Coal combustion related fine particulate matter (PM_2.5) induces toxicity in Caenorhabditis elegans by dysregulating microRNA expression.

ABSTRACT: We employed an in vivo assay system of Caenorhabditis elegans to determine if and which microRNAs (miRNAs) were dysregulated upon exposure to coal combustion related fine particulate matter (PM_2.5) by profiling the miRNAs using SOLiD sequencing. From this, expression of 25 miRNAs was discovered to become dysregulated by exposure to PM_2.5. Using the corresponding C. elegans deletion mutants, 5 miRNAs (mir-231, mir-232, mir-230, mir-251 and mir-35) were found to be involved in the control of PM_2.5 toxicity. Furthermore, mutation of mir-231 or mir-232 induced a resistance to PM_2.5 toxicity, whereas mutation of mir-230, mir-251, or mir-35 induced a susceptibility to PM_2.5 toxicity. SMK-1, an ortholog of the mammalian SMEK protein, was identified as a molecular target for mir-231 in the regulation of PM_2.5 toxicity. In addition, the genes of sod-3, sod-4 and ctl-3, which are necessary for protection against oxidative stress, were determined to be important downstream targets of smk-1 in the regulation of PM_2.5 toxicity. The triggering of this mir-231-SMK-1-SOD-3/SOD-4/CTL-3 signaling pathway may be a critical molecular basis for the role of oxidative stress in the induction of coal combustion related PM_2.5 toxicity.

SUBMITTER: Wu Q 

PROVIDER: S-EPMC6062267 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature