Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Long non-coding RNAs as regulators of the endocrine system

Key Points

  • A substantial proportion of the genome is transcribed into non-coding RNAs, including many long non-coding RNAs (lncRNAs) that are important regulators of endocrine cells

  • Many research findings point towards an important role of lncRNAs in regulating the development and maintenance of endocrine organs and hormonal signalling; misregulation of these processes can lead to disease

  • The biological functions of lncRNAs in endocrine organs are poorly understood; genetic models are needed to fully assess the role of lncRNAs in a variety of homeostatic processes in vivo

  • lncRNAs can be potentially developed as novel diagnostic markers to identify and classify certain tumours

Abstract

Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2: Mechanisms of lncRNA action.
Figure 3: Endocrine organs and lncRNAs.

Similar content being viewed by others

References

  1. Amaral, P. P., Dinger, M. E., Mercer, T. R. & Mattick, J. S. The eukaryotic genome as an RNA machine. Science 319, 1787–1789 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Kapranov, P. et al. Large-scale transcriptional activity in chromosomes 21 and 22. Science 296, 916–919 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Kapranov, P. et al. Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. Genome Res. 15, 987–997 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wahlestedt, C. Natural antisense and noncoding RNA transcripts as potential drug targets. Drug Discov. Today 11, 503–508 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Kawai, J. et al. Functional annotation of a full-length mouse cDNA collection. Nature 409, 685–690 (2001).

    Article  PubMed  Google Scholar 

  6. Okazaki, Y. et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420, 563–573 (2002).

    Article  PubMed  Google Scholar 

  7. Rinn, J. L. et al. The transcriptional activity of human chromosome 22. Genes Dev. 17, 529–540 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cabili, M. N. et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25, 1915–1927 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dunham, I. et al. The DNA sequence of human chromosome 22. Nature 402, 489–495 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Schuler, G. D. et al. A gene map of the human genome. Science 274, 540–546 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. ENCODE Project Consortium et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816 (2007).

  13. Derrien, T. et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 22, 1775–1789 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Harrow, J. et al. GENCODE: the reference human genome annotation for the ENCODE Project. Genome Res. 22, 1760–1774 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).

  16. Hangauer, M. J., Vaughn, I. W. & McManus, M. T. Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet. 9, e1003569 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jacquier, A. The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat. Rev. Genet. 10, 833–844 (2009).

    Article  CAS  PubMed  Google Scholar 

  18. Djebali, S. et al. Landscape of transcription in human cells. Nature 489, 101–108 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bertone, P. et al. Global identification of human transcribed sequences with genome tiling arrays. Science 306, 2242–2246 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Guttman, M. et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458, 223–227 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S. & Brockdorff, N. Requirement for Xist in X chromosome inactivation. Nature 379, 131–137 (1996).

    Article  CAS  PubMed  Google Scholar 

  22. Yu, W. et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451, 202–206 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gupta, R. A. et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464, 1071–1076 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kretz, M. et al. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493, 231–235 (2013).

    Article  CAS  PubMed  Google Scholar 

  25. Brannan, C. I., Dees, E. C., Ingram, R. S. & Tilghman, S. M. The product of the H19 gene may function as an RNA. Mol. Cell. Biol. 10, 28–36 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ingolia, N. T., Lareau, L. F. & Weissman, J. S. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147, 789–802 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Guttman, M. et al. Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell 154, 240–251 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chew, G.-L. et al. Ribosome profiling reveals resemblance between long non-coding RNAs and 5′ leaders of coding RNAs. Development 140, 2828–2834 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bazzini, A. A. et al. Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J. 33, 981–993 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ingolia, N. T. et al. Ribosome profiling reveals pervasive translation outside of annotated protein-coding genes. Cell Rep. 8, 1365–1379 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lam, M. T., Li, W., Rosenfeld, M. G. & Glass, C. K. Enhancer RNAs and regulated transcriptional programs. Trends Biochem. Sci. 39, 170–182 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. van Heesch, S. et al. Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes. Genome Biol. 15, R6 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Alvarez-Dominguez, J. R. et al. Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation. Blood 123, 570–581 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Necsulea, A. et al. The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505, 635–640 (2014).

