Long noncoding RNAs: emerging players in thyroid cancer pathogenesis

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   Figure 1

   lncRNAs and their functions. This illustration shows various functions of lncRNAs. In the nucleus, lncRNAs are involved in chromatin looping, chromatin modification in both cis and trans, transcription regulation (activation or repression) and mRNA splicing. lncRNAs target mRNA for degradation or protection, transcription factor trafficking, miRNA site masking and translation disruption/ribosome targeting in the cytoplasm. A full colour version of this figure is available at https://doi.org/10.1530/ERC-17-0188.
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   Figure 2

   Tumor-suppressive effects of various lncRNAs in thyroid cancer. Thyroid cancer-specific lncRNAs shown above regulate expression by repressing/tightly controlling transcription of various genes involved in proliferation, cell cycle regulation, cell motility, etc. In thyroid cancer, context-dependent downregulation of these lncRNAs results in transcriptional activation of various genes of key cellular signaling pathways. A full colour version of this figure is available at https://doi.org/10.1530/ERC-17-0188.
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   Figure 3

   Various oncogenic lncRNAs implicated in thyroid cancer. Deregulation of various lncRNAs is implicated in thyroid cancer. lncRNAs regulate expression by controlling transcription of various genes involved in the key cellular processes such as proliferation, cell cycle, survival, apoptosis, cell motility, etc. In thyroid cancer, context-dependent upregulation of these lncRNAs results in transcriptional activation of various genes of important cell signaling pathways that result in deregulated cellular processes paving the way to carcinogenesis. A full colour version of this figure is available at https://doi.org/10.1530/ERC-17-0188.
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   Figure 4

   Oncogenic effect of PVT1 and BANCR lncRNAs in thyroid cancer. lncRNAs PVT1 and BANCR activate the transcription of various genes implicated in regular cell growth signaling pathways of normal thyroid cells. Deregulation of lncRNA machinery results and upregulation of lncRNAs PVT1 and BANCR that hyperactivate the transcription of various key cellular growth controlling genes in thyroid cancer. A full colour version of this figure is available at https://doi.org/10.1530/ERC-17-0188.
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   Figure 5

   Schematic representation of various lncRNA-targeting agents and their mechanisms. Deregulated lncRNAs in cancer cells are targeted using various molecules such as siRNA, an antisense oligonucleotide, ribozyme, aptamer, small molecules, etc. siRNAs: guide strands initially loaded to AGO2 (argonaute 2) that results in formation of RISC (an active RNA-induced silencing complex). RISC binds to the target RNA by complementary base pairing and cleaves the target RNA. ASOs: RNAse-H identifies the DNA–RNA duplex and cleaves the RNA target. Ribozyme: catalyzes the cleavage of the flanked RNA region downstream to a NUH site via destabilizing the phosphodiester backbone of target RNA. Aptamers: bind to their target lncRNAs specifically fitting to the 3-D structures of lncRNA and suppress the interactions of lncRNAs. Small molecules: specifically bind to the RNA binding pockets of lncRNAs, and compete with protein factors/intracellular small ligands for the binding of lncRNAs. It causes conformational distortion within lncRNA which results in suppression of unique lncRNA. These target-specific molecular agents have an efficient binding capacity and destroy the targeted lncRNAs that exclusively depend on the cellular context. A full colour version of this figure is available at https://doi.org/10.1530/ERC-17-0188.

• © 2018 Society for Endocrinology