Arsenic exposure increased expression of HOTAIR and LincRNA-p21 in vivo and vitro

Arsenic is an environmental contaminant, its multiple effects on human tend to increase the rate of disease, cancer and other health problems. Some of long non-coding RNAs (lncRNAs) can be induced in major cellular processes such as necrosis, proliferation, and mutation. While the toxicity of arsenic is well established, the association between arsenic exposure and long non-coding RNAs has not been studied enough. This study investigated the association between arsenic and the expression of HOTAIR and LincRNA-p21 in vivo and vitro. In epidemiological studies, the expression of HOTAIR and LincRNA-p21 was increased after long-term arsenic exposure. HOTAIR and LincRNA-p21 expression were positively linked to monomethylarsenic acid (MMA), dimethylarsenic acid (DMA), inorganic arsenic (iAs), total arsenic (tAs), and MMA% and negatively linked to secondary methylation index (SMI). In A549 cells, arsenic exposure resulted in enhanced HOTAIR and LincRNA-p21 expression dose-dependently. The expression of HOTAIR was considerably high in the presence of NaAsO₂ and MMA but showed no difference in DMA compared with control group. And LincRNA-p21 expression was increased in the presence of NaAsO₂, MMA, and DMA. The expression of HOTAIR and LincRNA-p21 induced by iAs was much higher than that induced by MMA and DMA. Compared with the control group, treatment of A549 cells with NaAsO₂/S-adenosylmethionine (SAM) and NaAsO₂/glutathione (GSH) combination increased HOTAIR and LincRNA-p21 expression. The expression of LincRNA-p21 in combination of NaAsO₂/GSH was significantly decreased compared with NaAsO₂ alone. Besides, in the presence of arsenic, both of HOTAIR and LincRNA-p21 were upregulated significantly when P53 was knocked down. We revealed that inorganic arsenic, its methylated metabolites, and arsenic metabolism efficiency affect the expression of HOTAIR and LincRNA-p21.