Arsenic-induced changes in miRNA expression in cancer and other diseases

Abstract

miRNAs (miRNA) are essential players regulating gene expression affecting cellular processes contributing to disease development. Dysregulated miRNA expression has been observed in numerous diseases including hepatitis, cardiovascular diseases and cancers. In cardiovascular diseases, several miRNAs function as mediators of pathogenic stress-related signaling pathways that may lead to an excessive extracellular matrix production and collagen deposition causing cardiac stress resulting in fibrosis. In cancers, many miRNAs function as oncogenes or tumor suppressors facilitating tumor growth, invasion and angiogenesis. Furthermore, the association between distinct miRNA profile and tumor development, progression and treatment response has identified miRNAs as potential biomarkers for disease diagnosis and prognosis. Growing evidence demonstrates changes in miRNA expression levels in experimental settings or observational studies associated with environmental chemical exposures such as arsenic. Arsenic is one of the most well-known human carcinogens. Long-term exposure through drinking water increases risk of developing skin, lung and urinary bladder cancers, as well as cardiovascular disease. The mechanism(s) by which arsenic causes disease remains elusive. Proposed mechanisms include miRNA dysregulation. Epidemiological studies identified differential miRNA expression between arsenic-exposed and non-exposed individuals from India, Bangladesh, China and Mexico. In vivo and in vitro studies have shown that miRNAs are critically involved in arsenic-induced malignant transformation. Few studies analyzed miRNAs in other diseases associated with arsenic exposure. Importantly, there is no consensus on a consistent miRNA profile for arsenic-induced cancers because most studies analyze only particular miRNAs. Identifying miRNA expression changes common among humans, rodents and cell lines might guide future miRNA investigations.

Keywords: Arsenic; Carcinogenesis; miRNA dysregulation.

FIGURE 1

Diagram of literature search and selection process of the studies. *Others category included studies on bioinformatics analysis, plants, and non-English written. The sum of all 5 categories (epidemiological, in vivo, in vitro, review and others) in the initial set is > 200 because some studies assessed more than one category.

FIGURE 2

The fate of the targeting mRNA depends on the complementarity of the seed sequence (nucleotides 2 to 8 on the 5’ end of the miRNA) to the mRNA. A continuous base-pairing promotes mRNA deadenylation or degradation. Imperfect base-pairing inhibits translation [21]. Adapted from [98].