Long Non-Coding RNAs – Current Methods of Detection and Clinical Applications

Česká verzia

Authors: L. Moráňová; M. Bartošík
Authors place of work: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in the journal: Klin Onkol 2019; 32(Supplementum 3): 65-71
Category: Review
doi: https://doi.org/10.14735/amko20193S65

Summary

Background: Long non-coding RNAs (lncRNA) are more than 200-nucleotide-long RNA molecules that affect multiple physiologic phenomena and have important regulatory functions in cells. Their levels are often altered in various malignancies, thus they represent a potential biomarker for the diagnostics, prognosis or recurrence of cancer. Their importance has recently led to an enormous increase in a number of publications on the subject. The most frequently studied lncRNAs are HOTAIR, MALAT1 and PCA3.

Aim: Numerous methods are currently being developed for the analysis or detection of lncRNA. They are mostly based on optical methods used for the detection of messenger RNAs, including polymerase chain reaction with reverse transcription, fluorescence in situ hybridisation or next-generation sequencing, but caution must be taken due to their structural differences. Here, we describe not only standard but also novel techniques for lncRNA detection, including chemiluminescent and electrochemical techniques.

Conclusion: Despite the great progress and plethora of papers on this topic, there is only one single approved lncRNA-based diagnostic test, a PCA3 test for the diagnosis of prostate cancer from the patient’s urine. All other tests are only in their research phase and need to be validated. Nevertheless, lncRNA diagnostics offer enormous potential and thus it is highly probable that other diagnostic tests on different lncRNA types will soon appear.

Keywords:

Long non-coding RNA – tumor biomarkers – carcinogenesis – biosensing techniques

Zdroje

1. Weidle UH, Birzele F, Kollmorgen G et al. Long non-coding RNAs and their role in metastasis. Cancer Genom Proteom 2017; 14 (3): 143–160. doi: 10.21873/cgp.20027.

2. Mattick JS, Rinn JL. Discovery and annotation of long noncoding RNAs. Nat Struct Mol Biol 2015; 22 (1): 5–7. doi: 10.1038/nsmb.2942.

3. noncode.org. An integrated knowledge database dedicated to ncRNAs, especially lncRNAs. [online]. Available from: http: //www.noncode.org/.

4. LNCipedia. A comprehensive compendium of human long non-coding RNAs. [online]. Available from: https: //lncipedia.org/.

5. Volders PJ, Anckaert J, Verheggen K et al. LNCipedia 5: towards a reference set of human long non-coding RNAs. Nucleic Acid Res 2018; 47 (D1): D135–D139. doi: 10.1093/nar/gky1031.

6. Gibbons HR, Shaginurova G, Kim LC et al. Divergent lncRNA GATA3-AS1 regulates GATA3 transcription in T-helper 2 cells. Front Immunol 2018; 9: 2512. doi: 10.3389/fimmu.2018.02512.

7. Šána J, Faltejsková P, Svoboda M et al. Dlouhé nekódující RNA a jejich význam u nádorových onemocnění. Klin Onkol 2012; 25 (4): 246–254. doi: 10.14735/amko2012246.

8. Dykes IM, Emanueli C. Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genom Proteom Bioinform 2017; 15 (3): 177–186. doi: 10.1016/j.gpb.2016.12.005.

9. Gromesová B, Kubaczková V, Bollová B et al. Potenciál dlouhých nekódujících molekul RNA v diagnostice nádorových onemocnění. Klin Onkol 2016; 29 (1): 20–28. doi: 10.14735/amko201620.

10. Qi P, Zhou XY, Du X. Circulating long non-coding RNAs in cancer: current status and future perspectives. Mol Cancer 2016; 15 (1): 39. doi: 10.1186/s12943-016-0524-4.

11. Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell 2016; 29 (4): 452–463. doi: 10.1016/j.ccell.2016.03.010.

