RNA-Binding Proteins in Cancer: Old Players and New Actors.

RNA-binding proteins (RBPs) are key players in post-transcriptional events. The combination of versatility of their RNA-binding domains with structural flexibility enables RBPs to control the metabolism of a large array of transcripts. Perturbations in RBP-RNA networks activity have been causally associated with cancer development, but the rational framework describing these contributions remains fragmented. We review here the evidence that RBPs modulate multiple cancer traits, emphasize their functional diversity, and assess future trends in the study of RBPs in cancer.

[1]  Ivo L. Hofacker,et al.  AREsite: a database for the comprehensive investigation of AU-rich elements , 2010, Nucleic Acids Res..

[2]  A. Krainer,et al.  The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism , 2010, Proceedings of the National Academy of Sciences.

[3]  F. Real,et al.  Key contribution of CPEB4-mediated translational control to cancer progression , 2011, Nature Medicine.

[4]  Y. Ionov,et al.  RNA-binding motif protein 35A is a novel tumor suppressor for colorectal cancer , 2009, Cell cycle.

[5]  S. Janga,et al.  The human RBPome: from genes and proteins to human disease. , 2015, Journal of proteomics.

[6]  Shelly C. Lu,et al.  HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. , 2010, Gastroenterology.

[7]  R. Schneider,et al.  Physiological networks and disease functions of RNA‐binding protein AUF1 , 2014, Wiley interdisciplinary reviews. RNA.

[8]  Libing Song,et al.  Sam68 up‐regulation correlates with, and its down‐regulation inhibits, proliferation and tumourigenicity of breast cancer cells , 2010, The Journal of pathology.

[9]  M. Gorospe,et al.  Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs , 2004, The EMBO journal.

[10]  Michael G. Kharas,et al.  Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program. , 2015, The Journal of clinical investigation.

[11]  Nicolò Riggi,et al.  Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. , 2012, Genes & development.

[12]  S. Endres,et al.  RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8+ T cells , 2014, Cell Death and Differentiation.

[13]  Stephen T. C. Wong,et al.  Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells , 2013, PloS one.

[14]  Felice-Alessio Bava,et al.  Sequential Functions of CPEB1 and CPEB4 Regulate Pathologic Expression of Vascular Endothelial Growth Factor and Angiogenesis in Chronic Liver Disease. , 2016, Gastroenterology.

[15]  Kotb Abdelmohsen,et al.  Posttranscriptional regulation of cancer traits by HuR , 2010, Wiley interdisciplinary reviews. RNA.

[16]  Qiang Zhou,et al.  LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis , 2014, eLife.

[17]  J. Valcárcel,et al.  Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks , 2016, Genome research.

[18]  Scott B. Dewell,et al.  Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP , 2010, Cell.

[19]  R. Cardiff,et al.  Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors , 2014, Proceedings of the National Academy of Sciences.

[20]  Johanne Toutant,et al.  Small interfering RNA-mediated reduction in heterogeneous nuclear ribonucleoparticule A1/A2 proteins induces apoptosis in human cancer cells but not in normal mortal cell lines. , 2003, Cancer research.

[21]  E. Eyras,et al.  Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers , 2016, Nature Communications.

[22]  R. Gregory,et al.  MicroRNA biogenesis pathways in cancer , 2015, Nature Reviews Cancer.

[23]  Eurie L. Hong,et al.  Resources for the comprehensive discovery of functional RNA elements , 2015, bioRxiv.

[24]  P. Kafasla,et al.  Post-transcriptional coordination of immunological responses by RNA-binding proteins , 2014, Nature Immunology.

[25]  A. Krainer,et al.  THE SPLICING FACTOR SRSF1 REGULATES APOPTOSIS AND PROLIFERATION TO PROMOTE MAMMARY EPITHELIAL CELL TRANSFORMATION , 2011, Nature Structural &Molecular Biology.

[26]  Hiroshi Tanaka,et al.  Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell , 2012, Nature Communications.

[27]  Jernej Ule,et al.  CLIP: a method for identifying protein-RNA interaction sites in living cells. , 2005, Methods.

[28]  A. Caflisch,et al.  A Small-Molecule Inhibitor of Lin28. , 2016, ACS chemical biology.

