Expression of miRNA‐26b‐5p and its target TRPS1 is associated with radiation exposure in post‐Chernobyl breast cancer

Abstract

Ionizing radiation is a well-recognized risk factor for the development of breast cancer. However, it is unknown whether radiation-specific molecular oncogenic mechanisms exist. We investigated post-Chernobyl breast cancers from radiation-exposed female clean-up workers and nonexposed controls for molecular changes. Radiation-associated alterations identified in the discovery cohort (n = 38) were subsequently validated in a second cohort (n = 39). Increased expression of hsa-miR-26b-5p was associated with radiation exposure in both of the cohorts. Moreover, downregulation of the TRPS1 protein, which is a transcriptional target of hsa-miR-26b-5p, was associated with radiation exposure. As TRPS1 overexpression is common in sporadic breast cancer, its observed downregulation in radiation-associated breast cancer warrants clarification of the specific functional role of TRPS1 in the radiation context. For this purpose, the impact of TRPS1 on the transcriptome was characterized in two radiation-transformed breast cell culture models after siRNA-knockdown. Deregulated genes upon TRPS1 knockdown were associated with DNA-repair, cell cycle, mitosis, cell migration, angiogenesis and EMT pathways. Furthermore, we identified the interaction partners of TRPS1 from the transcriptomic correlation networks derived from gene expression data on radiation-transformed breast cell culture models and sporadic breast cancer tissues provided by the TCGA database. The genes correlating with TRPS1 in the radiation-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. Thus, upregulation of hsa-miR-26b-5p and downregulation of TRPS1 in radiation-associated breast cancer tissue samples suggests these molecules representing radiation markers in breast cancer.

Chemical compound cinobufotalin potently induces FOXO1-stimulated cisplatin sensitivity by antagonizing its binding partner MYH9

“…MiRNA-induced suppression of gene expression mainly occurs at the posttranscriptional level. 35–37 We searched databases (microRNA.org and TargetScan) and found that miR-133a-3p, a tumor suppressor in some tumors, 38,39 could directly target MYH9. Furthermore, we confirmed that miR-133a-3p, a tumor suppressor, directly downregulated MYH9 protein expression by binding to its 3’UTR in NPC cells.…”

Transcriptional activation of miR-320a by ATF2, ELK1 and YY1 induces cancer cell apoptosis under ionizing radiation conditions

“…The role of miRNAs, which are associated with multiple facets of cellular activities, is one of the most important and exciting emerging paradigms in cell biology. Accumulating genetic evidence indicates that miRNAs also play an essential part in stress responses, such as hypoxia, hydrogen peroxide (H 2 O 2 ) and ionizing radiation (IR) (2)(3)(4)(5). For example, it has been reported that several miRNAs are regulated by IR treatment (6,7).…”

miRNAs as radio‐response biomarkers for breast cancer stem cells

“…Equally, the overexpression of miR‐182 confers radioresistance in non‐small‐cell lung cancer (Chen et al , ). In addition, mir‐26b increased in radiation‐associated BC in female post‐Chernobyl clean‐up workers in comparison with nonexposed control (Wilke et al , ). These miRNAs related to radiation exposure associated with DNA damage response and tumor progression could represent radiation markers in BC.…”

“…Hence, miRNA expression changes could be useful for monitoring exposures and understanding regulation in response to radiation‐induced DNA damage (Cellini et al , ; Czochor and Glazer, ); for example, studies have shown that miR‐125b and miR‐139 could be useful biomarkers of radiosensitivity (Metheetrairut et al , ; Pajic et al , ). Alike, it has been observed that the overexpression of miR‐26‐5p after radiation exposure is related to processes of breast carcinogenesis or that the miR‐223 expression (a potential tumor suppressor) in BC patients after radiation treatment restrains recurrence formation via EGF/EGFR pathway (Fabris et al , ; Wilke et al , ). For these reasons, miRNAs could be good cancer biomarkers for diagnostic, prognostic, and treatment response that could improve the efficacy of current cancer therapy (Halvorsen et al , ; Schwarzenbacher et al , ).…”