Advertisement

Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers

Published:April 06, 2017DOI:https://doi.org/10.1016/j.trsl.2017.03.005
      Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer. Although lncRNAs have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless, a growing body of evidence suggests that several lncRNAs expression profiles in bladder malignancies are associated with poor prognosis, and they can be detected in biological fluids, such as urines. Here, we review current progress in the biology and the implication of lncRNAs associated with bladder cancer, and we discuss their potential use as diagnosis and prognosis biomarkers in bladder malignancies with a focus on their role in high-risk nonmuscle-invasive tumors.

      Abbreviations:

      BlCa (bladder cancer), BTA (bladder tumor antigen), circRNAs (circular RNA), FDA (United States of America's Food and Drug Administration), FDP (fibrin degradation product), FISH (fluorescent in situ hybridization), GAS-5 (growth arrest-specific 5), GHET 1 (gastric carcinoma highly expressed transcript 1), HGMI (high-grade muscle invasive tumors), ImmunoCyt (immunocytometry), ISH (in situ hybridization), ISUP (International Society of Urological Pathology criteria), Linc-UBC1 (upregulated in bladder cancer 1), lncRNAs (long noncoding RNAs), MALAT-1 (metastasis-associated lung adenocarcinoma transcript 1), MEG3 (maternally expressed gene 3), miRNAs (microRNAs), mRNA (RNA mature), NBE (normal bladder epithelium), ncRAN (noncoding RNA expressed in aggressive neuroblastoma), ncRNAs (noncoding RNA), NEAT 1 (nuclear paraspeckle assembly transcript 1), NMIBC (nonmuscle-invasive bladder cancer), NMP22 (nuclear mitotic apparatus), PBS (phosphate buffered saline), PCAT-1 (prostate cancer–associated transcript 1), PCR (polymerase chain reaction), PSA (prostate-specific antigen), PUNLMP (papillary urothelial neoplasm of low malignant potential), PVT-1 (plasmacytoma variant translocation gene lncRNA), qRT-PCR (quantitative real-time polymerase chain reaction), RIP (RNA immunoprecipitation), RNA-Seq (RNA sequencing), shRNA (small hairpin RNA), SNHG16 (snoRNA host gene 16), SPRY4-IT1 (protein sprouty homolog 4 lncRNA), TCC (transitional cell carcinoma), TNM (tumor-node-metastasis), T-UCRs (transcribed ultraconserved regions), TUG1 (taurine-upregulated gene 1), UBC (urinary bladder cancer), UBC1 (upregulated in bladder cancer 1), UCA1 (urothelial cancer associated-1), UCRs (ultraconserved regions), UEs (urinary exosomes), UNMIBC (upregulated in nonmuscle-invasive bladder cancer), WHO (World Health Organization)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Burger M.
        • Catto J.W.
        • Dalbagni G.
        • et al.
        Epidemiology and risk factors of urothelial bladder cancer.
        Eur Urol. 2013; 63: 234-241
        • Babjuk M.
        • Oosterlinck W.
        • Sylvester R.
        • et al.
        EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update.
        Eur Urol. 2011; 59: 997-1008
        • Witjes J.A.
        • Hendricksen K.
        Intravesical pharmacotherapy for non-muscle-invasive bladder cancer: a critical analysis of currently available drugs, treatment schedules, and long-term results.
        Eur Urol. 2008; 53: 45-52
        • Lotan Y.
        • Roehrborn C.G.
        Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses.
        Urology. 2003; 61 (discussion 18): 109-118
        • Oude Elferink P.
        • Witjes J.A.
        Blue-light cystoscopy in the evaluation of non-muscle-invasive bladder cancer.
        Ther Adv Urol. 2014; 6: 25-33
        • Daniltchenko D.I.
        • Riedl C.R.
        • Sachs M.D.
        • et al.
        Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study.
        J Urol. 2005; 174 (discussion 33): 2129-2133
        • Denzinger S.
        • Burger M.
        • Walter B.
        • et al.
        Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid-induced fluorescence diagnosis: 8-year results of prospective randomized study.
        Urology. 2007; 69: 675-679
        • Sievert K.D.
        • Amend B.
        • Nagele U.
        • et al.
        Economic aspects of bladder cancer: what are the benefits and costs?.
        World J Urol. 2009; 27: 295-300
        • Svatek R.S.
        • Hollenbeck B.K.
        • Holmang S.
        • et al.
        The economics of bladder cancer: costs and considerations of caring for this disease.
        Eur Urol. 2014; 66: 253-262
        • Audas T.E.
        • Lee S.
        Stressing out over long noncoding RNA.
        Biochim Biophys Acta. 2016; 1859: 184-191
        • Berrondo C.
        • Flax J.
        • Kucherov V.
        • et al.
        Expression of the long non-coding RNA HOTAIR correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes.