[29]  Mark J. Bowser,et al.  IMP-1 displays cross-talk with K-Ras and modulates colon cancer cell survival through the novel proapoptotic protein CYFIP2. , 2011, Cancer research.

[30]  Kotb Abdelmohsen,et al.  Posttranscriptional Orchestration of an Anti-Apoptotic Program by HuR , 2007, Cell cycle.

[31]  Sadaf Ghaem-Maghami,et al.  The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer , 2015, Nucleic acids research.

[32]  C. Mayr,et al.  Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells , 2009, Cell.

[33]  N. Carter,et al.  Genomic Profiling Identifies Discrete Deletions Associated with Translocations in Glioblastoma Multiforme , 2006, Cell cycle.

[34]  A. Krainer,et al.  Splicing-factor oncoprotein SRSF1 stabilizes p53 via RPL5 and induces cellular senescence. , 2013, Molecular cell.

[35]  Caiying Guo,et al.  Essential role of the RNA-binding protein HuR in progenitor cell survival in mice. , 2009, The Journal of clinical investigation.

[36]  Chonghui Cheng,et al.  Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing , 2014, Genes & development.

[37]  P. Pandolfi,et al.  The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis , 2004, Nature Medicine.

[38]  Jeroen Krijgsveld,et al.  The RNA-binding proteomes from yeast to man harbour conserved enigmRBPs , 2015, Nature Communications.

[39]  Xintao Wei,et al.  Resources for the comprehensive discovery of functional RNA elements , 2015, bioRxiv.

[40]  R. Korneluk,et al.  Functional Characterization of the X-Linked Inhibitor of Apoptosis (XIAP) Internal Ribosome Entry Site Element: Role of La Autoantigen in XIAP Translation , 2000, Molecular and Cellular Biology.

[41]  A. Hsieh,et al.  Targeting Eukaryotic Translation Initiation Factor 4E (eIF4E) in Cancer , 2010, Clinical Cancer Research.

[42]  K. Miyazono,et al.  RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma , 2016, Oncogene.

[43]  E. Laing,et al.  Conserved mRNA-binding proteomes in eukaryotic organisms , 2015, Nature Structural &Molecular Biology.

[44]  J. M. Izquierdo,et al.  T-cell intracellular antigens function as tumor suppressor genes , 2015, Cell Death and Disease.

[45]  M. Plateroti,et al.  CDX2 regulation by the RNA-binding protein MEX3A: impact on intestinal differentiation and stemness , 2013, Nucleic acids research.

[46]  J. Valcárcel,et al.  RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation. , 2013, Molecular cell.

[47]  M. Petz,et al.  La enhances IRES-mediated translation of laminin B1 during malignant epithelial to mesenchymal transition , 2011, Nucleic acids research.

[48]  M. McArthur,et al.  hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies. , 2015, Cancer cell.

[49]  Takahiro Ito,et al.  Regulation of myeloid leukemia by the cell fate determinant Musashi , 2010, Nature.

[50]  S. Srikantan,et al.  RNA-binding protein AUF1 represses Dicer expression , 2012, Nucleic acids research.

[51]  Myriam Gorospe,et al.  HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation , 2000, The EMBO journal.

[52]  T. Hyslop,et al.  Alternative splicing of the cyclin D1 proto-oncogene is regulated by the RNA-binding protein Sam68. , 2010, Cancer research.

[53]  Simone Brabletz,et al.  A self‐enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells , 2015, International journal of cancer.

[54]  F. Ferrari,et al.  A MicroRNA Targeting Dicer for Metastasis Control , 2010, Cell.

[55]  G. Gonye,et al.  Delivery of Therapeutics Targeting the mRNA-Binding Protein HuR Using 3DNA Nanocarriers Suppresses Ovarian Tumor Growth. , 2016, Cancer research.

[56]  J. Condeelis,et al.  Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1 , 2005, Nature.

[57]  Kai-Wei Chang,et al.  RNA-binding proteins in human genetic disease. , 2008, Trends in genetics : TIG.

[58]  M. Gorospe,et al.  Posttranscriptional derepression of GADD45alpha by genotoxic stress. , 2006, Molecular cell.

