MicroRNA Responses to Cellular Stress

TLDR

MicroRNAs are key regulators of development and tumor biology, with distinct expression patterns defining developmental programs and altered profiles observed in neoplasia. The study aimed to determine whether stressors linked to developmental defects and cancer, such as folate deficiency, radiation, and arsenic, modify miRNA expression. Human lymphoblastoid cells were profiled for 385 miRNAs using microarrays under different stress conditions. Folate deficiency and arsenite exposure caused global upregulation of miRNAs, including significant overexpression of hsa‑miR‑222, whereas γ‑irradiation had no effect, indicating that altered miRNA profiles may serve as biomarkers of these toxic exposures. Cancer Res 2006; 66(22): 10843‑8.

Abstract

Abstract Recent work has begun to explore the instrumental role that small noncoding RNA species, particularly microRNAs (miRNA), have both in classifying human tumors and in directing embryonic development. These studies suggest that developmental programs in essentially all organisms studied are set, in part, by varied expressions of miRNAs and that neoplasia is characterized by altered expression of miRNAs. Reasoning that these observations are linked, we examined whether cellular exposures that induce both developmental anomalies and cancer alter miRNAs. Using microarrays of 385 known human miRNAs, we studied human lymphoblastoid cells grown under various conditions or treatments. Folate deficiency induced a pronounced global increase in miRNA expression. We observed no significant alteration in miRNA expression in cells treated with γ-irradiation, whereas exposure to sodium arsenite led to global increases in miRNA expression. The miRNA hsa-miR-222 was identified from these arrays as significantly overexpressed under folate-deficient conditions, and this finding was confirmed in vivo in human peripheral blood from individuals with low folate intake. Alterations to cellular miRNA expression profiles represent a novel mode of action of folate deprivation and arsenic exposure, and specific alterations in miRNA expression may be a powerful biomarker for these and other toxins with serious effects on human health. (Cancer Res 2006; 66(22): 10843-8)