Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

An emerging understanding of long noncoding RNAs in kidney cancer

  • 1325 Accesses

  • 73 Citations



Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis.


An electronic search of all relevant publications in peer-reviewed journals before April 2014 was performed on PubMed, Google scholar databases. The keywords of long-coding RNAs, lncRNAs, kidney tumor, renal cancers were used for searching.


The lncRNA biology was introduced into cancer biology from contemporary research, and the regulatory mechanisms of lncRNAs was highlighted at transcriptional, post-transcriptional and epigenetic levels. The kidney cancer-associated onco-lncRNAs (e.g., KCQN1OT1, MALAT-1 and HOTAIT) and tumor suppressive lncRNAs (e.g., H19, GAS5 and MEG3) were summarized and their possible regulatory network was depicted in a comprehensive diagram.


LncRNAs are deregulated in various cancers including kidney cancer, demonstrating both oncogenic and tumor suppressive roles, thus suggesting their aberrant expression may be a substantial contributor in cancer development. LncRNAs could serve as potential diagnostics biomarkers and/or therapeutic targets.

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

Fig. 1
Fig. 2
Fig. 3


  1. Bertozzi D, Iurlaro R, Sordet O, Marinello J, Zaffaroni N, Capranico G (2011) Characterization of novel antisense HIF-1alpha transcripts in human cancers. Cell Cycle 10:3189–3197

  2. Brito GC, Fachel AA, Vettore AL et al (2008) Identification of protein-coding and intronic noncoding RNAs down-regulated in clear cell renal carcinoma. Mol Carcinog 47:757–767

  3. Bussemakers MJ, van Bokhoven A, Verhaegh GW et al (1999) DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 59:5975–5979

  4. Cabili MN, Trapnell C, Goff L et al (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927

  5. Chiesa N, De Crescenzo A, Mishra K et al (2012) The KCNQ1OT1 imprinting control region and non-coding RNA: new properties derived from the study of Beckwith–Wiedemann syndrome and Silver–Russell syndrome cases. Hum Mol Genet 21:10–25

  6. Chiyomaru T, Fukuhara S, Saini S et al (2014) Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells. J Biol Chem 289(18):12550–12565

  7. Davis IJ, Hsi BL, Arroyo JD et al (2003) Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. Proc Natl Acad Sci USA 100:6051–6056

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

  9. Durand X, Xylinas E, Radulescu C et al (2012) The value of urinary prostate cancer gene 3 (PCA3) scores in predicting pathological features at radical prostatectomy. BJU Int 110:43–49

  10. Fachel AA, Tahira AC, Vilella-Arias SA et al (2013) Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations. Mol Cancer 12:140

  11. Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15:7–21

  12. Frevel MA, Sowerby SJ, Petersen GB, Reeve AE (1999) Methylation sequencing analysis refines the region of H19 epimutation in Wilms tumor. J Biol Chem 274:29331–29340

  13. Geng YJ, Xie SL, Li Q, Ma J, Wang GY (2011) Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res 39:2119–2128

  14. Gudmundsson J, Sulem P, Gudbjartsson DF et al (2013) A common variant at 8q24.21 is associated with renal cell cancer. Nat Commun 4:2776

  15. Gupta RA, Shah N, Wang KC et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

  16. Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719

  17. Gutschner T, Hammerle M, Eissmann M et al (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73(3):1180–1189

  18. Ji P, Diederichs S, Wang W et al (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22:8031–8041

  19. Jonasch E, Futreal PA, Davis IJ et al (2012) State of the science: an update on renal cell carcinoma. Mol Cancer Res 10:859–880

  20. Kawakami T, Chano T, Minami K, Okabe H, Okada Y, Okamoto K (2006) Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. Hum Mol Genet 15:821–830

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

  22. Kogo R, Shimamura T, Mimori K et al (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71:6320–6326

  23. Kuiper RP, Schepens M, Thijssen J et al (2003) Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution. Hum Mol Genet 12:1661–1669

  24. Maher ER (2013) Genomics and epigenomics of renal cell carcinoma. Semin Cancer Biol 23:10–17

  25. Mercer TR, Qureshi IA, Gokhan S et al (2010) Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. BMC Neurosci 11:14