[59]  J. M. Izquierdo,et al.  Knockdown of T-cell intracellular antigens triggers cell proliferation, invasion and tumour growth. , 2011, The Biochemical journal.

[60]  Ilan Davis,et al.  The new (dis)order in RNA regulation , 2016, Cell Communication and Signaling.

[61]  A. Rezza,et al.  The overexpression of the putative gut stem cell marker Musashi-1 induces tumorigenesis through Wnt and Notch activation , 2010, Journal of Cell Science.

[62]  Pedro G. Ferreira,et al.  CPEB1 coordinates alternative 3′-UTR formation with translational regulation , 2013, Nature.

[63]  J. Mulshine,et al.  hnRNP A2/B1 modulates epithelial-mesenchymal transition in lung cancer cell lines. , 2010, Cancer research.

[64]  Tyson A. Clark,et al.  HITS-CLIP yields genome-wide insights into brain alternative RNA processing , 2008, Nature.

[65]  Davide Ruggero,et al.  New frontiers in translational control of the cancer genome , 2016, Nature Reviews Cancer.

[66]  J. Graber,et al.  Global changes in processing of mRNA 3' untranslated regions characterize clinically distinct cancer subtypes. , 2009, Cancer research.

[67]  Omar Abdel-Wahab,et al.  Therapeutic targeting of splicing in cancer , 2016, Nature Medicine.

[68]  J. Ule,et al.  iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution , 2010, Nature Structural &Molecular Biology.

[69]  Guanghui Wang,et al.  miR-574-5p negatively regulates Qki6/7 to impact β-catenin/Wnt signalling and the development of colorectal cancer , 2012, Gut.

[70]  F. Dilworth,et al.  Nuclear matrix-associated protein SMAR1 regulates alternative splicing via HDAC6-mediated deacetylation of Sam68 , 2015, Proceedings of the National Academy of Sciences.

[71]  Yi Xing,et al.  An ESRP‐regulated splicing programme is abrogated during the epithelial–mesenchymal transition , 2010, The EMBO journal.

[72]  Zefeng Wang,et al.  A splicing isoform of TEAD4 attenuates the Hippo–YAP signalling to inhibit tumour proliferation , 2016, Nature Communications.

[73]  L. Nabors,et al.  HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3' untranslated regions of cytokine and angiogenic factor mRNAs. , 2001, Cancer research.

[74]  N. Jahchan,et al.  A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-dependent transcriptional elongation and tumorigenesis. , 2008, Molecular cell.

[75]  Shane T. Jensen,et al.  The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins. , 2015, Cell reports.

[76]  Luc Girard,et al.  ZEB1 drives epithelial-to-mesenchymal transition in lung cancer. , 2016, The Journal of clinical investigation.

[77]  Eugene V Koonin,et al.  Comparative genomics and evolution of proteins involved in RNA metabolism. , 2002, Nucleic acids research.

[78]  R. Parker,et al.  Principles and properties of eukaryotic mRNPs. , 2014, Molecular cell.

[79]  L. Schwartz,et al.  The novel lupus antigen related protein acheron enhances the development of human breast cancer , 2012, International journal of cancer.

[80]  W. Gu,et al.  Blocking β-catenin binding to the ZBP1 promoter represses ZBP1 expression, leading to increased proliferation and migration of metastatic breast-cancer cells , 2009, Journal of Cell Science.

[81]  A. Chinnaiyan,et al.  Long noncoding RNAs in cancer: from function to translation. , 2015, Trends in cancer.

[82]  T. Tokuyasu,et al.  Differential Requirements for eIF4E Dose in Normal Development and Cancer , 2015, Cell.

[83]  M. Caligiuri,et al.  BCR/ABL activates mdm2 mRNA translation via the La antigen. , 2003, Cancer cell.

[84]  Monika Heiner,et al.  The RNA-Binding Protein QKI Suppresses Cancer-Associated Aberrant Splicing , 2014, PLoS genetics.

[85]  S. Chi,et al.  NF-kappaB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis. , 2008, Gastroenterology.

[86]  I. Babic,et al.  The RNA binding protein Sam68 is acetylated in tumor cell lines, and its acetylation correlates with enhanced RNA binding activity , 2004, Oncogene.

