillary Thyroid Carcinoma (PTC)

Papillary Thyroid carcinoma (PTC) is the most common form of well-differentiated thyroid cancer, and themost common form of thyroid cancer to result from radiation exposure. PTC has shown strong heritabilityand no predisposing mutations in the germ-line. In the current study, we have researched the effect ofcommon T/G polymorphism (rs۱۳۵۷۸۶۶۳۹۲) as an SNP on the miR-۳۴a-۳p sequence and its binding to themRNA sequence of MET proto-oncogene, receptor tyrosine kinase gene (MET) (ENSG۰۰۰۰۰۱۰۵۹۷۶.۱۴) inPTC through bioinformatics. The MET gene encodes a member of the tyrosine kinase receptor family ofproteins and the MET proto-oncogene product. For this purpose, GEO datasets showed the top ۲۵۰differentially expressed genes. The David database was used to cluster the gens and it revealed the involvedgenes in transcriptional misregulation pathway in cancer including MET gene. The miRNASNP-v۳ databaseshowed the relationship between studied miRNA and SNP. The results showed that binding to the ۳’UTRregion of MET, the miR-۳۴a-۳p blocks gene’s expression, and acts as a tumour suppressor in PTC. Theoccurrence of rs۱۳۵۷۸۶۶۳۹۲ (T/G on chr۱:۹۱۵۱۷۰۹) in the seed match of miR-۳۴a-۳p (chr۱:۹۱۵۱۷۰۸-۹۱۵۱۷۱۴) and MET (chr۷:۱۱۶۷۹۶۱۲۴-۱۱۶۷۹۸۳۸۶), made the binding to be lost. It makes the gene not to beunder the control of miRNA anymore and upregulation will occur. Thus, our data suggest that rs۱۳۵۷۸۶۶۳۹۲is a disease-associated SNP since as a common polymorphism in miR-۳۴a-۳p affects the regulation of theMET gene and result in the genetic predisposition to PTC. Its role in the tumorigenesis through somaticmutation Preliminary evidence suggests that these effects are mediated through target genes whichexpressions are affected by the SNP status.

کلیدواژه ها:

PTC ، MET gene ، miR-۳۴a-۳p ، rs۱۳۵۷۸۶۶۳۹۲