Wang Zhishan, Wang Po-Shun, Yang Chengfeng
Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, 11794, USA.
Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, 101 Nicolls Road, Stony Brook, NY, 11794, USA.
Curr Environ Health Rep. 2024 Dec 23;12(1):3. doi: 10.1007/s40572-024-00468-1.
Metals are common environmental pollutants. Acute and chronic exposures to non-essential toxic metals or excessive essential metals cause various diseases including cancer in humans. However, the underlying mechanisms have not been well understood. Long non-coding RNAs (lncRNAs) refer to RNA transcripts that have more than 200 nucleotides but do not have significant protein coding capacities. While lncRNAs were once considered transcription noise, they have become increasingly recognized as crucial players in various physiological and pathogenesis processes. The goal of this article is to review and discuss recent studies that show important roles of lncRNA dysregulations in metal toxicity and carcinogenesis.
Recent studies showed that metal exposures dysregulate expression of lncRNAs in cultured cells, animals and humas. However, only a few studies determined the mechanisms of how metal exposure dysregulated expression of lncRNAs. The majority of the studies reported the association of abnormally expressed lncRNAs with various toxic effects of metal exposures, only limited studies established causal relationships demonstrating causal roles of dysregulated lncRNAs in metal toxicity and carcinogenesis. Mechanistically, most studies reported that dysregulated lncRNAs functioned as microRNA sponges to regulate gene expression, much less studies explored other mechanisms of lncRNA actions. It is evident that metal exposures dysregulate expression of lncRNAs, which may serve as novel mediators in metal toxicity and carcinogenesis. Further studies are needed to establish dysregulated lncRNAs as potential diagnostic biomarkers and therapeutic targets for metal exposure-associated diseases.
金属是常见的环境污染物。急性和慢性接触非必需的有毒金属或过量的必需金属会导致包括人类癌症在内的各种疾病。然而，其潜在机制尚未得到充分理解。长链非编码RNA（lncRNA）是指长度超过200个核苷酸但没有显著蛋白质编码能力的RNA转录本。虽然lncRNA曾被认为是转录噪音，但它们越来越被认为是各种生理和发病过程中的关键参与者。本文的目的是综述和讨论最近的研究，这些研究表明lncRNA失调在金属毒性和致癌作用中发挥重要作用。
最近的研究表明，金属暴露会使培养细胞、动物和人类中的lncRNA表达失调。然而，只有少数研究确定了金属暴露导致lncRNA表达失调的机制。大多数研究报告了异常表达的lncRNA与金属暴露的各种毒性作用之间的关联，只有有限的研究建立了因果关系，证明失调的lncRNA在金属毒性和致癌作用中的因果作用。从机制上讲，大多数研究报告说，失调的lncRNA作为微小RNA海绵发挥作用来调节基因表达，探索lncRNA作用其他机制的研究要少得多。显然，金属暴露会使lncRNA表达失调，lncRNA可能是金属毒性和致癌作用中的新型介质。需要进一步研究将失调的lncRNA确立为金属暴露相关疾病的潜在诊断生物标志物和治疗靶点。