[87]  J. Richter,et al.  CPEB mediated ZO-1 mRNA Localization is Required for Epithelial Tight Junction Assembly and Cell Polarity , 2012, Nature Communications.

[88]  Gene W. Yeo,et al.  Robust transcriptome-wide discovery of RNA binding protein binding sites with enhanced CLIP (eCLIP) , 2016, Nature Methods.

[89]  A E Willis,et al.  LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression , 2014, Oncogene.

[90]  Guodong Yang,et al.  RNA-binding protein quaking, a critical regulator of colon epithelial differentiation and a suppressor of colon cancer. , 2010, Gastroenterology.

[91]  Michael Q. Zhang,et al.  Design and bioinformatics analysis of genome-wide CLIP experiments , 2015, Nucleic acids research.

[92]  D. Dixon,et al.  Identification and validation of novel small molecule disruptors of HuR-mRNA interaction. , 2015, ACS chemical biology.

[93]  Panagiotis K. Papasaikas,et al.  UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis. , 2016, Cancer cell.

[94]  S. Itzkovitz,et al.  A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells , 2015, Nature Communications.

[95]  A. Corbett,et al.  Post-transcriptional Regulation of Programmed Cell Death 4 (PDCD4) mRNA by the RNA-binding Proteins Human Antigen R (HuR) and T-cell Intracellular Antigen 1 (TIA1)* , 2014, The Journal of Biological Chemistry.

[96]  Y. Shyr,et al.  Dysregulated transcription across diverse cancer types reveals the importance of RNA-binding protein in carcinogenesis , 2015, BMC Genomics.

[97]  P. Herrlich,et al.  Signal-dependent regulation of splicing via phosphorylation of Sam68 , 2002, Nature.

[98]  A. Mele,et al.  Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer , 2014, eLife.

[99]  J. Keene,et al.  Post-transcriptional RNA regulons affecting cell cycle and proliferation. , 2014, Seminars in cell & developmental biology.

[100]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[101]  Claude C. Warzecha,et al.  ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. , 2009, Molecular cell.

[102]  Ke Ma,et al.  LARP7 is a potential tumor suppressor gene in gastric cancer , 2012, Laboratory Investigation.

[103]  Howard Y. Chang,et al.  irCLIP platform for efficient characterization of protein–RNA interactions , 2016, Nature Methods.

[104]  Norman E. Davey,et al.  Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins , 2012, Cell.

[105]  J. Richter,et al.  CPEB1 Mediates Epithelial-to-Mesenchyme Transition and Breast Cancer Metastasis , 2015, Oncogene.

[106]  Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state , 2014 .

[107]  Sol Katzman,et al.  RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation. , 2016, The Journal of clinical investigation.

[108]  A. D’Ambrogio,et al.  Translational control of cell growth and malignancy by the CPEBs , 2013, Nature Reviews Cancer.

[109]  Jeroen Krijgsveld,et al.  Comprehensive Identification of RNA-Binding Domains in Human Cells , 2016, Molecular cell.

[110]  Lin Zhang,et al.  Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells. , 2010, Cancer research.

[111]  C. Brennan,et al.  Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas , 2011, The EMBO journal.

[112]  Jiri Bartek,et al.  Replication stress links structural and numerical cancer chromosomal instability , 2013, Nature.

[113]  L. Penalva,et al.  The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs , 2011, RNA biology.

[114]  T. Hansen,et al.  IMP3 RNP safe houses prevent miRNA-directed HMGA2 mRNA decay in cancer and development. , 2014, Cell reports.

[115]  Dominic Grün,et al.  In vivo and transcriptome-wide identification of RNA binding protein target sites. , 2011, Molecular cell.

[116]  K. Miyazawa,et al.  Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) Suppress Cancer Cell Motility via Different Mechanisms* , 2014, The Journal of Biological Chemistry.

[117]  H. Will,et al.  The RNA-binding protein La contributes to cell proliferation and CCND1 expression , 2011, Oncogene.

[118]  Gavin D. Meredith,et al.  LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans , 2015, Genes & development.

[119]  K. Mowry,et al.  Principles and roles of mRNA localization in animal development , 2012, Development.

[120]  P. Meltzer,et al.  Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma. , 2012, Blood.

