Skip to main content

Advertisement

SpringerLink
Log in

ANRIL: a pivotal tumor suppressor long non-coding RNA in human cancers

  • Review
  • Published:
Tumor Biology

Abstract

Long non-coding RNAs (lncRNAs) are a family of non-protein-coding RNAs with length more than 200 nucleotides. LncRNAs played important roles in many biological processes such as cell development, proliferation, invasion and migration. Deregulation of LncRNAs was found in multiple tumors where they can act as a tumor suppressor gene or oncogene. LncRNA ANRIL was identified as an oncogene involved in a number of tumors such as gastric cancer, lung cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma. Inhibition of ANRIL suppressed the cancer cell proliferation, migration and invasion. Increasing data has showed that ANRIL may act as a diagnostic and prognostic biomarker for some tumors. In our review, we summarize an overview of current knowledge concerning the expression and role of ANRIL in various cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wan X, Ding X, Chen S, Song H, Jiang H, Fang Y, et al. The functional sites of miRNAs and lncRNAs in gastric carcinogenesis. Tumour Biol. 2015;36:521–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tano K, Akimitsu N. Long non-coding RNAs in cancer progression. Front Genet. 2012;3:219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013;45:1895–910.

    Article  CAS  PubMed  Google Scholar 

  5. Kitagawa M, Kotake Y, Ohhata T. Long non-coding RNAs involved in cancer development and cell fate determination. Curr Drug Targets. 2012;13:1616–21.

    Article  CAS  PubMed  Google Scholar 

  6. Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9:703–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Taylor DH, Chu ET, Spektor R, Soloway PD. Long non-coding RNA regulation of reproduction and development. Mol Reprod Dev. 2015. doi:10.1002/mrd.22581.

  8. Yang Y, Wen L, Zhu H. Unveiling the hidden function of long non-coding RNA by identifying its major partner-protein. Cell Biosci. 2015;5:59.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yu X, Li Z. The role of miRNAs in cutaneous squamous cell carcinoma. J Cell Mol Med. 2015. doi:10.1111/jcmm.12649.

  10. Li Z, Yu X, Shen J. The role of miRNAs in the pheochromocytomas. Tumour Biol. 2015. doi:10.1007/s13277-015-4199-z.

  11. Yu X, Li Z. MicroRNA expression and its implications for diagnosis and therapy of tongue squamous cell carcinoma. J Cell Mol Med. 2015. doi:10.1111/jcmm.12650.

  12. Li Z, Yu X, Shen J, Jiang Y. MicroRNA dysregulation in uveal melanoma: a new player enters the game. Oncotarget. 2015;6:4562–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yu X, Li Z. Long non-coding RNA growth arrest-specific transcript 5 in tumor biology. Oncol Lett. 2015;10:1953–8.

    PubMed  PubMed Central  Google Scholar 

  14. Yu X, Li Z. Long non-coding RNA HOTAIR: a novel oncogene (review). Mol Med Rep. 2015;12:5611–8.

    CAS  PubMed  Google Scholar 

  15. Silva A, Bullock M, Calin G. The clinical relevance of long non-coding RNAs in cancer. Cancers. 2015;7:2169–82.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang G, Liu C, Deng S, Zhao Q, Li T, Qiao S, et al. Long noncoding rnas in regulation of human breast cancer. Brief Funct Genomics. 2015. doi:10.1093/bfgp/elv049.

  17. Tao H, Yang JJ, Zhou X, Deng ZY, Shi KH, Li J. Emerging role of long non-coding RNAs in lung cancer: current status and future prospects. Respir Med. 2015;110:12–9. 

  18. Meseure D, Drak Alsibai K, Nicolas A, Bieche I, Morillon A. Long non-coding RNAs as new architects in cancer epigenetics, prognostic biomarkers, and potential therapeutic targets. Biomed Res Int. 2015;2015:320214.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Shahryari A, Jazi MS, Samaei NM, Mowla SJ. Long non-coding RNA SOX2OT: expression signature, splicing patterns, and emerging roles in pluripotency and tumorigenesis. Front Genet. 2015;6:196.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ding X, Wan X, Jiang H, Song H, Fang Y, Chen S, et al. The clinical value of ncRNAs in gastric cancer: a systematic review and meta-analyses. Tumour Biol. 2015;36:4017–25.