    Article  CAS  PubMed  Google Scholar 

  35. Diederichs, S. The four dimensions of noncoding RNA conservation. Trends Genet. 30, 121–123 (2014).

    Article  CAS  PubMed  Google Scholar 

  36. Kutter, C. et al. Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLoS Genet. 8, e1002841 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ulitsky, I., Shkumatava, A., Jan, C. H., Sive, H. & Bartel, D. P. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147, 1537–1550 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Torarinsson, E., Sawera, M., Havgaard, J. H., Fredholm, M. & Gorodkin, J. Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. Genome Res. 16, 885–889 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Torarinsson, E. et al. Comparative genomics beyond sequence-based alignments: RNA structures in the ENCODE regions. Genome Res. 18, 242–251 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Johnsson, P. & Morris, K. V. Expanding the functional role of long noncoding RNAs. Cell Res. 24, 1284–1285 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rinn, J. L. & Chang, H. Y. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81, 145–166 (2012).

    Article  CAS  PubMed  Google Scholar 

  43. Tsai, M.-C. et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science 329, 689–693 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tripathi, V. et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol. Cell 39, 925–938 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311–1323 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang, K. C. et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472, 120–124 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hacisuleyman, E. et al. Topological organization of multichromosomal regions by the long intergenic noncoding RNA FIRRE. Nat. Struct. Mol. Biol. 21, 198–206 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Karreth, F. A. et al. In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147, 382–395 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yoon, J.-H. et al. LincRNA-p21 suppresses target mRNA translation. Mol. Cell 47, 648–655 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gong, C. & Maquat, L. E. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470, 284–288 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hansen, T. B. et al. Natural RNA circles function as efficient microRNA sponges. Nature 495, 384–388 (2013).

    Article  CAS  PubMed  Google Scholar 

  52. Haines, J. L. et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 308, 419–421 (2005).

    Article  CAS  PubMed  Google Scholar 

  53. Hindorff, L. A. et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl Acad. Sci. USA 106, 9362–9367 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  54. St Laurent, G., Vyatkin, Y. & Kapranov, P. Dark matter RNA illuminates the puzzle of genome-wide association studies. BMC Med. 12, 97 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kapranov, P. et al. The majority of total nuclear-encoded non-ribosomal RNA in a human cell is 'dark matter' un-annotated RNA. BMC Biol. 8, 149 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kumar, V. et al. Human disease-associated genetic variation impacts large intergenic non-coding RNA expression. PLoS Genet. 9, e1003201 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chen, G. et al. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res. 41, D983–D986 (2013).

    Article  CAS  PubMed  Google Scholar 

  58. Hrdlickova, B., de Almeida, R. C., Borek, Z. & Withoff, S. Genetic variation in the non-coding genome: Involvement of micro-RNAs and long non-coding RNAs in disease. Biochim. Biophys. Acta 1842, 1910–1922 (2014).

    Article  CAS  PubMed  Google Scholar 

  59. Ning, S. et al. LincSNP: a database of linking disease-associated SNPs to human large intergenic non-coding RNAs. BMC Bioinformatics 15, 152 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Morán, I. et al. Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metab. 16, 435–448 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Senée, V. et al. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat. Genet. 38, 682–687 (2006).

    Article  CAS  PubMed  Google Scholar 

  62. Cho, Y. S. et al. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in East Asians. Nat. Genet. 44, 67–72 (2012).

    Article  CAS  Google Scholar 

  63. Nogueira, T. C. et al. GLIS3, a susceptibility gene for type 1 and type 2 diabetes, modulates pancreatic β cell apoptosis via regulation of a splice variant of the BH3-only protein Bim. PLoS Genet. 9, e1003532 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fadista, J. et al. Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism. Proc. Natl Acad. Sci. USA 111, 13924–13929 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ding, G.-L. et al. Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes 61, 1133–1142 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331–1336 (2007).

  67. Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336–1341 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Scott, L. J. et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341–1345 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Pasmant, E., Sabbagh, A., Vidaud, M. & Bièche, I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 25, 444–448 (2011).