[121]  Nicholas C. Flytzanis,et al.  An EMT–Driven Alternative Splicing Program Occurs in Human Breast Cancer and Modulates Cellular Phenotype , 2011, PLoS genetics.

[122]  Tomohiko Ichikawa,et al.  MicroRNA-26a/b directly regulate La-related protein 1 and inhibit cancer cell invasion in prostate cancer. , 2015, International journal of oncology.

[123]  Bernd Fischer,et al.  RNA-binding proteins in Mendelian disease. , 2013, Trends in genetics : TIG.

[124]  M. Gorospe,et al.  RNA-binding protein HuR enhances p53 translation in response to ultraviolet light irradiation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[125]  J. Valcárcel,et al.  Tumor suppressor properties of the splicing regulatory factor RBM10 , 2016, RNA biology.

[126]  C. Will,et al.  The Spliceosome: Design Principles of a Dynamic RNP Machine , 2009, Cell.

[127]  M. Rosbash,et al.  TRIBE: Hijacking an RNA-Editing Enzyme to Identify Cell-Specific Targets of RNA-Binding Proteins , 2016, Cell.

[128]  K. Lukong,et al.  Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis , 2008, Oncogene.

[129]  M. Gorospe,et al.  The Oncogenic RNA-Binding Protein Musashi1 Is Regulated by HuR via mRNA Translation and Stability in Glioblastoma Cells , 2012, Molecular Cancer Research.

[130]  T. Golub,et al.  Impaired microRNA processing enhances cellular transformation and tumorigenesis , 2007, Nature Genetics.

[131]  M. Gorospe,et al.  Antiapoptotic function of RNA‐binding protein HuR effected through prothymosin α , 2005, The EMBO journal.

[132]  M. Assanah,et al.  HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer , 2010, Nature.

[133]  N. Chow,et al.  Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer , 2015, British Journal of Cancer.

[134]  M. Ares,et al.  Context-dependent control of alternative splicing by RNA-binding proteins , 2014, Nature Reviews Genetics.

[135]  Kotb Abdelmohsen,et al.  miR-519 suppresses tumor growth by reducing HuR levels , 2010, Cell cycle.

[136]  Jeffrey Wilusz,et al.  The highways and byways of mRNA decay , 2007, Nature Reviews Molecular Cell Biology.

[137]  S. Miyano,et al.  Identification of RNA-Binding Protein LARP4B as a Tumor Suppressor in Glioma. , 2016, Cancer research.

[138]  T. Hyslop,et al.  Identification of ASF/SF2 as a critical, allele-specific effector of the cyclin D1b oncogene. , 2010, Cancer research.

[139]  F. Orso,et al.  The RNA-binding protein ESRP1 promotes human colorectal cancer progression , 2016, Oncotarget.

[140]  P. Howe,et al.  Identification of an mRNP complex regulating tumorigenesis at the translational elongation step. , 2011, Molecular cell.

[141]  C. Chalfant,et al.  The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x , 2007, The Journal of cell biology.

[142]  A. Rustgi,et al.  IMP1 promotes tumor growth, dissemination and a tumor-initiating cell phenotype in colorectal cancer cell xenografts. , 2013, Carcinogenesis.

[143]  D. Benjamin,et al.  mRNA stability and cancer: an emerging link? , 2007, Expert opinion on biological therapy.

[144]  Jun Yao,et al.  Tumor-Specific Isoform Switch of the Fibroblast Growth Factor Receptor 2 Underlies the Mesenchymal and Malignant Phenotypes of Clear Cell Renal Cell Carcinomas , 2013, Clinical Cancer Research.

[145]  J. Valcárcel,et al.  The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing. , 2000, Molecular cell.

[146]  Kotb Abdelmohsen,et al.  Phosphorylation of HuR by Chk2 regulates SIRT1 expression. , 2007, Molecular cell.

[147]  Michael R Green,et al.  Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. , 2005, Molecular cell.

[148]  P. Lagarde,et al.  Unr, a cytoplasmic RNA-binding protein with cold-shock domains, is involved in control of apoptosis in ES and HuH7 cells , 2007, Oncogene.