12. Sallam T, Sandhu J, Tontonoz P. Long noncoding RNA discovery in cardiovascular disease. Circul Res 2018; 122 (1): 155–166. doi: 10.1161/CIRCRESAHA.117.311802.

13. Luo Q, Chen Y. Long noncoding RNAs and Alzheimer’s disease. Clin Interv Aging 2016; 11: 867–872. doi: 10.2147/CIA.S107037.

14. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100 (1): 57–70. doi: 10.1016/s0092-8674 (00) 81683-9.

15. Hanahan D, Weinberg Robert A. Hallmarks of cancer: the next generation. Cell 2011; 144 (5): 646–674. doi: 10.1016/j.cell.2011.02.013.

16. de Oliveira JC, Oliveira LC, Mathias C et al. Long non-coding RNAs in cancer: Another layer of complexity. J Gene Med 2019; 21 (1): e3065. doi: 10.1002/jgm.3065.

17. Bhan A, Mandal SS. LncRNA HOTAIR: a master regulator of chromatin dynamics and cancer. Biochim Biophys Acta 2015; 1856 (1): 151–164. doi: 10.1016/j.bbcan.2015.07.001.

18. Gupta RA, Shah N, Wang KC et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010; 464 (7291): 1071–1076. doi: 10.1038/nature08975.

19. Avazpour N, Hajjari M, Tahmasebi Birgani M. HOTAIR: a promising long non-coding RNA with potential role in breast invasive carcinoma. Front Genet 2017; 8: 170. doi: 10.3389/fgene.2017.00170.

20. Luo ZF, Zhao D, Li XQ et al. Clinical significance of HOTAIR expression in colon cancer. World J Gastroenterol 2016; 22 (22): 5254–5259. doi: 10.3748/wjg.v22.i22.5254.

21. Yang SZ, Xu F, Zhou T et al. The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand. J Biol Chem 2017; 292 (25): 10390–10397. doi: 10.1074/jbc.M117.786830.

22. Liu S, Lei H, Luo F et al. The effect of lncRNA HOTAIR on chemoresistance of ovarian cancer through regulation of HOXA7. Biol Chem 2018; 399 (5): 485–497. doi: 10.1515/hsz-2017-0274.

23. Zhang A, Zhao JC, Kim J et al. LncRNA HOTAIR enhances the androgen-receptor-mediated transcriptional program and drives castration-resistant prostate cancer. Cell Rep 2015; 13 (1): 209–221. doi: 10.1016/j.celrep.2015.08.069.

24. Xiao Z, Qu Z, Chen Z et al. LncRNA HOTAIR is a prognostic biomarker for the proliferation and chemoresistance of colorectal cancer via miR-203a-3p-mediated wnt/ß-catenin signaling pathway. Cell Physiol Biochem 2018; 46 (3): 1275–1285. doi: 10.1159/000489110.

25. Wright CM. Long noncoding RNAs and cancer. In: Gray SG (ed). Epigenetic Cancer Therapy. Boston: Academic Press 2015: 91–114.

26. Lu Y, Madu C. Prostate cancer biomarkers. In: Gupta RC (ed). Biomarkers in Toxicology. Boston: Academic Press 2014: 771–783.

27. de Kok JB, Verhaegh GW, Roelofs RW et al. DD3 (PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 2002; 62 (9): 2695–2698.

28. Bussemakers MJG, van Bokhoven A, Verhaegh GW et al. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 1999; 59 (23): 5975–5979.

29. Taille Adl, Irani J, Graefen M et al. Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol 2011; 185 (6): 2119–2125. doi: 10.1016/j.juro.2011.01.075.

30. Gutschner T, Hämmerle M, Eissmann M et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 2013; 73 (3): 1180–1189. doi: 10.1158/0008-5472.CAN-12-2850.

31. Wang X, Li M, Wang Z et al. Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 2015; 290 (7): 3925–3935. doi: 10.1074/jbc.M114.596866.

