Altered microRNA expression profiles are involved in resistance to low-dose ionizing radiation in the absence of BMI1 in human dermal fibroblasts

Abstract

The polycomb group RING finger protein, B-cell-specific moloney murine leukemia virus integration site 1 (BMI1), has emerged as a key regulator of cell proliferation, cell cycle, cell immortalization, chemoresistance and radioresistance. Although the radioresistant effect of BMI1 has been thoroughly investigated, the effectiveness of this factor on low-dose radiation (LDR) resistance has not been explored. Here, we demonstrate that BMI1 is not critical for altering cell viability or cell growth in response to LDR, but BMI1 changes cellular gene expression profiles in response to LDR. Normal human dermal fibroblasts (NHDFs) stably expressing BMI1 short hairpin RNA (shRNA) did not exhibit changes in cell viability or cell cycle distribution assays following exposure to 0.1 Gy of γ-radiation. However, microRNA (miRNA) microarrays revealed that a lack of BMI1 leads to changes in miRNA expression in response to LDR. Bioinformatics analyses demonstrated that predicted target genes of the altered miRNAs are functionally involved in both negative and positive regulation of cell growth, cell proliferation, cell cycle and apoptosis. Therefore, these results indicate that low radiosensitivity even in the absence of the radioresistant factor BMI1 is related with the altered miRNA expression profiles in NHDF.