Long non-coding RNA ENST00000414355 as a biomarker of cadmium exposure regulates DNA damage and apoptosis

Abstract

Human exposure to cadmium (Cd) may induce severe effects in different organs. Recent studies suggest that long non-coding RNAs (lncRNAs) are closely involved in the pathophysiological mechanisms of Cd-related diseases. This study evaluated the use of lncRNA (ENST00000414355) as an expression signature of Cd exposure and assessed its ability to modulate DNA damage and apoptosis by measuring the expression of ATM serine/threonine kinase (ATM) and mitochondrial membrane potential (ΔΨm) in Cd-exposed workers. A total of 139 (74 non-smokers and 65 smokers) participants from a Cd battery manufacturer were included in the study. Venous blood samples were collected to determine the blood Cd level and detect blood ENST00000414355 and its target gene (ATM) using real-time reverse transcription-polymerase chain reaction (qRT-PCR). Mitochondrial membrane potential was used to assess the Cd effect on mitochondrial permeability. Our results indicated a significant positive correlation between blood Cd level and lncRNA-ENST00000414355 and ATM expression and a significant negative correlation between blood Cd level and ΔΨm ( p < 0.0001). Moreover, significant correlations were observed between the expression of lncRNA-ENST00000414355 and ATM expression and ΔΨm ( p < 0.0001). Statistical significance was found in the blood Cd level, lncRNA-ENST00000414355 expression, ATM expression, and ΔΨm ( p < 0.0001) between smokers and non-smokers. This study confirmed the upregulation of the lncRNA-ENST00000414355 expression, DNA damage-checkpoint-related gene (ATM), and decreased ΔΨm in Cd-exposed workers. Thus, lncRNA-ENST00000414355 may serve as a valuable biomarker for the exposure and toxicity of Cd.

Oxidative Stress and Its Role in Cd-Induced Epigenetic Modifications: Use of Antioxidants as a Possible Preventive Strategy

“…Other ncRNAs that have been affected by Cd exposure are LncRNAs. A study conducted on workers exposed to Cd found a significant positive correlation between the level of Cd in the blood and LncRNA-ENST00000414355 and serine/threonine kinase (ATM) expression and a significant negative correlation between the level of Cd in the blood and the ∆Ψm [190]. Another study reported that a maternally expressed tumor suppressor LncRNA 3 (MEG3) is significantly downregulated in BEAS-2B cells transformed with Cd [191].…”