[149]  M. Gorospe,et al.  Translational Repression by RNA-Binding Protein TIAR , 2006, Molecular and Cellular Biology.

[150]  P. Provero,et al.  Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation. , 2016, Cancer research.

[151]  Amber L. Wells,et al.  Regulation of local expression of cell adhesion and motility-related mRNAs in breast cancer cells by IMP1/ZBP1 , 2012, Journal of Cell Science.

[152]  Yang Wang,et al.  Engineering splicing factors with designed specificities , 2009, Nature Methods.

[153]  R. Strausberg,et al.  Altered Expression and Splicing of ESRP1 in Malignant Melanoma Correlates with Epithelial–Mesenchymal Status and Tumor-Associated Immune Cytolytic Activity , 2016, Cancer Immunology Research.

[154]  Abigail J. Deloria,et al.  Epithelial splicing regulatory protein 1 and 2 paralogues correlate with splice signatures and favorable outcome in human colorectal cancer , 2016, Oncotarget.

[155]  R. Carstens,et al.  Exo70 isoform switching upon epithelial-mesenchymal transition mediates cancer cell invasion. , 2013, Developmental cell.

[156]  Cathy H. Wu,et al.  Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing , 2015, Proceedings of the National Academy of Sciences.

[157]  Masato Nagino,et al.  let-7 regulates Dicer expression and constitutes a negative feedback loop. , 2008, Carcinogenesis.

[158]  A. Krainer,et al.  Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC. , 2012, Cell reports.

[159]  P. Northcott,et al.  The RNA-binding protein Musashi1 affects medulloblastoma growth via a network of cancer-related genes and is an indicator of poor prognosis. , 2012, The American journal of pathology.

[160]  L. Shkreta,et al.  Defective control of pre–messenger RNA splicing in human disease , 2016, The Journal of cell biology.

[161]  S. Gerstberger,et al.  A census of human RNA-binding proteins , 2014, Nature Reviews Genetics.

[162]  Angela Nakauka-Ddamba,et al.  Transformation of the intestinal epithelium by the MSI2 RNA binding protein , 2015, Nature Communications.

[163]  A. Hinnebusch,et al.  Translational control by 5′-untranslated regions of eukaryotic mRNAs , 2016, Science.

[164]  J. Flanagan,et al.  APC Is an RNA-Binding Protein, and Its Interactome Provides a Link to Neural Development and Microtubule Assembly , 2014, Cell.

[165]  H. Gautrey,et al.  SRSF3 and hnRNP H1 regulate a splicing hotspot of HER2 in breast cancer cells , 2015, RNA biology.

[166]  B. Séraphin,et al.  Identification and characterization of human Mex-3 proteins, a novel family of evolutionarily conserved RNA-binding proteins differentially localized to processing bodies , 2007, Nucleic acids research.

[167]  R. Schneider,et al.  mRNA decay factor AUF1 maintains normal aging, telomere maintenance, and suppression of senescence by activation of telomerase transcription. , 2012, Molecular cell.

[168]  T. Skorski,et al.  Downregulation of BRCA1 protein in BCR-ABL1 leukemia cells depends on stress-triggered TIAR-mediated suppression of translation , 2014, Cell cycle.

[169]  R. Hartley,et al.  MicroRNA-125a represses cell growth by targeting HuR in breast cancer , 2009, RNA biology.

[170]  R. Paro,et al.  The RNA Binding Protein IMP2 Preserves Glioblastoma Stem Cells by Preventing let-7 Target Gene Silencing. , 2016, Cell reports.

[171]  P. Jordan,et al.  Antagonistic SR proteins regulate alternative splicing of tumor-related Rac1b downstream of the PI3-kinase and Wnt pathways. , 2009, Human molecular genetics.

[172]  Xiongbin Lu,et al.  The ATM kinase induces microRNA biogenesis in the DNA damage response. , 2011, Molecular cell.

[173]  R. Hartley,et al.  HuR contributes to cyclin E1 deregulation in MCF-7 breast cancer cells. , 2006, Cancer research.

[174]  G. Delsol,et al.  A new player in oncogenesis: AUF1/hnRNPD overexpression leads to tumorigenesis in transgenic mice. , 2002, Cancer research.

[175]  John T. Powers,et al.  Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models. , 2014, Cancer cell.