    Article  PubMed  Google Scholar 

  21. Hajjari M, Salavaty A. HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med. 2015;12:1–9.

    PubMed  PubMed Central  Google Scholar 

  22. Yang X, Xie X, Xiao YF, Xie R, Hu CJ, Tang B, et al. The emergence of long non-coding RNAs in the tumorigenesis of hepatocellular carcinoma. Cancer Lett. 2015;360:119–24.

    Article  CAS  PubMed  Google Scholar 

  23. Martens-Uzunova ES, Bottcher R, Croce CM, Jenster G, Visakorpi T, Calin GA. Long non-coding RNA in prostate, bladder, and kidney cancer. Eur Urol. 2014;65:1140–51.

    Article  CAS  PubMed  Google Scholar 

  24. Yarmishyn AA, Kurochkin IV. Long non-coding RNAs: a potential novel class of cancer biomarkers. Front Genet. 2015;6:145.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Di Gesualdo F, Capaccioli S, Lulli M. A pathophysiological view of the long non-coding RNA world. Oncotarget. 2014;5:10976–96.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense non-coding RNA whose expression coclusters with ARF. Cancer Res. 2007;67:3963–9.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, et al. Long non-coding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of mir-99a/mir-449a. Oncotarget. 2014;5:2276–92.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Iranpour M, Soudyab M, Geranpayeh L, Mirfakhraie R, Azargashb E, Movafagh A, et al. Expression analysis of four long non-coding RNAs in breast cancer. Tumour Biol. 2015. doi:10.1007/s13277-015-4135-2.

  29. Naemura M, Murasaki C, Inoue Y, Okamoto H, Kotake Y. Long non-coding RNA ANRIL regulates proliferation of non-small-cell lung cancer and cervical cancer cells. Anticancer Res. 2015;35:5377–82.

    CAS  PubMed  Google Scholar 

  30. Zhu H, Li X, Song Y, Zhang P, Xiao Y, Xing Y. Long non-coding RNA ANRIL is upregulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway. Biochem Biophys Res Commun. 2015;467:223–8.

    Article  CAS  PubMed  Google Scholar 

  31. Kia SK, Gorski MM, Giannakopoulos S, Verrijzer CP. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus. Mol Cell Biol. 2008;28:3457–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gil J, Peters G. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol. 2006;7:667–77.

    Article  CAS  PubMed  Google Scholar 

  33. Ozenne P, Eymin B, Brambilla E, Gazzeri S. The ARF tumor suppressor: structure, functions and status in cancer. Int J Cancer. 2010;127:2239–47.

    Article  CAS  PubMed  Google Scholar 

  34. Kheradmand Kia S, Solaimani Kartalaei P, Farahbakhshian E, Pourfarzad F, von Lindern M, Verrijzer CP. EZH2-dependent chromatin looping controls INK4a and INK4b, but not ARF, during human progenitor cell differentiation and cellular senescence. Epigenetics Chromatin. 2009;2:16.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, et al. Molecular interplay of the non-coding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010;38:662–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Aguilo F, Di Cecilia S, Walsh MJ. Long non-coding RNA ANRIL and polycomb in human cancers and cardiovascular disease. Curr Top Microbiol Immunol. 2015. doi:10.1007/82_2015_455.

  37. He S, Gu W, Li Y, Zhu H. ANRIL/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians. BMC Evol Biol. 2013;13:247.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Aguilo F, Zhou MM, Walsh MJ. Long non-coding RNA, polycomb, and the ghosts haunting INK4b-ARF-INK4a expression. Cancer Res. 2011;71:5365–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, et al. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4b) tumor suppressor gene. Oncogene. 2011;30:1956–62.

