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Adverse effect of miRNA function induced by single nucleotide polymorphism on the occurrence of uveal melanoma
Fatemeh Eskandari,1Pegah Javid,2Mansoureh Azadeh,3,*
1. Zist Fanavari Novin biotechnology institute 2. Zist Fanavari Novin biotechnology institute 3. Zist Fanavari Novin biotechnology institute
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Introduction: The ocular and adnexal structures comprise approximately 5 % of all melanomas. Around 95% of ocular melanomas are uveal in origin, whereas primary conjunctival and orbital melanoma are very rare. Uveal melanoma is the most common primary intraocular malignant tumour. In the current study, we have researched the negative effect of a common single nucleotide polymorphism (SNP: rs1222227623) while converting A to G at the seed match of miR-27a-3p to 3'UTR sequence of PATZ1 gene. The PATZ1 (POZ/BTB and AT Hook Containing Zinc Finger 1) is a Protein Coding gene involved in Androgen receptor signalling and Co-regulation of Androgen receptor activity pathways.
Methods: For this purpose, GSE27831 selected from GEO dataset microarray studies was used to obtain the top differentially expressed genes though uveal melanoma. The David Database was used to cluster genes and identify the ones involved in the transcriptional regulatory pathway in cancer, including the PATZ1 gene. The relationship between studied miRNA and SNP was shown in miRNASNP-v3 database.
Results: The results showed that the miR-27a-3p blocks gene's expression, and acts as a tumour suppressor in uveal melanoma by binding to the 3'UTR region of PATZ1 gene. The occurrence of rs1222227623 (A/G on chr19:13836466) at the seed match of miR-27a-3p to PATZ1 made the binding to be lost. It makes the gene not to be under the control of miRNA anymore and upregulation will occur in gene.
Conclusion: Thus, our data suggest that rs1222227623 could be a disease-associated SNP (dSNP). It is a common polymorphism in miR-27a-3p, which affects the regulation of PATZ1 gene and results in the genetic predisposition to uveal melanoma. Its role in tumour genesis through somatic mutation preliminary evidence suggests that these effects are mediated through target genes which expressions are affected by the SNP status.
