Serum hsa-circ-0025244 as a biomarker in Chinese occupational mercury-exposed population and mediate apoptosis through JNK/p38 MAPK signaling pathway.

BACKGROUND:circRNAs have been recognized as biomarkers of numerous diseases. We would like to explore the expression pattern and molecular mechanisms of circRNAs in the Chinese occupational mercury-exposed population. METHODS:The workers from a thermometer manufacturing plant and lamp factory in Jiangsu province of China were recruited in 2016. Blood samples were collected from the subjects with chronic mercury poisoning group, mercury absorption group, and the healthy controls. The differentially expressed circRNAs (DECRs) between the three groups were screened from serum samples using a circRNA microarray. The significant DECRs were validated by qRT-PCR, and their respective diagnostic values for mercury poisoning and mercury absorption were analyzed by receiver operating characteristic (ROC) curves. For in vitro experiments, 293T cells were treated with different doses of HgCl2 to determine the half-lethal concentration. The cells were transfected with the siRNA construct or expression plasmid of circRNA. The expression levels of JNK, p38, and caspase family proteins were analyzed by Western blotting. RESULTS:hsa_circ_0025244 was up-regulated in the mercury poisoning and absorption groups compared to the control group (P < 0.05), and positively correlated with the urine mercury levels (P < 0.05). The area under the ROC curve (AUC) of hsa_circ_0025244 for diagnosing occupational mercury poisoning was 0.748, indicating moderate accuracy (P < 0.001). Moreover, the diagnostic accuracy of occupational mercury absorption was high (P < 0.001) with an AUC of 0.918. Knockdown of hsa_circ_0025244 in 293T cells significantly reduced the expression levels of JNK/p38, and caspase family proteins compared to that in the control cells (P < 0.01), and its overexpression led to opposite effects (P < 0.05). CONCLUSIONS:hsa_circ_0025244 is a potential biomarker for mercury exposure and mediates mercury-induced apoptosis in 293T cells by activating the JNK/p38 MAPK signaling pathway.