32. Tripathi V, Shen Z, Chakraborty A et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet 2013; 9 (3): e1003368. doi: 10.1371/journal.pgen.1003368.

33. Ying L, Chen Q, Wang Y et al. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst 2012; 8 (9): 2289–2294. doi: 10.1039/c2mb25070e.

34. Wu XS, Wang XA, Wu WG et al. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther 2014; 15 (6): 806–814. doi: 10.4161/cbt.28584.

35. Hu L, Wu Y, Tan D et al. Up-regulation of long noncoding RNA MALAT1 contributes to proliferation and metastasis in esophageal squamous cell carcinoma. J Exp Clin Canc Res 2015; 34 (1): 7. doi: 10.1186/s13046-015-0123-z.

36. Ma KX, Wang HJ, Li XR et al. Long noncoding RNA MALAT1 associates with the malignant status and poor prognosis in glioma. Tumour Biol 2015; 36 (5): 3355–3359. doi: 10.1007/s13277-014-2969-7.

37. Tian X, Xu G. Clinical value of lncRNA MALAT1 as a prognostic marker in human cancer: systematic review and meta-analysis. BMJ Open 2015; 5 (9): e008653. doi: 10.1136/bmjopen-2015-008653.

38. Kim J, Piao HL, Kim BJ et al. Long noncoding RNA MALAT1 suppresses breast cancer metastasis. Nat Genet 2018; 50 (12): 1705–1715. doi: 10.1038/s41588-018-0252-3.

39. Oliva-Rico D, Herrera LA. Regulated expression of the lncRNA TERRA and its impact on telomere biology. Mech Age Develop 2017; 167: 16–23. doi: 10.1016/j.mad.2017.09.001.

40. Sampl S, Pramhas S, Stern C et al. Expression of telomeres in astrocytoma WHO grade 2 to 4: TERRA level correlates with telomere length, telomerase activity, and advanced clinical grade. Transl Oncol 2012; 5 (1): 56–65. doi: 10.1593/tlo.11202.

41. Cusanelli E, Chartrand P. Telomeric repeat-containing RNA TERRA: a noncoding RNA connecting telomere biology to genome integrity. Front Genet 2015; 6: 143. doi: 10.3389/fgene.2015.00143.

42. Durand X, Moutereau S, Xylinas E et al. Progensa™ PCA3 test for prostate cancer. Exp Rev Mol Diagn 2011; 11 (2): 137–144. doi: 10.1586/erm.10.122.

43. MyBioSource.com. PCA3 elisa kit: human prostate cancer antigen 3 (PCA3) ELISA kit. [online]. Available from: https: //www.mybiosource.com/pca3-human-elisa-kits/prostate-cancer-antigen-3-pca3/109022.

44. Yang Q, Wan Q, Zhang L et al. Analysis of LncRNA expression in cell differentiation. RNA Biol 2018; 15 (3): 413–422. doi: 10.1080/15476286.2018.1441665.

45. Novogene.com. lncRNA SEQUENCING. [online]. Available from: https: //en.novogene.com/next-generation-sequencing-services/gene-regulation/lncrna-sequencing/.

46. sequencing.roche.com. SeqCap lncRNA Probes. [online]. Available from: https: //sequencing.roche.com/en/products-solutions/by-category/target-enrichment/hybridization/seqcap-lncrna.html.

47. illumina.com. rRNA & Globin mRNA removal kit selection guide. [online]. Available from: https: //www.illumina.com/products/selection-tools/rrna-depletion-selection-guide.html.

48. bio-rad.com. lncRNA RT-qPCR workflow. [online]. Available from: http: //www.bio-rad.com/en-cz/category/lncrna-rt-qpcr-workflow?ID=OUJ92R15.