    Article  CAS  PubMed  Google Scholar 

  40. Rodriguez C, Borgel J, Court F, Cathala G, Forne T, Piette J. CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus. Biochem Biophys Res Commun. 2010;392:129–34.

    Article  CAS  PubMed  Google Scholar 

  41. Nie FQ, Sun M, Yang JS, Xie M, Xu TP, Xia R, et al. Long non-coding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and p21 expression. Mol Cancer Ther. 2015;14:268–77.

    Article  CAS  PubMed  Google Scholar 

  42. Lin L, Gu ZT, Chen WH, Cao KJ. Increased expression of the long non-coding RNA ANRIL promotes lung cancer cell metastasis and correlates with poor prognosis. Diagn Pathol. 2015;10:14.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kang YH, Kim D, Jin EJ. Down-regulation of phospholipase d stimulates death of lung cancer cells involving upregulation of the long ncRNA anril. Anticancer Res. 2015;35:2795–803.

    CAS  PubMed  Google Scholar 

  44. Huang MD, Chen WM, Qi FZ, Xia R, Sun M, Xu TP, et al. Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of klf2. J Hematol Oncol. 2015;8:50.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Hua L, Wang CY, Yao KH, Chen JT, Zhang JJ, Ma WL. High expression of long non-coding RNA ANRIL is associated with poor prognosis in hepatocellular carcinoma. Int J Clin Exp Pathol. 2015;8:3076–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen D, Zhang Z, Mao C, Zhou Y, Yu L, Yin Y, et al. ANRIL inhibits p15(INK4b) through the TGF beta 1 signaling pathway in human esophageal squamous cell carcinoma. Cell Immunol. 2014;289:91–6.

    Article  CAS  PubMed  Google Scholar 

  47. Kang M, Sang Y, Gu H, Zheng L, Wang L, Liu C, et al. Long non-coding RNAs POLR2Ee rs3787016 c/t and HULC rs7763881 A/C polymorphisms are associated with decreased risk of esophageal cancer. Tumour Biol. 2015;36:6401–8.

    Article  CAS  PubMed  Google Scholar 

  48. Martinez-Fernandez M, Feber A, Duenas M, Segovia C, Rubio C, Fernandez M, et al. Analysis of the polycomb-related lncRNAs HOTAIR and ANRIL in bladder cancer. Clin Epigenetics. 2015;7:109.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Qiu JJ, Lin YY, Ding JX, Feng WW, Jin HY, Hua KQ. Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer. Int J Oncol. 2015;46:2497–505.

    CAS  PubMed  Google Scholar 

  50. Iacobucci I, Sazzini M, Garagnani P, Ferrari A, Boattini A, Lonetti A, et al. A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia. Leuk Res. 2011;35:1052–9.

    Article  CAS  PubMed  Google Scholar 

  51. Pasmant E, Sabbagh A, Masliah-Planchon J, Ortonne N, Laurendeau I, Melin L, et al. Role of non-coding RNA ANRIL in genesis of plexiform neurofibromas in neurofibromatosis type 1. J Natl Cancer Inst. 2011;103:1713–22.

    Article  CAS  PubMed  Google Scholar 

  52. Mussotter T, Kluwe L, Hogel J, Nguyen R, Cooper DN, Mautner VF, et al. Non-coding RNA ANRIL and the number of plexiform neurofibromas in patients with NF1 microdeletions. BMC Med Genet. 2012;13:98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (Grant Numbers: 81401847, 81272053 and 81330044).

Author information

Author notes

    Authors and Affiliations

    1. Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

      Zheng Li & Jianxiong Shen

    2. Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

      Xin Yu

    Authors
    1. Zheng Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xin Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Jianxiong Shen
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Jianxiong Shen.

    Ethics declarations

    Conflicts of interest

    None

    Additional information

    Zheng Li and Xin Yu contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Li, Z., Yu, X. & Shen, J. ANRIL: a pivotal tumor suppressor long non-coding RNA in human cancers. Tumor Biol. 37, 5657–5661 (2016). https://doi.org/10.1007/s13277-016-4808-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-016-4808-5

    Keywords

    Search

    Navigation