        PLoS One. 2016; 11: e0147236
        • Han Y.
        • Liu Y.
        • Gui Y.
        • Cai Z.
        Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder.
        J Surg Oncol. 2013; 107: 555-559
        • Fan Y.
        • Shen B.
        • Tan M.
        • et al.
        TGF-beta-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12.
        Clin Cancer Res. 2014; 20: 1531-1541
        • Luo M.
        • Li Z.
        • Wang W.
        • Zeng Y.
        • Liu Z.
        • Qiu J.
        Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expression.
        FEBS J. 2013; 280: 1709-1716
        • Derrien T.
        • Johnson R.
        • Bussotti G.
        • et al.
        The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.
        Genome Res. 2012; 22: 1775-1789
        • Khalil A.M.
        • Guttman M.
        • Huarte M.
        • et al.
        Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.
        Proc Natl Acad Sci U S A. 2009; 106: 11667-11672
        • Rinn J.L.
        • Chang H.Y.
        Genome regulation by long noncoding RNAs.
        Annu Rev Biochem. 2012; 81: 145-166
        • Sigova A.A.
        • Mullen A.C.
        • Molinie B.
        • et al.
        Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells.
        Proc Natl Acad Sci U S A. 2013; 110: 2876-2881
        • Nagano T.
        • Fraser P.
        No-nonsense functions for long noncoding RNAs.
        Cell. 2011; 145: 178-181
        • Derrien T.
        • Guigo R.
        • Johnson R.
        The long non-coding RNAs: a new (P)layer in the “Dark Matter”.
        Front Genet. 2011; 2: 107
        • Kapranov P.
        • Cheng J.
        • Dike S.
        • et al.
        RNA maps reveal new RNA classes and a possible function for pervasive transcription.
        Science. 2007; 316: 1484-1488
        • Wang K.C.
        • Chang H.Y.
        Molecular mechanisms of long noncoding RNAs.
        Mol Cell. 2011; 43: 904-914
        • Cabili M.N.
        • Trapnell C.
        • Goff L.
        • et al.
        Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses.
        Genes Dev. 2011; 25: 1915-1927
        • Bejerano G.
        • Pheasant M.
        • Makunin I.
        • et al.
        Ultraconserved elements in the human genome.
        Science. 2004; 304: 1321-1325
        • Guttman M.
        • Amit I.
        • Garber M.
        • et al.
        Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
        Nature. 2009; 458: 223-227
        • Huarte M.
        • Guttman M.
        • Feldser D.
        • et al.
        A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
        Cell. 2010; 142: 409-419
        • Karapetyan A.R.
        • Buiting C.
        • Kuiper R.A.
        • Coolen M.W.
        Regulatory roles for long ncRNA and mRNA.
        Cancers (Basel). 2013; 5: 462-490
        • Cesana M.
        • Cacchiarelli D.
        • Legnini I.
        • et al.
        A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA.
        Cell. 2011; 147: 358-369
        • Olivieri M.
        • Ferro M.
        • Terreri S.
        • et al.
        Long non-coding RNA containing ultraconserved genomic region 8 promotes bladder cancer tumorigenesis.
        Oncotarget. 2016; 7: 20636-20654
        • Hansen T.B.
        • Jensen T.I.
        • Clausen B.H.
        • et al.
        Natural RNA circles function as efficient microRNA sponges.
        Nature. 2013; 495: 384-388
        • Memczak S.
        • Jens M.
        • Elefsinioti A.
        • et al.
        Circular RNAs are a large class of animal RNAs with regulatory potency.
        Nature. 2013; 495: 333-338
        • Xie H.
        • Ren X.
        • Xin S.
        • et al.
        Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer.
        Oncotarget. 2016; 7: 26680-26691
        • Li P.
        • Chen S.
        • Chen H.
        • et al.
        Using circular RNA as a novel type of biomarker in the screening of gastric cancer.
        Clin Chim Acta. 2015; 444: 132-136
        • Bazzini A.A.
        • Johnstone T.G.
        • Christiano R.
        • et al.
        Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation.
        EMBO J. 2014; 33: 981-993
        • Anderson D.M.
        • Anderson K.M.
        • Chang C.L.
        • et al.
        A micropeptide encoded by a putative long noncoding RNA regulates muscle performance.
        Cell. 2015; 160: 595-606
        • Nelson B.R.
        • Makarewich C.A.
        • Anderson D.M.
        • et al.
        A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle.
        Science. 2016; 351: 271-275
        • Wang L.
        • Fu D.
        • Qiu Y.
        • Xing X.
        • Xu F.
        • Han C.
        • et al.
        Genome-wide screening and identification of long noncoding RNAs and their interaction with protein coding RNAs in bladder urothelial cell carcinoma.
        Cancer Lett. 2014; 349: 77-86
        • Melo S.A.
        • Luecke L.B.