    Article  CAS  PubMed  Google Scholar 

  70. Yap, K. L. et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol. Cell 38, 662–674 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Krishnamurthy, J. et al. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443, 453–457 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Scheele, C. et al. Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration? FASEB J. 21, 3653–3665 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Voight, B. F. et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet. 42, 579–589 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wallace, C. et al. The imprinted DLK1–MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. Nat. Genet. 42, 68–71 (2010).

    Article  CAS  PubMed  Google Scholar 

  75. Cheunsuchon, P. et al. Silencing of the imprinted DLK1–MEG3 locus in human clinically nonfunctioning pituitary adenomas. Am. J. Pathol. 179, 2120–2130 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Rosen, E. D. & Spiegelman, B. M. Adipocytes as regulators of energy balance and glucose homeostasis. 444, 847–853 (2006).

  77. Chooniedass-Kothari, S. et al. The steroid receptor RNA activator is the first functional RNA encoding a protein. FEBS Lett. 566, 43–47 (2004).

    Article  CAS  PubMed  Google Scholar 

  78. Sun, L. et al. Long noncoding RNAs regulate adipogenesis. Proc. Natl Acad. Sci. USA 110, 3387–3392 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Nukitrangsan, N. et al. Effect of Peucedanum japonicum Thunb on the expression of obesity-related genes in mice on a high-fat diet. J. Oleo Sci. 60, 527–536 (2011).

    Article  CAS  PubMed  Google Scholar 

  80. Seo, J. et al. Atf4 regulates obesity, glucose homeostasis, and energy expenditure. Diabetes 58, 2565–2573 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Rubi, B., del Arco, A., Bartley, C., Satrustegui, J. & Maechler, P. The malate–aspartate NADH shuttle member Aralar1 determines glucose metabolic fate, mitochondrial activity, and insulin secretion in β cells. J. Biol. Chem. 279, 55659–55666 (2004).

    Article  CAS  PubMed  Google Scholar 

  82. Lee, E. K. et al. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor γ expression. Mol. Cell. Biol. 31, 626–638 (2011).

    Article  CAS  PubMed  Google Scholar 

  83. Zhao, X. Y., Li, S., Wang, G. X., Yu, Q. & Lin, J. D. A long noncoding RNA transcriptional regulatory circuit drives thermogenic adipocyte differentiation. Mol. Cell 55, 372–382 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kopecky, J., Clarke, G., Enerbäck, S., Spiegelman, B. & Kozak, L. P. Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J. Clin. Invest. 96, 2914–2923 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Xu, B. et al. Dax-1 and steroid receptor RNA activator (SRA) function as transcriptional coactivators for steroidogenic factor 1 in steroidogenesis. Mol. Cell. Biol. 29, 1719–1734 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ginger, M. R., Gonzalez-Rimbau, M. F., Gay, J. P. & Rosen, J. M. Persistent changes in gene expression induced by estrogen and progesterone in the rat mammary gland. Mol. Endocrinol. 15, 1993–2009 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Ginger, M. R. et al. A noncoding RNA is a potential marker of cell fate during mammary gland development. Proc. Natl Acad. Sci. USA 103, 5781–5786 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Shore, A. N. et al. Pregnancy-induced noncoding RNA (PINC) associates with polycomb repressive complex 2 and regulates mammary epithelial differentiation. PLoS Genet. 8, e1002840 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Askarian-Amiri, M. E. et al. SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA 17, 878–891 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Coon, S. L. et al. Circadian changes in long noncoding RNAs in the pineal gland. Proc. Natl Acad. Sci. USA 109, 13319–13324 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Hah, N. et al. A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells. Cell 145, 622–634 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Li, W. et al. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498, 516–520 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bhan, A. et al. Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol. J. Mol. Biol. 425, 3707–3722 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Shi, Y. et al. Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes Dev. 15, 1140–1151 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Hatchell, E. C. et al. SLIRP, a small SRA binding protein, is a nuclear receptor corepressor. Mol. Cell 22, 657–668 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Silva, J. M. et al. Identification of long stress-induced non-coding transcripts that have altered expression in cancer. Genomics 95, 355–362 (2010).

    Article  CAS  PubMed  Google Scholar 

  97. Silva, J. M., Boczek, N. J., Berres, M. W., Ma, X. & Smith, D. I. LSINCT5 is over expressed in breast and ovarian cancer and affects cellular proliferation. RNA Biol. 8, 496–505 (2011).

