rs6426881 in the 3'-UTR of PBX1 is involved in breast and gastric cancers via altering the binding potential of miR-522-3p

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Abstract
Background Breast and gastric cancers are the most important diseases that lead to cancer death and social healthcare challenge. Overexpression of PBX1, a proto-oncogene, is correlated with the progression and metastasis of various cancers. For the first time, in this study the researchers evaluated the relationship between rs6426881, affecting miR-522-3p binding to the PBX1, with breast and gastric cancers. Methods and results The Microarray analysis was performed for finding the relative expression level of PBX1 and hsa-miR-522-3p, based on high throughput experiments. The GSE54397, GSE112369, GSE10810, GSE241585.ER, GSE24185.PR, GSE68373, and GSE38167 datasets were analyzed. A case-control study was carried out in 123 Iranian suffering from breast cancer and 132 participants as control samples as well as 130 people suffering from gastric cancer and 54 people as control group members. SNP rs6426881 in the 3′-UTR of PBX1 was genotyped by the High-Resolution Melting (HRM) method. Association analysis revealed that rs6426881 is correlated with Estrogen and Progesterone receptors, grade, and stage of breast cancer. Furthermore, a significant relationship was observed between the genotypes and blood groups in gastric cancer, while the distribution of alleles was significantly related to smoking, status of the primary tumor, and metastasis (Chi-Square P < 0.05). Finally, Bioinformatics analyses suggested that rs6426881 contains binding sites for miR-522-3p in the 3′-UTR of PBX1 transcript. The finding suggested that TT genotype is associated with poor prognosis in breast and gastric cancer. Conclusions The rs6426881 T allele at PBX1 3′-UT is significantly related to breast and gastric cancers by altering the regulatory affinity of miR-522-3p to PBX1 3′-UTR and may be suggested as a novel prognostic biomarker for the diseases.

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