  26. Nakada C, Tsukamoto Y, Matsuura K et al (2011) Overexpression of miR-210, a downstream target of HIF1alpha, causes centrosome amplification in renal carcinoma cells. J Pathol 224:280–288

  27. Ozgur E, Mert U, Isin M, Okutan M, Dalay N, Gezer U (2013) Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells. Clin Exp Med 13(2):119–126

  28. Panzitt K, Tschernatsch MM, Guelly C et al (2007) Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology 132:330–342

  29. Ploussard G, Durand X, Xylinas E et al (2011) Prostate cancer antigen 3 score accurately predicts tumour volume and might help in selecting prostate cancer patients for active surveillance. Eur Urol 59:422–429

  30. Prensner JR, Chinnaiyan AM (2011) The emergence of lncRNAs in cancer biology. Cancer Discov 1:391–407

  31. Qiao HP, Gao WS, Huo JX, Yang ZS (2013) Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev 14:1077–1082

  32. Ricketts CJ, Hill VK, Linehan WM (2014) Tumor-specific hypermethylation of epigenetic biomarkers, including SFRP1, predicts for poorer survival in patients from the tcga kidney renal clear cell carcinoma (KIRC) project. PLoS ONE 9:e85621

  33. Rini BI, Campbell SC, Escudier B (2009) Renal cell carcinoma. Lancet 373:1119–1132

  34. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166

  35. Roobol MJ, Schroder FH, van Leenders GL et al (2010a) Performance of prostate cancer antigen 3 (PCA3) and prostate-specific antigen in Prescreened men: reproducibility and detection characteristics for prostate cancer patients with high PCA3 scores (≥100). Eur Urol 58:893–899

  36. Roobol MJ, Schroder FH, van Leeuwen P et al (2010b) Performance of the prostate cancer antigen 3 (PCA3) gene and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test. Eur Urol 58:475–481

  37. Rydzanicz M, Wrzesinski T, Bluyssen HA, Wesoly J (2013) Genomics and epigenomics of clear cell renal cell carcinoma: recent developments and potential applications. Cancer Lett 341:111–126

  38. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

  39. Simon JM, Hacker KE, Singh D et al (2014) Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects. Genome Res 24:241–250

  40. Thrash-Bingham CA, Tartof KD (1999) aHIF: a natural antisense transcript overexpressed in human renal cancer and during hypoxia. J Natl Cancer Inst 91:143–151

  41. van Asseldonk M, Schepens M, de Bruijn D, Janssen B, Merkx G, van Geurts Kessel A (2000) Construction of a 350-kb sequence-ready 11q13 cosmid contig encompassing the markers D11S4933 and D11S546: mapping of 11 genes and 3 tumor-associated translocation breakpoints. Genomics 66:35–42

  42. Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol 21:354–361

  43. Wu W (2010) MicroRNA and cancer, 2011 edn. Humana Press, New York

  44. Wu W, Chan JA (2013) Understanding the role of long noncoding RNAs in the cancer genome. In: Wu W, Choudhry H (eds) Next generation sequencing in cancer research-decoding cancer genome, 1st edn. Springer, New York, pp 199–215

  45. Yu G, Yao W, Wang J et al (2012) LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray. PLoS ONE 7:e42377

Download references


This work was supported, in part, by the National Natural Science Foundation of China (81371611, 81171391, 81372743) and the National Basic Research Priorities Program 973 Project (2014CB744504) from the Ministry of Science and Technology of China. We apologize to those whose research we could not cite due to the limitations of our topic and space.

Conflict of interest


Author information

Correspondence to Zhengyu Zhang.

Additional information

Shuigen Zhou and Jiandong Wang have contributed equally to this work.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhou, S., Wang, J. & Zhang, Z. An emerging understanding of long noncoding RNAs in kidney cancer. J Cancer Res Clin Oncol 140, 1989–1995 (2014).

Download citation


  • Long noncoding RNAs
  • LncRNAs
  • Kidney cancer
  • Renal cell carcinoma