        • Kahlert C.
        • et al.
        Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.
        Nature. 2015; 523: 177-182
        • Wang F.
        • Li X.
        • Xie X.
        • Zhao L.
        • Chen W.
        UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion.
        FEBS Lett. 2008; 582: 1919-1927
        • Pan J.
        • Li X.
        • Wu W.
        • et al.
        Long non-coding RNA UCA1 promotes cisplatin/gemcitabine resistance through CREB modulating miR-196a-5p in bladder cancer cells.
        Cancer Lett. 2016; 382: 64-76
        • Zhou H.
        • Yuen P.S.
        • Pisitkun T.
        • et al.
        Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery.
        Kidney Int. 2006; 69: 1471-1476
        • Zhang Z.
        • Hao H.
        • Zhang C.J.
        • Yang X.Y.
        • He Q.
        • Lin J.
        Zhonghua Yi Xue Za Zhi. 2012; 92: 384-387
        • 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. 1990; 10: 28-36
        • Elkin M.
        • Shevelev A.
        • Schulze E.
        • et al.
        The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma.
        FEBS Lett. 1995; 374: 57-61
        • Zhou Y.
        • Zhang X.
        • Klibanski A.
        MEG3 noncoding RNA: a tumor suppressor.
        J Mol Endocrinol. 2012; 48: R45-R53
        • Ariel I.
        • Lustig O.
        • Schneider T.
        • et al.
        The imprinted H19 gene as a tumor marker in bladder carcinoma.
        Urology. 1995; 45: 335-338
        • Ren S.
        • Liu Y.
        • Xu W.
        • et al.
        Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer.
        J Urol. 2013; 190: 2278-2287
        • Ji P.
        • Diederichs S.
        • Wang W.
        • et al.
        MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer.
        Oncogene. 2003; 22: 8031-8041
        • Han Y.
        • Liu Y.
        • Nie L.
        • Gui Y.
        • Cai Z.
        Inducing cell proliferation inhibition, apoptosis, and motility reduction by silencing long noncoding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 in urothelial carcinoma of the bladder.
        Urology. 2013; 81: 209.e1-209.e7
        • Ying L.
        • Chen Q.
        • Wang Y.
        • Zhou Z.
        • Huang Y.
        • Qiu F.
        Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition.
        Mol Biosyst. 2012; 8: 2289-2294
        • Iliev R.
        • Kleinova R.
        • Juracek J.
        • et al.
        Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer.
        Tumour Biol. 2016; 37: 13385-13390
        • Li J.
        • Zhuang C.
        • Liu Y.
        • et al.
        Synthetic tetracycline-controllable shRNA targeting long non-coding RNA HOXD-AS1 inhibits the progression of bladder cancer.
        J Exp Clin Cancer Res. 2016; 35: 99
        • Zhang S.
        • Zhong G.
        • He W.
        • Yu H.
        • Huang J.
        • Lin T.
        lncRNA up-regulated in nonmuscle invasive bladder cancer facilitates tumor growth and acts as a negative prognostic factor of recurrence.
        J Urol. 2016; 196: 1270-1278
        • Zhuang C.
        • Li J.
        • Liu Y.
        • et al.
        Tetracycline-inducible shRNA targeting long non-coding RNA PVT1 inhibits cell growth and induces apoptosis in bladder cancer cells.
        Oncotarget. 2015; 6: 41194-41203
        • Zhu Y.
        • Yu M.
        • Li Z.
        • et al.
        ncRAN, a newly identified long noncoding RNA, enhances human bladder tumor growth, invasion, and survival.
        Urology. 2011; 77: 510.e1-510.e5
        • Liu L.
        • Liu Y.
        • Zhuang C.
        • et al.
        Inducing cell growth arrest and apoptosis by silencing long non-coding RNA PCAT-1 in human bladder cancer.
        Tumour Biol. 2015; 36: 7685-7689
        • Li L.J.
        • Zhu J.L.
        • Bao W.S.
        • Chen D.K.
        • Huang W.W.
        • Weng Z.L.
        Long noncoding RNA GHET1 promotes the development of bladder cancer.
        Int J Clin Exp Pathol. 2014; 7: 7196-7205
        • Zhao X.L.
        • Zhao Z.H.
        • Xu W.C.
        • Hou J.Q.
        • Du X.Y.
        Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer.
        Int J Clin Exp Pathol. 2015; 8: 1954-1960
        • Ying L.
        • Huang Y.
        • Chen H.
        • et al.
        Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer.
        Mol Biosyst. 2013; 9: 407-411
        • Zhang X.
        • Zhou Y.
        • Mehta K.R.
        • et al.
        A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells.
        J Clin Endocrinol Metab. 2003; 88: 5119-5126
        • Zhang X.
        • Rice K.
        • Wang Y.
        • et al.
        Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions.