49. Coassin SR, Orjalo AV, Semaan SJ et al. Simultaneous detection of nuclear and cytoplasmic RNA variants utilizing Stellaris^® RNA fluorescence in situ hybridization in adherent cells. In: Nielsen BS (ed). In Situ Hybridization Protocols. New York: Springer 2014: 189–199.

50. Islam MN, Moriam S, Umer M et al. Naked-eye and electrochemical detection of isothermally amplified HOTAIR long non-coding RNA. Analyst 2018; 143 (13): 3021–3028. doi: 10.1039/c7an02109g.

51. Liu F, Li T, Zhang L et al. PAMAM/polyhedral nanogold-modified probes with DNAase catalysis for the amperometric electrochemical detection of metastasis-associated lung adenocarcinoma transcript 1. J Biol Eng 2019; 13 (1): 21. doi: 10.1186/s13036-019-0149-4.

52. Kim T, Cui R, Jeon YJ et al. Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proc Natl Acad Sci USA 2014; 111 (11): 4173–4178. doi: 10.1073/pnas.1400350111.

53. Léveillé N, Melo CA, Rooijers K et al. Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA. Nat Commun 2015; 6: 6520. doi: 10.1038/ncomms7520.

54. Lian Y, Yan C, Xu H et al. A novel lncRNA, LINC00460, affects cell proliferation and apoptosis by regulating KLF2 and CUL4A expression in colorectal cancer. Mol Ther Nucl Acid 2018; 12: 684–697. doi: 10.1016/ j.omtn.2018.06.012.

55. Zhao J, Du P, Cui P et al. LncRNA PVT1 promotes angiogenesis via activating the STAT3/VEGFA axis in gastric cancer. Oncogene 2018; 37 (30): 4094–4109. doi: 10.1038/s41388-018-0250-z.

56. Munschauer M, Nguyen CT, Sirokman K et al. The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature 2018; 561 (7721): 132–136. doi: 10.1038/s41586-018-0453-z.

57. Huang D, Chen J, Yang L et al. NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death. Nat Immunol 2018; 19 (10): 1112–1125. doi: 10.1038/s41590-018-0207-y.

58. Zhang X, Rice K, Wang Y et al. Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions. Endo-crinology 2010; 151 (3): 939–947. doi: 10.1210/en.2009-0657.

59. Svoboda M, Slyskova J, Schneiderova M et al. HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. Carcinogenesis 2014; 35 (7): 1510–1515. doi: 10.1093/carcin/bgu055.

60. Li X, Wu Z, Mei Q et al. Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma. Br J Cancer 2013; 109 (8): 2266–2278. doi: 10.1038/bjc.2013.548.

61. Okugawa Y, Toiyama Y, Hur K et al. Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. Carcinogenesis 2014; 35 (12): 2731–2739. doi: 10.1093/carcin/bgu200.

62. Guo W, Dong Z, Bai Y et al. Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumor Biol 2015; 36 (4): 2845–2854. doi: 10.1007/s13277-014-2912-y.

63. Crawford ED, Rove KO, Trabulsi EJ et al. Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases. J Urol 2012; 188 (5): 1726–1731. doi: 10.1016/j.juro.2012.07.023.

64. Roobol MJ, Schröder FH, van Leeuwen P et al. 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 2010; 58 (4): 475–481. doi: 10.1016/j.eururo.2010.06. 039.

65. Ochiai A, Okihara K, Kamoi K et al. Clinical utility of the prostate cancer gene 3 (PCA3) urine assay in Japanese men undergoing prostate biopsy. BJU Int 2013; 111 (6): 928–933. doi: 10.1111/j.1464-410X.2012.11683.x.

66. Ji P, Diederichs S, Wang W et al. MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 2003; 22 (39): 8031–8041. doi: 10.1038/sj.onc.1206928.

67. Wang Z, Katsaros D, Biglia N et al. High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival. Breast Cancer Res Treat 2018; 171 (2): 261–271. doi: 10.1007/s10549-018-4839-2.