miR-155 rs767649 T>A gene polymorphism is associated with downregulation of miR-155 expression, suppressor of cytokine signaling-1 overexpression, and low probability of metastatic tumor at the time of breast cancer diagnosis.

Abstract

Background: MicroRNA-155 is a key player in inflammatory reactions, carcinogenesis, and tumor development. In this study, polymorphism of miRNA-155 rs767649 T>A and its gene and suppressor of cytokine signaling-1 (SOCS-1) expression were investigated in relation to cancer susceptibility and development in breast cancer (BC) patients.

Materials and methods: Polymorphism of miRNA-155 rs767649 T>A was evaluated between a population of 174 patients with BC and 129 controls using restriction fragment length polymorphism and the expression of miR-155 and SOCS-1 were examined in peripheral blood mononuclear cells (PBMCs) by real-time polymerase chain reaction.

Results: TT genotype of miR-155 rs767649 T>A was associated with higher level of miR-155 in PBMCs of BC patients relative to AT and AA genotypes (21.76 ± 4.4, 4.046 ± 1.35, 2.56 ± 0.81, respectively; P < 0.001) and increased lymph node metastasis (r = 0.292, P = 0.001), not BC susceptibility (P = 0.402 and P = 0.535; respectively). TT genotype of miR-155 rs767649 T>A was associated with less gene expression of SOCS-1 in PBMCs of BC patients compared to AT and AA genotypes (1.173 ± 0.57, 0.92 ± 0.827, 5.512 ± 0.92, respectively; P = 0.003).

Conclusion: This study demonstrated for the first time the association between the T allele of the rs767649 T>A polymorphism in the pre-MIR155 gene and higher expression of miR-155, lower expression of SOCS-1, and swift latent progression in newly diagnosed BC patients. Thus, miR-155 may play a critical role in BC pathogenesis.