Long noncoding RNA in prostate, bladder, and kidney cancer.

CONTEXT Genomic regions without protein-coding potential give rise to millions of protein-noncoding RNA transcripts (noncoding RNA) that participate in virtually all cellular processes. Research over the last 10 yr has accumulated evidence that long noncoding RNAs (lncRNAs) are often altered in human urologic cancers. OBJECTIVE To review current progress in the biology and implication of lncRNAs associated with prostate, bladder, and kidney cancer. EVIDENCE ACQUISITION The PubMed database was searched for articles in the English language with combinations of the Medical Subject Headings terms long non coding RNA, long noncoding RNA, long untranslated RNA, cancer, neoplasms, prostate, bladder, and kidney. EVIDENCE SYNTHESIS We summarise existing knowledge on the systematics, biology, and function of lncRNAs, particularly these involved in prostate, kidney, and bladder cancer. We also discuss the possible utilisation of lncRNAs as novel biomarkers and potential therapeutic targets in urologic malignancies and portray the major challenges and future perspectives of ongoing lncRNA research. CONCLUSIONS LncRNAs are important regulators of gene expression interacting with the major pathways of cell growth, proliferation, differentiation, and survival. Alterations in the function of lncRNAs promote tumour formation, progression, and metastasis of prostate, bladder, and kidney cancer. LncRNAs can be used as noninvasive tumour markers in urologic malignancies. Increased knowledge of the molecular mechanisms by which lncRNAs perform their function in the normal and malignant cell will lead to a better understanding of tumour biology and could provide novel therapeutic targets for the treatment of urologic cancers. PATIENT SUMMARY In this paper we reviewed current knowledge of long noncoding RNAs (lncRNAs) for the detection and treatment of urologic cancers. We conclude that lncRNAs can be used as novel biomarkers in prostate, kidney, or bladder cancer. LncRNAs hold promise as future therapeutic targets, but more research is needed to gain a better understanding of their biologic function.

[1]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[2]  Sebastian D. Mackowiak,et al.  Circular RNAs are a large class of animal RNAs with regulatory potency , 2013, Nature.

[3]  Jianfeng Xu,et al.  Human polymorphisms at long non-coding RNAs (lncRNAs) and association with prostate cancer risk. , 2011, Carcinogenesis.

[4]  Carolyn J. Brown,et al.  A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome , 1991, Nature.

[5]  A. Hochberg,et al.  Possible physiological role of H19 RNA , 2002, Molecular carcinogenesis.

[6]  Thomas D. Schmittgen,et al.  Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. , 2007, Cancer cell.

[7]  I. Rigoutsos,et al.  The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis , 2012, Cellular and Molecular Life Sciences.

[8]  Meng Li,et al.  Rapid Identification of UCA1 as a Very Sensitive and Specific Unique Marker for Human Bladder Carcinoma , 2006, Clinical Cancer Research.

[9]  H. Okabe,et al.  Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. , 2006, Human molecular genetics.

[10]  Chen Yang,et al.  Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells. , 2012, Gene.

[11]  Michael Thomas,et al.  MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer , 2003, Oncogene.

[12]  Howard Y. Chang,et al.  Extensive and coordinated transcription of noncoding RNAs within cell cycle promoters , 2011, Nature Genetics.

[13]  Jianxin Qiu,et al.  Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expression , 2013, The FEBS journal.

[14]  A. Schetter,et al.  Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer , 2013, Molecular Cancer.

[15]  Zhiming Cai,et al.  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. , 2013, Urology.

[16]  J. Uney,et al.  The Application of Ribozymes and DNAzymes in Muscle and Brain , 2010, Molecules.

[17]  M. Ladanyi,et al.  Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Yin,et al.  Association between lncrna PCGEM1 polymorphisms and prostate cancer risk , 2013, Prostate Cancer and Prostatic Diseases.

[19]  J. Igietseme,et al.  Differential effects of cholesterol and phytosterols on cell proliferation, apoptosis and expression of a prostate specific gene in prostate cancer cell lines. , 2009, Cancer detection and prevention.

[20]  Zhenhua Li,et al.  ncRAN, a newly identified long noncoding RNA, enhances human bladder tumor growth, invasion, and survival. , 2011, Urology.

[21]  M. Rosenfeld,et al.  LncRNA-Dependent Mechanisms of Androgen Receptor-regulated Gene Activation Programs , 2013, Nature.

[22]  N. Zaffaroni,et al.  Characterization of novel antisense HIF-1α transcripts in human cancers , 2011, Cell cycle.

[23]  I. Gut,et al.  DNA sequencing - spanning the generations. , 2012, New biotechnology.

[24]  Saskia D. Hiltemann,et al.  Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line , 2013, Human Genetics.

[25]  K. Morris,et al.  A pseudogene long noncoding RNA network regulates PTEN transcription and translation in human cells , 2013, Nature Structural &Molecular Biology.