[176]  Tsung-Cheng Chang,et al.  Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins , 2016, Cell.

[177]  Wei Li,et al.  CFIm25 links Alternative Polyadenylation to Glioblastoma Tumor Suppression , 2014, Nature.

[178]  J. Eberwine,et al.  Immunoprecipitation of mRNA-protein complexes , 2006, Nature Protocols.

[179]  Seong-Jun Cho,et al.  Glycogen synthase kinase 3 promotes p53 mRNA translation via phosphorylation of RNPC1 , 2013, Genes & development.

[180]  Qing Wang,et al.  Stabilization of Snail by HuR in the process of hydrogen peroxide induced cell migration. , 2007, Biochemical and biophysical research communications.

[181]  S. Srikantan,et al.  HuR recruits let-7/RISC to repress c-Myc expression. , 2009, Genes & development.

[182]  R. Elkon,et al.  Alternative cleavage and polyadenylation: extent, regulation and function , 2013, Nature Reviews Genetics.

[183]  P. Schirmacher,et al.  Overexpression of far upstream element binding proteins: A mechanism regulating proliferation and migration in liver cancer cells , 2009, Hepatology.

[184]  M. Gorospe,et al.  Posttranscriptional Derepression of GADD45α by Genotoxic Stress , 2006 .

[185]  C. Sette,et al.  The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells , 2007, Oncogene.

[186]  G. Brewer,et al.  Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation , 2007, Nature Structural &Molecular Biology.

[187]  Gabriele Varani,et al.  RNA is rarely at a loss for companions; as soon as RNA , 2008 .

[188]  A. Ridley,et al.  The RNA‐binding protein LARP4 regulates cancer cell migration and invasion , 2016, Cytoskeleton.

[189]  Edward L Huttlin,et al.  Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5′TOP mRNA translation , 2014, Genes & development.

[190]  Charles R. Tessier,et al.  Mammary Tumor Induction in Transgenic Mice Expressing an RNA-Binding Protein , 2004, Cancer Research.

[191]  G. Dreyfuss,et al.  Messenger-RNA-binding proteins and the messages they carry , 2002, Nature Reviews Molecular Cell Biology.

[192]  C. Zeng,et al.  Translational Repression of Human Matrix Metalloproteinases-13 by an Alternatively Spliced Form of T-cell-restricted Intracellular Antigen-related Protein (TIAR)* , 2003, The Journal of Biological Chemistry.

[193]  Wensheng Yan,et al.  RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript. , 2006, Genes & development.

[194]  Camille Stephan-Otto Attolini,et al.  Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells. , 2017, Cell stem cell.

[195]  M. Gorospe,et al.  RNA-binding protein HuR mediates cytoprotection through stimulation of XIAP translation , 2011, Oncogene.

[196]  M. Rosenfeld,et al.  The RNA-binding Protein KSRP Promotes the Biogenesis of a Subset of miRNAs , 2016 .

[197]  J. Priess,et al.  Translational Regulators Maintain Totipotency in the Caenorhabditis elegans Germline , 2006, Science.

[198]  H. Chi,et al.  Tristetraprolin Limits Inflammatory Cytokine Production in Tumor-Associated Macrophages in an mRNA Decay-Independent Manner. , 2015, Cancer research.

[199]  Guodong Yang,et al.  E2F1 and RNA binding protein QKI comprise a negative feedback in the cell cycle regulation , 2011, Cell cycle.

[200]  M. Rossi,et al.  miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-β-Induced Epithelial-to-Mesenchymal Transition. , 2016, Cell reports.

[201]  Huafeng Zhang,et al.  Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1 , 2014, Nature Communications.

[202]  Jun-Yuan Ji,et al.  Pumilio facilitates miRNA regulation of the E2F3 oncogene. , 2012, Genes & development.

[203]  G. Pinna,et al.  Post-transcriptional regulation of cyclins D1, D3 and G1 and proliferation of human cancer cells depend on IMP-3 nuclear localization , 2014, Oncogene.

[204]  Robert Castelo,et al.  Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition. , 2005, Molecular cell.

[205]  M. Roizen,et al.  Hallmarks of Cancer: The Next Generation , 2012 .