    Article  CAS  PubMed  Google Scholar 

  98. Srikantan, V. et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. Proc. Natl Acad. Sci. USA 97, 12216–12221 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Chung, S. et al. Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci. 102, 245–252 (2011).

    Article  CAS  PubMed  Google Scholar 

  100. Yang, L. et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature 500, 598–602 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Prensner, J. R. et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat. Biotechnol. 29, 742–749 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Takayama, K. et al. Integration of cap analysis of gene expression and chromatin immunoprecipitation analysis on array reveals genome-wide androgen receptor signaling in prostate cancer cells. Oncogene 30, 619–630 (2011).

    Article  CAS  PubMed  Google Scholar 

  103. Takayama, K.-I. et al. Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. EMBO J. 32, 1665–1680 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Zhou, Y. et al. Activation of p53 by MEG3 non-coding RNA. J. Biol. Chem. 282, 24731–24742 (2007).

    Article  CAS  PubMed  Google Scholar 

  105. Gudmundsson, J. et al. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat. Genet. 41, 460–464 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gudmundsson, J. et al. Discovery of common variants associated with low TSH levels and thyroid cancer risk. Nat. Genet. 44, 319–322 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Jendrzejewski, J. et al. The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type. Proc. Natl Acad. Sci. USA 109, 8646–8651 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Yoon, H. et al. Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest. Int. J. Cancer 121, 767–775 (2007).

    Article  CAS  PubMed  Google Scholar 

  109. He, H. et al. A susceptibility locus for papillary thyroid carcinoma on chromosome 8q24. Cancer Res. 69, 625–631 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Kino, T., Hurt, D. E., Ichijo, T., Nader, N. & Chrousos, G. P. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci. Signal. 3, ra8 (2010).

    PubMed  PubMed Central  Google Scholar 

  111. Ding, Y. et al. In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features. Nature 505, 696–700 (2014).

    Article  CAS  PubMed  Google Scholar 

  112. Rouskin, S., Zubradt, M., Washietl, S., Kellis, M. & Weissman, J. S. Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo. Nature 505, 701–705 (2014).

    Article  CAS  PubMed  Google Scholar 

  113. Wan, Y. et al. Landscape and variation of RNA secondary structure across the human transcriptome. Nature 505, 706–709 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Kentwell, J., Gundara, J. S. & Sidhu, S. B. Noncoding RNAs in endocrine malignancy. Oncologist 19, 483–491 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Roy, M. et al. Analysis of the canine brain transcriptome with an emphasis on the hypothalamus and cerebral cortex. Mamm. Genome 24, 484–499 (2013).

    Article  CAS  PubMed  Google Scholar 

  116. Kim, K. et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 32, 1616–1625 (2013).

    Article  CAS  PubMed  Google Scholar 

  117. Xu, B. et al. Multiple roles for the non-coding RNA SRA in regulation of adipogenesis and insulin sensitivity. PLoS ONE 5, e14199 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Liu, S. et al. SRA gene knockout protects against diet-induced obesity and improves glucose tolerance. J. Biol. Chem. 289, 13000–13009 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sun, J., Lin, Y. & Wu, J. Long non-coding RNA expression profiling of mouse testis during postnatal development. PLoS ONE 8, e75750 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Li, L. et al. Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of colorectal cancer. J. Exp. Clin. Cancer Res. 32, 104 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

M.K. is supported by the fellowship Kn1106/1-1 from the German Research Foundation. H.F.L. is supported by NIH grants DK047618-25 and DK068348-07. L.S. is supported by National Research Foundation grant NRF-2011NRF-NRFF 001-025. The authors thank J. Alvarez-Dominguez for critical discussions.

Author information

Authors and Affiliations

Authors

Contributions

M.K. researched data for the article and wrote the article. All authors substantially contributed to discussing the content and reviewing and/or editing the manuscript before submission.

Corresponding author

Correspondence to Lei Sun.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Knoll, M., Lodish, H. & Sun, L. Long non-coding RNAs as regulators of the endocrine system. Nat Rev Endocrinol 11, 151–160 (2015). https://doi.org/10.1038/nrendo.2014.229

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2014.229

This article is cited by

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer