LncRNA-mediated regulation of cell signaling in cancer

To date, a large number of long non-coding RNAs (lncRNAs) have been recently discovered through functional genomics studies. Importantly, lncRNAs have been shown, in many cases, to function as master regulators for gene expression and thus, they can play a critical role in various biological functions and disease processes including cancer. Although the lncRNA-mediated gene expression involves various mechanisms, such as regulation of transcription, translation, protein modification, and the formation of RNA–protein or protein–protein complexes, in this review, we discuss the latest developments primarily in important cell signaling pathways regulated by lncRNAs in cancer.

[1]  Reuven Agami,et al.  Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA , 2015, Nature Communications.

[2]  T. Jiang,et al.  Long non-coding RNA BC087858 induces non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT in non-small-cell lung cancer , 2016, Oncotarget.

[3]  H. Yao,et al.  A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. , 2015, Cancer cell.

[4]  S. Tilghman.  Parental imprinting in the mouse. , 1991, Harvey lectures.

[5]  R. Grover,et al.  Polypyrimidine tract binding protein regulates IRES-mediated translation of p53 isoforms , 2008, Cell cycle.

[6]  D. Bartel,et al.  lincRNAs: Genomics, Evolution, and Mechanisms , 2013, Cell.

[7]  C. Ponting,et al.  Intergenic lncRNAs and the evolution of gene expression. , 2014, Current opinion in genetics & development.

[8]  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.

[9]  Jing Chen,et al.  LincRNA-Cox2 Promotes Late Inflammatory Gene Transcription in Macrophages through Modulating SWI/SNF-Mediated Chromatin Remodeling , 2016, The Journal of Immunology.

[10]  Ji Luo,et al.  The phosphoinositide 3-kinase regulatory subunit p85alpha can exert tumor suppressor properties through negative regulation of growth factor signaling. , 2010, Cancer research.

[11]  Kotb Abdelmohsen,et al.  LincRNA-p21 suppresses target mRNA translation. , 2012, Molecular cell.

[12]  Y. Totoki,et al.  Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment , 2016, Nature Communications.

[13]  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.

[14]  Carolyn J. Brown,et al.  The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus , 1992, Cell.

[15]  Carolyn J. Brown,et al.  The functional role of long non-coding RNA in human carcinomas , 2011, Molecular Cancer.

[16]  M. Esteller.  Non-coding RNAs in human disease , 2011, Nature Reviews Genetics.

[17]  Fangting Wu,et al.  LncRNA AK023948 is a positive regulator of AKT , 2017, Nature Communications.

[18]  A. Masotti,et al.  Long Non-Coding RNAs and p53 Regulation , 2012, International journal of molecular sciences.

[19]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[20]  Howard Y. Chang,et al.  Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes , 2010, Science.

[21]  B. Emerson,et al.  p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-κB complexes , 2014, eLife.

[22]  Y. Wang,et al.  Mammalian ncRNA-disease repository: a global view of ncRNA-mediated disease network , 2013, Cell Death and Disease.

[23]  K. Shirahige,et al.  MYU, a Target lncRNA for Wnt/c-Myc Signaling, Mediates Induction of CDK6 to Promote Cell Cycle Progression. , 2016, Cell reports.

[24]  T. Gingeras,et al.  Genome-wide transcription and the implications for genomic organization , 2007, Nature Reviews Genetics.

[25]  Charles S Bond,et al.  The ins and outs of lncRNA structure: How, why and what comes next? , 2016, Biochimica et biophysica acta.

[26]  Piero Carninci,et al.  Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat , 2012, Nature.

[27]  Y. Mo,et al.  Negative regulation of lncRNA GAS5 by miR-21 , 2013, Cell Death and Differentiation.

[28]  R. McCarthy,et al.  LncPRESS1 Is a p53-Regulated LncRNA that Safeguards Pluripotency by Disrupting SIRT6-Mediated De-acetylation of Histone H3K56. , 2016, Molecular cell.

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

[30]  D. Song,et al.  The long noncoding RNA MALAT1 regulates the lipopolysaccharide‐induced inflammatory response through its interaction with NF‐κB , 2016, FEBS letters.

[31]  S. Lawler,et al.  MicroRNAs in cancer: biomarkers, functions and therapy. , 2014, Trends in molecular medicine.

[32]  Howard Y. Chang,et al.  Genome regulation by long noncoding RNAs. , 2012, Annual review of biochemistry.

[33]  Leng Han,et al.  The LINK-A lncRNA interacts with PI(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors , 2017, Nature Cell Biology.

[34]  Fangting Wu,et al.  Regulation of androgen receptor splice variant AR3 by PCGEM1 , 2016, Oncotarget.

[35]  V. Meller,et al.  Modulation of Chromatin by Noncoding RNA. , 2015, Annual review of genetics.

[36]  A. Veronese,et al.  Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers , 2016, Gut.

[37]  M. Bartolomei,et al.  Parental imprinting of the mouse H19 gene , 1991, Nature.

[38]  J. Rinn,et al.  A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response , 2010, Cell.

[39]  Y. Mo,et al.  The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage , 2012, Cell Research.

[40]  Xuhui Zhou,et al.  MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway , 2015, Tumor Biology.

[41]  F. Setién,et al.  Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer , 2016, Proceedings of the National Academy of Sciences.

[42]  Howard Y. Chang,et al.  An inducible long noncoding RNA amplifies DNA damage signaling , 2016, Nature Genetics.

[43]  J. Abbruzzese,et al.  Regulation of interleukin-8 expression by cellular pH in human pancreatic adenocarcinoma cells. , 2000, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[44]  Aristotelis Tsirigos,et al.  Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs in Acute Leukemia , 2014, Cell.

[45]  Y. Mo,et al.  Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1) , 2014, Cell Death and Disease.

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

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

[48]  Hongwei Wu,et al.  LncRNA-HOTAIR promotes TNF-α production in cardiomyocytes of LPS-induced sepsis mice by activating NF-κB pathway. , 2016, Biochemical and biophysical research communications.

[49]  Simon W. Jones,et al.  Long Intergenic Noncoding RNAs Mediate the Human Chondrocyte Inflammatory Response and Are Differentially Expressed in Osteoarthritis Cartilage , 2016, Arthritis & rheumatology.

[50]  A. Fatica,et al.  Long non-coding RNAs: new players in cell differentiation and development , 2013, Nature Reviews Genetics.

[51]  Da-Qing Yang,et al.  p53 translational control: a new facet of p53 regulation and its implication for tumorigenesis and cancer therapeutics. , 2007, Gene.

[52]  B. Aggarwal,et al.  Nuclear factor-kappaB: the enemy within. , 2004, Cancer cell.

[53]  Y. Mo,et al.  MALAT1-mediated tumorigenesis. , 2017, Frontiers in bioscience.

[54]  Y. Mo,et al.  Linc-RoR promotes c-Myc expression through hnRNP I and AUF1 , 2015, Nucleic acids research.

[55]  Howard Y. Chang,et al.  Molecular mechanisms of long noncoding RNAs. , 2011, Molecular cell.

[56]  Tao Lu,et al.  NF-κB: Regulation by Methylation. , 2015, Cancer research.

[57]  Rajvir Dahiya,et al.  Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205. , 2015, Cancer research.

[58]  B. Frey,et al.  Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing , 2008, Nature Genetics.

[59]  C. Demaria,et al.  AUF1 Binding Affinity to A+U-rich Elements Correlates with Rapid mRNA Degradation (*) , 1996, The Journal of Biological Chemistry.

[60]  J. Rinn,et al.  Discovery and annotation of long noncoding RNAs , 2015, Nature Structural &Molecular Biology.

[61]  J. Manley,et al.  hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing. , 2007, Human molecular genetics.

[62]  Y. Mo,et al.  Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis , 2016, Cell Death and Disease.

[63]  John M. Shelton,et al.  A Micropeptide Encoded by a Putative Long Noncoding RNA Regulates Muscle Performance , 2015, Cell.

[64]  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.

[65]  Yue Wang,et al.  Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. , 2013, Developmental cell.

[66]  Leng Han,et al.  The LINK-A lncRNA Activates Normoxic HIF1α Signaling in Triple-negative Breast Cancer , 2016, Nature Cell Biology.

[67]  S. Batalov,et al.  Antisense Transcription in the Mammalian Transcriptome , 2005, Science.

[68]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[69]  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.

[70]  D. Matei,et al.  NF-κB-HOTAIR axis links DNA damage response, chemoresistance and cellular senescence in ovarian cancer , 2016, Oncogene.

[71]  D. Largaespada,et al.  PVT1 dependence in cancer with MYC copy-number increase , 2014, Nature.

[72]  J. Wilusz.  Long noncoding RNAs: Re-writing dogmas of RNA processing and stability. , 2016, Biochimica et biophysica acta.

[73]  Hong Li,et al.  LncRNA FER1L4 suppresses cancer cell proliferation and cycle by regulating PTEN expression in endometrial carcinoma. , 2016, Biochemical and biophysical research communications.

[74]  Julian König,et al.  Direct Competition between hnRNP C and U2AF65 Protects the Transcriptome from the Exonization of Alu Elements , 2013, Cell.

[75]  Y. Mo,et al.  Role of the lncRNA-p53 regulatory network in cancer. , 2014, Journal of molecular cell biology.

[76]  B. Blencowe,et al.  The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. , 2010, Molecular cell.

[77]  F. Liu,et al.  Downregulation of long noncoding RNA MALAT1 induces epithelial-to-mesenchymal transition via the PI3K-AKT pathway in breast cancer. , 2015, International journal of clinical and experimental pathology.

[78]  I. Fidler,et al.  Acidic pH-induced elevation in interleukin 8 expression by human ovarian carcinoma cells. , 2000, Cancer research.

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

[80]  Stephen C. Cannon,et al.  A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle , 2016, Science.

[81]  Jun Lu,et al.  The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and metastasis of breast cancer , 2016, Cell Death and Differentiation.

[82]  Fangting Wu,et al.  LncRNA loc285194 is a p53-regulated tumor suppressor , 2013, Nucleic acids research.

[83]  Hailong Wu,et al.  p53 represses c-Myc through induction of the tumor suppressor miR-145 , 2009, Proceedings of the National Academy of Sciences.

[84]  F. Bianchini,et al.  Acidic pH via NF-κB favours VEGF-C expression in human melanoma cells , 2013, Clinical & Experimental Metastasis.

[85]  R. Elkon,et al.  eRNAs are required for p53-dependent enhancer activity and gene transcription. , 2013, Molecular cell.

[86]  Jean J. Zhao,et al.  PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting , 2014, Nature Reviews Cancer.

[87]  Yaping Wang,et al.  LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia , 2015, Scientific Reports.