[26]  Wei Gao,et al.  Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[27]  Martina Paulsen,et al.  Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region. , 2002, Human molecular genetics.

[28]  G. Ifere,et al.  Prostate cancer gene expression marker 1 (PCGEM1): a patented prostate- specific non-coding gene and regulator of prostate cancer progression. , 2009, Recent patents on DNA & gene sequences.

[29]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[30]  Sunjong Kwon.  Single-molecule fluorescence in situ hybridization: Quantitative imaging of single RNA molecules , 2013, BMB reports.

[31]  Yiran Huang,et al.  Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. , 2012, Molecular bioSystems.

[32]  A. Feinberg,et al.  Erratum: LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids (Human Molecular Genetics (1999) 8 (1209-1217)) , 1999 .

[33]  A. Hochberg,et al.  The expression of the imprinted H19 and IGF‐2 genes in human bladder carcinoma , 1995, FEBS letters.

[34]  C. Thrash-Bingham,et al.  aHIF: a natural antisense transcript overexpressed in human renal cancer and during hypoxia. , 1999, Journal of the National Cancer Institute.

[35]  C. Glass,et al.  Reprogramming Transcription via Distinct Classes of Enhancers Functionally Defined by eRNA , 2011, Nature.

[36]  Mathew W. Wright,et al.  Naming 'junk': Human non-protein coding RNA (ncRNA) gene nomenclature , 2011, Human Genomics.

[37]  D. Bostwick,et al.  Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases. , 2012, The Journal of urology.

[38]  G. B. Petersen,et al.  Methylation Sequencing Analysis Refines the Region ofH19 Epimutation in Wilms Tumor* , 1999, The Journal of Biological Chemistry.

[39]  M. Shen.  Chromoplexy: a new category of complex rearrangements in the cancer genome. , 2013, Cancer cell.

[40]  J. Mattick,et al.  Structure and function of long noncoding RNAs in epigenetic regulation , 2013, Nature Structural &Molecular Biology.

[41]  O. Ogawa,et al.  XISTunmethylated DNA fragments in male-derived plasma as a tumour marker for testicular cancer , 2004, The Lancet.

[42]  Wolfgang A. Schulz,et al.  Hypomethylation of the XIST gene promoter in prostate cancer. , 2005, Oncology research.

[43]  Martin Renqiang Min,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[44]  C. Croce,et al.  microRNA involvement in human cancer. , 2012, Carcinogenesis.

[45]  E. Dees,et al.  The product of the H19 gene may function as an RNA , 1990, Molecular and cellular biology.

[46]  Pieter C. Dorrestein,et al.  ncRNA- and Pc2 Methylation-Dependent Gene Relocation between Nuclear Structures Mediates Gene Activation Programs , 2011, Cell.

[47]  A. Feinberg,et al.  LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids. , 1999, Human molecular genetics.

[48]  Chuanliang Xu,et al.  The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. , 2013, Urologic oncology.

[49]  A. Hochberg,et al.  The imprinted H19 gene is a marker of early recurrence in human bladder carcinoma , 2000, Molecular pathology : MP.

[50]  Y Kopelman,et al.  Phase 1/2a, dose-escalation, safety, pharmacokinetic and preliminary efficacy study of intratumoral administration of BC-819 in patients with unresectable pancreatic cancer , 2012, Cancer Gene Therapy.

[51]  R. Weindruch,et al.  Aging and cancer-related loss of insulin-like growth factor 2 imprinting in the mouse and human prostate. , 2008, Cancer research.

[52]  J. Kjems,et al.  Natural RNA circles function as efficient microRNA sponges , 2013, Nature.

[53]  Wei Wang,et al.  Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. , 2013, Cancer letters.

[54]  Eric S. Lander,et al.  The genomic complexity of primary human prostate cancer , 2010, Nature.

[55]  Beth Israel,et al.  Decision letter: Replication Study: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology , 2010 .

[56]  J. Svaren,et al.  A Loss of Insulin-like Growth Factor-2 Imprinting Is Modulated by CCCTC-binding Factor Down-regulation at Senescence in Human Epithelial Cells* , 2004, Journal of Biological Chemistry.

[57]  E. van den Berg,et al.  Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution. , 2003, Human molecular genetics.

[58]  M. Loda,et al.  Identification of the miR-106b~25 MicroRNA Cluster as a Proto-Oncogenic PTEN-Targeting Intron That Cooperates with Its Host Gene MCM7 in Transformation , 2010, Science Signaling.

[59]  Peter Goodfellow,et al.  Circular transcripts of the testis-determining gene Sry in adult mouse testis , 1993, Cell.

[60]  R. Shiekhattar,et al.  Activating RNAs associate with Mediator to enhance chromatin architecture and transcription , 2013, Nature.

