Dysregulations of long non-coding RNAs - The emerging "lnc" in environmental carcinogenesis

Abstract

Long non-coding RNAs (lncRNAs) refer to a class of RNA molecules that are more than 200 nucleotides in length and usually lack protein-coding capacity. LncRNAs play important roles in regulating gene expression as well as many aspects of normal physiological processes. Dysregulations of lncRNA expressions and functions are considered to be critically involved in the development and progression of many diseases especially cancer. The lncRNA research in the field of cancer biology over the past decade reveals that a large number of lncRNAs are dysregulated in various types of cancer and that dysregulated lncRNAs may play important roles in cancer initiation, metastasis and therapeutic responses. Metal carcinogens and other common environmental carcinogens such as polycyclic aromatic hydrocarbons, fine particular matters, cigarette smoke, ultraviolet and ionizing radiation are important cancer etiology factors. However, the mechanisms of how metal carcinogens and other common environmental carcinogen exposures initiate cancer and promote cancer progression remain largely unknown. Accumulating evidence show that exposure to metal carcinogens and other common environmental carcinogens dysregulate lncRNA expression in various model systems, which may offer novel mechanistic insights for environmental carcinogenesis. This review will first provide a brief introduction about lncRNA biology and the mechanisms of lncRNA functions, followed by summarizing and discussing recent studies about lncRNA dysregulation by metal carcinogen and other common environment carcinogen exposures and the potential roles of dysregulated lncRNAs in environmental carcinogenesis. A perspective for future studies in this emerging and important field is also presented.

Keywords: Arsenic; Cadmium; Chromium; Environmental carcinogenesis; Environmental carcinogens; Epigenetics; Long non-coding RNAs; Metal carcinogenesis; Metals; Nickel.

Figure 1.

A briefly summary on the mechanisms of lncRNA functions. (A) LncRNAs interact with DNA or chromatin. LncRNAs can bind to DNAs directly or indirectly, regulating target genes at its transcription level. They also can recruit specific histone-modifying enzymes (HMEs) or chromatin modification complexes to different chromatin regions, activating or silencing gene expressions. (B) LncRNAs interact with mRNA or miRNAs. LncRNAs can modulate mRNA maturation by interacting with specific RNA-binding protein (RBP) components in spliceosomes. They also affect target mRNA stability and translation through modulating its post-transcriptional level. Moreover, they can function as sponges or decoys to sequester miRNA biofunctions. (C) LncRNAs interact with multiple proteins. LncRNAs can serve as scaffolds for assembly of ribonucleoprotein (RNP) complexes interacting with other protein partners. In addition, they can enhance protein stability or participate in the regulation of protein turnover. Furthermore, they can facilitate nuclear protein transport to various subcellar location, or vice versa.

Figure 2.

A schematic description on the proposed effects and mechanisms of environmental carcinogen exposure-caused lncRNA dysregulations and their roles in environmental carcinogenesis.