Expression of miRNA-26b-5p and its Target TRPS1 Show Association with Post-Chernobyl Breast Cancer Development

Abstract

Ionizing radiation is a wellâ€recognized risk factor for the development of breast cancer. However, it is unknown whether radiationâ€specific molecular oncogenic mechanisms exist. Female clean-up workers diagnosed with breast cancer who worked at the Chernobyl site, post meltdown, were investigated for any molecular changes when compared to nonexposed controls. Increased expression of miRNAâ€26bâ€5p was found to be associated with radiation exposure in the subjects that were observed. Moreover, downregulation of the TRPS1 protein, which is a transcriptional target of miRNAâ€26bâ€5p, was linked to radiation exposure. Given that TRPS1 overexpression is common in sporadic breast cancer, its observed downregulation in radiationâ€associated breast cancer warrants clarification of the specific functional role of TRPS1 in the radiation context. Subsequently, the impact of TRPS1 was characterized in two radiationâ€transformed breast cell culture models. The subsequent deregulated genes were associated with DNAâ€repair, cell cycle, mitosis, cell migration, angiogenesis and EMT pathways. The genes correlating with TRPS1 in the radiationâ€transformed breast cell lines were primarily linked to DNA damage response and chromosome segregation, while the transcriptional interaction partners in the sporadic breast cancers were mostly associated with apoptosis. The continued study of how miRNA-26b-5p upregulation and the interrelated TRPS1 downregulation relates to the increase in radiation induced breast cancer formation may lead to the creation of beneficial therapeutic treatments that may halt and prevent this specific type of cancer.