[61]  G. Chrousos,et al.  Noncoding RNA Gas5 Is a Growth Arrest– and Starvation-Associated Repressor of the Glucocorticoid Receptor , 2010, Science Signaling.

[62]  D. McDonnell,et al.  A negative coregulator for the human ER. , 2002, Molecular endocrinology.

[63]  Suman Lee,et al.  Quantification of CpG methylation at the 5′‐region of XIST by pyrosequencing from human serum , 2007, Electrophoresis.

[64]  Karissa Y. Sanbonmatsu,et al.  Structural architecture of the human long non-coding RNA, steroid receptor RNA activator , 2012, Nucleic acids research.

[65]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[66]  H. Aburatani,et al.  Androgen‐responsive long noncoding RNA CTBP1‐AS promotes prostate cancer , 2013, The EMBO journal.

[67]  John T. Wei,et al.  Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression , 2011, Nature Biotechnology.

[68]  Bruce M. Wentworth,et al.  Targeting nuclear RNA for in vivo correction of myotonic dystrophy , 2012, Nature.

[69]  A. Hochberg,et al.  The H19 Non-Coding RNA Is Essential for Human Tumor Growth , 2007, PloS one.

[70]  T. Visakorpi,et al.  Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer , 2012, Oncogene.

[71]  J. Komorowski,et al.  Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. , 2008, Molecular cell.

[72]  Chen Yang,et al.  Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer. , 2012, International journal of oncology.

[73]  Toshiro K. Ohsumi,et al.  Genome-wide identification of polycomb-associated RNAs by RIP-seq. , 2010, Molecular cell.

[74]  W. Isaacs,et al.  DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. , 1999, Cancer research.

[75]  Jing Zhao,et al.  Activation of p53 by MEG3 Non-coding RNA* , 2007, Journal of Biological Chemistry.

[76]  Wei Zhang,et al.  Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients , 2004, Oncogene.

[77]  Qizhi Yao,et al.  Expression and Function of a Large Non-coding RNA Gene XIST in Human Cancer , 2011, World Journal of Surgery.

[78]  M. Augustus,et al.  PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[79]  Abraham Hochberg,et al.  Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF2-P4 regulatory sequences , 2010, Journal of Translational Medicine.

[80]  E. Martens-Uzunova,et al.  Beyond microRNA--novel RNAs derived from small non-coding RNA and their implication in cancer. , 2013, Cancer letters.

[81]  Ferdinando Di Cunto,et al.  Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs , 2011, Cell.

[82]  M. Karin,et al.  A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas , 2007, Oncogene.

[83]  D. Takai,et al.  Large scale mapping of methylcytosines in CTCF-binding sites in the human H19 promoter and aberrant hypomethylation in human bladder cancer. , 2001, Human molecular genetics.

[84]  Xu Li,et al.  UCA1, a non‐protein‐coding RNA up‐regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion , 2008, FEBS letters.

[85]  L. Kiemeney,et al.  Polymorphisms in the H19 gene and the risk of bladder cancer. , 2008, European urology.

[86]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[87]  V. Iotsova,et al.  The H19 TATA-less promoter is efficiently repressed by wild-type tumor suppressor gene product p53 , 1998, Oncogene.

[88]  Igor Jurisica,et al.  The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. , 2006, Cancer research.

[89]  C. Kanduri,et al.  The KCNQ1OT1 imprinting control region and non-coding RNA: new properties derived from the study of Beckwith–Wiedemann syndrome and Silver–Russell syndrome cases , 2011, Human molecular genetics.

[90]  Howard Y. Chang,et al.  A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression , 2011, Nature.

[91]  Yiran Huang,et al.  Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. , 2013, Molecular bioSystems.

[92]  Nadav S. Bar,et al.  Landscape of transcription in human cells , 2012, Nature.

[93]  N. Tran,et al.  Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1. , 2006, DNA and cell biology.

[94]  Yuehua Wu,et al.  Long noncoding RNAs with snoRNA ends. , 2012, Molecular cell.

[95]  Yunli Zhou,et al.  MEG3 noncoding RNA: a tumor suppressor. , 2012, Journal of molecular endocrinology.

[96]  P. Pandolfi,et al.  A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? , 2011, Cell.

[97]  Zhiming Cai,et al.  Long intergenic non‐coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder , 2013, Journal of surgical oncology.

[98]  Yusuke Nakamura,et al.  Association of a novel long non‐coding RNA in 8q24 with prostate cancer susceptibility , 2011, Cancer science.

[99]  A. Oudenaarden,et al.  Validating transcripts with probes and imaging technology , 2011, Nature Methods.

[100]  M. Kyba,et al.  The H19 lincRNA is a developmental reservoir of miR-675 which suppresses growth and Igf1r , 2012, Nature Cell Biology.