Long non-coding RNAs as novel expression signatures modulate DNA damage and repair in cadmium toxicology

Abstract

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in a variety of physiological and pathophysiological processes. Our study was to investigate whether lncRNAs as novel expression signatures are able to modulate DNA damage and repair in cadmium(Cd) toxicity. There were aberrant expression profiles of lncRNAs in 35th Cd-induced cells as compared to untreated 16HBE cells. siRNA-mediated knockdown of ENST00000414355 inhibited the growth of DNA-damaged cells and decreased the expressions of DNA-damage related genes (ATM, ATR and ATRIP), while increased the expressions of DNA-repair related genes (DDB1, DDB2, OGG1, ERCC1, MSH2, RAD50, XRCC1 and BARD1). Cadmium increased ENST00000414355 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood ENST00000414355 expression and urinary/blood Cd concentrations, and there were significant correlations of lncRNA-ENST00000414355 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. These results indicate that some lncRNAs are aberrantly expressed in Cd-treated 16HBE cells. lncRNA-ENST00000414355 may serve as a signature for DNA damage and repair related to the epigenetic mechanisms underlying the cadmium toxicity and become a novel biomarker of cadmium toxicity.

Melatonin antagonizes cadmium‐induced neurotoxicity by activating the transcription factor EB‐dependent autophagy–lysosome machinery in mouse neuroblastoma cells

“…We propose that "TFEB-responsive genes" might also be regulated by epigenetic modifications, such as noncoding RNAs, in Cd-induced neurotoxicity. 46,47 Further investigation is required to determine how LAMP1 protein level is reduced in this model system.…”

“…Interestingly, although Cd elevated Lamp1 mRNA levels, LAMP1 protein levels were significantly decreased after Cd exposure. We propose that “TFEB‐responsive genes” might also be regulated by epigenetic modifications, such as noncoding RNAs, in Cd‐induced neurotoxicity . Further investigation is required to determine how LAMP1 protein level is reduced in this model system.…”

Long non-coding RNA PICART1 suppresses proliferation and promotes apoptosis in lung cancer cells by inhibiting JAK2/STAT3 signaling

“…LncRNAs are known to be involved in multiple key cellular processes; including genomic imprinting, RNA processing, chromatin modification and the modulation of apoptosis and invasion [18][19][20][21]. Emerging evidence shows that lncRNAs are essential for the development of malignant lung tumor carcinogenesis, and these have emerged as biomarkers for tumor prediction and diagnosis [7,22,23].…”

Next generation deep sequencing identified a novel lncRNA n375709 associated with paclitaxel resistance in nasopharyngeal carcinoma

“…Aberrant expression and dysfunction of lncRNAs in cancers, along with its tissue specific expression pattern, indicates specific-lncRNAs may be used as promising targets for the development of novel anticancer therapy ( 30 – 32 ). So far, multiple strategies have been proposed to restore the homeostatic levels of lncRNAs, in which siRNA is one of the most frequently used approaches to inhibit the upregulation of oncogenic lncRNAs ( 35 , 36 ). These siRNAs are complementary to target lncRNAs and induce degradation in RISC (RNA-induced silencing) complex, and consequently decline the levels of lncRNA transcripts ( 37 ).…”