[206]  N. Sonenberg,et al.  Targeting the translation machinery in cancer , 2015, Nature Reviews Drug Discovery.

[207]  Dan Chen,et al.  The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression. , 2014, Cancer cell.

[208]  M. Korc,et al.  Epithelial Splicing Regulatory Protein 1 is a Favorable Prognostic Factor in Pancreatic Cancer that Attenuates Pancreatic Metastases , 2013, Oncogene.

[209]  Yonghong Xiao,et al.  STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA. , 2012, Genes & development.

[210]  Ju-Seog Lee,et al.  LIN28B promotes growth and tumorigenesis of the intestinal epithelium via Let-7 , 2013, Genes & development.

[211]  J. Manley,et al.  Loss of splicing factor ASF/SF2 induces G2 cell cycle arrest and apoptosis, but inhibits internucleosomal DNA fragmentation. , 2005, Genes & development.

[212]  W. Foulkes,et al.  DICER1: mutations, microRNAs and mechanisms , 2014, Nature Reviews Cancer.

[213]  Fatima Al-Shahrour,et al.  Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia , 2010, Nature Medicine.

[214]  E. Jankowsky,et al.  Specificity and nonspecificity in RNA–protein interactions , 2015, Nature Reviews Molecular Cell Biology.

[215]  J. Manley,et al.  Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. , 2010, Genes & development.

[216]  P. Howe,et al.  The La protein counteracts cisplatin-induced cell death by stimulating protein synthesis of anti-apoptotic factor Bcl2 , 2016, Oncotarget.

[217]  H. Gabra,et al.  The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration , 2010, Nucleic acids research.

[218]  P. Pandolfi,et al.  eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression , 2010, Proceedings of the National Academy of Sciences.

[219]  Anne E Willis,et al.  Members of the poly (rC) binding protein family stimulate the activity of the c-myc internal ribosome entry segment in vitro and in vivo , 2003, Oncogene.

[220]  Ju-Seog Lee,et al.  LIN28B promotes colon cancer progression and metastasis. , 2011, Cancer research.

[221]  Gretchen M. Williams,et al.  DICER1 Mutations in Familial Pleuropulmonary Blastoma , 2009, Science.

[222]  R. Stallings,et al.  LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression , 2012, Nature Genetics.

[223]  Mihaela Zavolan,et al.  Genome-wide analysis of pre-mRNA 3' end processing reveals a decisive role of human cleavage factor I in the regulation of 3' UTR length. , 2012, Cell reports.

[224]  Yusuke Nakamura,et al.  Increased Expression of Insulin-like Growth Factor-II Messenger RNA–Binding Protein 1 Is Associated with Tumor Progression in Patients with Lung Cancer , 2007, Clinical Cancer Research.

[225]  Replication stress links structural and numerical cancer chromosomal instability (vol 494, pg 492, 2013) , 2013 .

[226]  A. Krainer,et al.  The gene encoding the splicing factor SF2/ASF is a proto-oncogene , 2007, Nature Structural &Molecular Biology.

[227]  Myriam Gorospe,et al.  Role of the RNA-binding protein HuR in colon carcinogenesis , 2003, Oncogene.

[228]  F. Nielsen,et al.  RNA‐binding IMPs promote cell adhesion and invadopodia formation , 2006, The EMBO journal.

[229]  S. Janga,et al.  Dissecting the expression landscape of RNA-binding proteins in human cancers , 2014, Genome Biology.

[230]  Andreas R. Gruber,et al.  Cleavage factor Im is a key regulator of 3′ UTR length , 2012, RNA biology.

[231]  S. Richard,et al.  Emerging Roles of Disordered Sequences in RNA-Binding Proteins. , 2015, Trends in biochemical sciences.

[232]  Dimitrios Iliopoulos,et al.  Lin28A and Lin28B Inhibit let-7 MicroRNA Biogenesis by Distinct Mechanisms , 2011, Cell.

[233]  Luigi Coppola,et al.  Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma. , 2011, Cancer research.

[234]  S. Srikantan,et al.  miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels , 2008, Proceedings of the National Academy of Sciences.

[235]  Kotb Abdelmohsen,et al.  PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity , 2014, Nature Communications.