        Endocrinology. 2010; 151: 939-947
        • Duan W.
        • Du L.
        • Jiang X.
        • et al.
        Identification of a serum circulating lncRNA panel for the diagnosis and recurrence prediction of bladder cancer.
        Oncotarget. 2016; 7: 78850-78858
        • Cao Q.
        • Wang N.
        • Qi J.
        • Gu Z.
        • Shen H.
        Long noncoding RNAGAS5 acts as a tumor suppressor in bladder transitional cell carcinoma via regulation of chemokine (CC motif) ligand 1 expression.
        Mol Med Rep. 2016; 13: 27-34
        • Silva A.
        • Bullock M.
        • Calin G.
        The clinical relevance of long non-coding RNAs in cancer.
        Cancers (Basel). 2015; 7: 2169-2182
        • Rivas A.
        • Burzio V.
        • Landerer E.
        • et al.
        Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer.
        BMC Urol. 2012; 12: 37
        • Lorenzen J.M.
        • Schauerte C.
        • Kolling M.
        • et al.
        Long noncoding RNAs in urine are detectable and may enable early detection of acute T cell-mediated rejection of renal allografts.
        Clin Chem. 2015; 61: 1505-1514
        • Gonzales P.A.
        • Zhou H.
        • Pisitkun T.
        • et al.
        Isolation and purification of exosomes in urine.
        Methods Mol Biol. 2010; 641: 89-99
        • van Balkom B.W.
        • Pisitkun T.
        • Verhaar M.C.
        • Knepper M.A.
        Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases.
        Kidney Int. 2011; 80: 1138-1145
        • Welton J.L.
        • Khanna S.
        • Giles P.J.
        • et al.
        Proteomics analysis of bladder cancer exosomes.
        Mol Cell Proteomics. 2010; 9: 1324-1338
        • Miranda K.C.
        • Bond D.T.
        • McKee M.
        • et al.
        Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease.
        Kidney Int. 2010; 78: 191-199
        • Srivastava A.K.
        • Singh P.K.
        • Rath S.K.
        • Dalela D.
        • Goel M.M.
        • Bhatt M.L.
        Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder.
        Tumour Biol. 2014; 35: 11435-11442
        • Eissa S.
        • Matboli M.
        • Essawy N.O.
        • Shehta M.
        • Kotb Y.M.
        Rapid detection of urinary long non-coding RNA urothelial carcinoma associated one using a PCR-free nanoparticle-based assay.
        Biomarkers. 2015; 20: 212-217
        • Wang X.S.
        • Zhang Z.
        • Wang H.C.
        • et al.
        Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma.
        Clin Cancer Res. 2006; 12: 4851-4858
        • Moldovan L.
        • Batte K.
        • Wang Y.
        • Wisler J.
        • Piper M.
        Analyzing the circulating microRNAs in exosomes/extracellular vesicles from serum or plasma by qRT-PCR.
        Methods Mol Biol. 2013; 1024: 129-145
        • Gezer U.
        • Ozgur E.
        • Cetinkaya M.
        • Isin M.
        • Dalay N.
        Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes.
        Cell Biol Int. 2015; 38: 1076-1079
        • Martinez-Fernandez M.
        • Feber A.
        • Duenas M.
        • et al.
        Analysis of the polycomb-related lncRNAs HOTAIR and ANRIL in bladder cancer.
        Clin Epigenetics. 2015; 7: 109
        • van Rhijn B.W.
        • van der Poel H.G.
        • van der Kwast T.H.
        Urine markers for bladder cancer surveillance: a systematic review.
        Eur Urol. 2005; 47: 736-748
        • Calin G.A.
        • Liu C.G.
        • Ferracin M.
        • et al.
        Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.
        Cancer Cell. 2007; 12: 215-229
        • Prensner J.R.
        • Iyer M.K.
        • Balbin O.A.
        • et al.
        Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression.
        Nat Biotechnol. 2011; 29: 742-749
        • Hessels D.
        • Schalken J.A.
        The use of PCA3 in the diagnosis of prostate cancer.
        Nat Rev Urol. 2009; 6: 255-261
        • Vlaeminck-Guillem V.
        • Ruffion A.
        • Andre J.
        • Devonec M.
        • Paparel P.
        Urinary prostate cancer 3 test: toward the age of reason?.
        Urology. 2010; 75: 447-453
        • Roobol M.J.
        • Schroder F.H.
        • 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: 475-481
        • Bradley L.A.
        • Palomaki G.E.
        • Gutman S.
        • Samson D.
        • Aronson N.
        Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer.
        J Urol. 2013; 190: 389-398
        • Shariat S.F.
        • Karam J.A.
        • Lotan Y.
        • Karakiewizc P.I.
        Critical evaluation of urinary markers for bladder cancer detection and monitoring.
        Rev Urol. 2008; 10: 120-135