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Ribosomal proteins: insight into molecular roles and functions in hepatocellular carcinoma

Oncogene volume 37, pages 277–285 (2018)Cite this article

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Abstract

Ribosomes, which are important sites for the synthesis of proteins related to expression and transmission of genetic information in humans, have a complex structure and diverse functions. They consist of a variety of ribosomal proteins (RPs), ribosomal RNAs (rRNAs) and small nucleolar RNAs. Owing to the involvement of ribosomes in many important biological processes of cells, their major components, rRNAs and RPs, have an important role in human diseases, including the initiation and evolvement of malignancies. However, the main mechanisms underlying the involvement of ribosomes in cancer remain unclear. This review describes the crucial role of ribosomes in various common malignant tumors; in particular, it examines the effects of RPs, including S6, the receptor for activated C-kinase and RPS15A, on the development and progression of hepatocellular carcinoma.

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References

  1. Ruggero D, Pandolfi PP . Does the ribosome translate cancer? Nat Rev Cancer 2003; 3: 179–192.

    Article  CAS  PubMed  Google Scholar 

  2. Shenoy N, Kessel R, Bhagat TD, Bhattacharyya S, Yu Y, McMahon C et al. Alterations in the ribosomal machinery in cancer and hematologic disorders. J Hematol Oncol 2012; 5: 32.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Wang W, Nag S, Zhang X, Wang MH, Wang H, Zhou J et al. Ribosomal proteins and human diseases: pathogenesis, molecular mechanisms, and therapeutic implications. Med Res Rev 2015; 35: 225–285.

    PubMed  Google Scholar 

  4. Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M . The structure of the eukaryotic ribosome at 3.0 A resolution. Science 2011; 334: 1524–1529.

    CAS  PubMed  Google Scholar 

  5. Khatter H, Myasnikov AG, Natchiar SK, Klaholz BP . Structure of the human 80 S ribosome. Nature 2015; 520: 640–645.

    CAS  PubMed  Google Scholar 

  6. Brar GA, Weissman JS . Ribosome profiling reveals the what, when, where and how of protein synthesis. Nat Rev Mol Cell Biol 2015; 16: 651–664.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Nakhoul H, Ke J, Zhou X, Liao W, Zeng SX, Lu H . Ribosomopathies: mechanisms of disease. Clin Med Insights Blood Disorders 2014; 7: 7–16.

    CAS  PubMed  Google Scholar 

  8. Danilova N, Gazda HT . Ribosomopathies: how a common root can cause a tree of pathologies. Dis Models Mech 2015; 8: 1013–1026.

    CAS  Google Scholar 

  9. Teng T, Thomas G, Mercer CA . Growth control and ribosomopathies. Curr Opin Genet Dev 2013; 23: 63–71.

    CAS  PubMed  Google Scholar 

  10. Stumpf CR, Ruggero D . The cancerous translation apparatus. Curr Opin Genet Dev 2011; 21: 474–483.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Bruno PM, Liu Y, Park GY, Murai J, Koch CE, Eisen TJ et al. A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress. Nat Med 2017; 23: 461–471.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang C, Cigliano A, Jiang L, Li X, Fan B, Pilo MG et al. 4EBP1/eIF4E and p70S6K/RPS6 axes play critical and distinct roles in hepatocarcinogenesis driven by AKT and N-Ras proto-oncogenes in mice. Hepatology (Baltimore, MD) 2015; 61: 200–213.

    Google Scholar 

  13. Calvisi DF, Wang C, Ho C, Ladu S, Lee SA, Mattu S et al. Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology 2011; 140: 1071–1083.

    CAS  PubMed  Google Scholar 

  14. Guo Y, Wang W, Wang J, Feng J, Wang Q, Jin J et al. Receptor for activated C kinase 1 promotes hepatocellular carcinoma growth by enhancing mitogen-activated protein kinase kinase 7 activity. Hepatology (Baltimore, MD) 2013; 57: 140–151.

    CAS  Google Scholar 

  15. Ruan Y, Sun L, Hao Y, Wang L, Xu J, Zhang W et al. Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular carcinoma. J Clin Invest 2012; 122: 2554–2566.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Lian Z, Liu J, Li L, Li X, Tufan NL, Wu MC et al. Human S15a expression is upregulated by hepatitis B virus X protein. Mol Carcinog 2004; 40: 34–46.

    CAS  PubMed  Google Scholar 

  17. Xu M, Wang Y, Chen L, Pan B, Chen F, Fang Y et al. Down-regulation of ribosomal protein S15A mRNA with a short hairpin RNA inhibits human hepatic cancer cell growth in vitro. Gene 2014; 536: 84–89.

    CAS  PubMed  Google Scholar 

  18. Zeng M, Zheng M, Lu D, Wang J, Jiang W, Sha O . Anti-tumor activities and apoptotic mechanism of ribosome-inactivating proteins. Chin J Cancer 2015; 34: 325–334.

    CAS  PubMed  Google Scholar 

  19. Melnikov S, Ben-Shem A, Garreau de Loubresse N, Jenner L, Yusupova G, Yusupov M . One core, two shells: bacterial and eukaryotic ribosomes. Nat Struct Mol Biol 2012; 19: 560–567.

    CAS  PubMed  Google Scholar 

  20. Boisvert FM, van Koningsbruggen S, Navascues J, Lamond AI . The multifunctional nucleolus. Nat Rev Mol Cell Biol 2007; 8: 574–585.

    CAS  PubMed  Google Scholar 

  21. Gruschke S, Ott M . The polypeptide tunnel exit of the mitochondrial ribosome is tailored to meet the specific requirements of the organelle. BioEssays 2010; 32: 1050–1057.

    CAS  PubMed  Google Scholar 

  22. Desai N, Brown A, Amunts A, Ramakrishnan V . The structure of the yeast mitochondrial ribosome. Science 2017; 355: 528–531.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Ramesh M, Woolford JL Jr . Eukaryote-specific rRNA expansion segments function in ribosome biogenesis. RNA 2016; 22: 1153–1162.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Robledo S, Idol RA, Crimmins DL, Ladenson JH, Mason PJ, Bessler M . The role of human ribosomal proteins in the maturation of rRNA and ribosome production. RNA 2008; 14: 1918–1929.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Orelle C, Carlson ED, Szal T, Florin T, Jewett MC, Mankin AS . Protein synthesis by ribosomes with tethered subunits. Nature 2015; 524: 119–124.

    CAS  PubMed  Google Scholar 

  26. Zeng F, Chen Y, Remis J, Shekhar M, Phillips JC, Tajkhorshid E et al. Structural basis of co-translational quality control by ArfA and RF2 bound to ribosome. Nature 2017; 541: 554–557.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Hinnebusch AG, Lorsch JR . The mechanism of eukaryotic translation initiation: new insights and challenges. Cold Spring Harbor Perspect Biol 2012; 4: pii: a011544.

    PubMed  PubMed Central  Google Scholar 

  28. Orsolic I, Jurada D, Pullen N, Oren M, Eliopoulos AG, Volarevic S . The relationship between the nucleolus and cancer: current evidence and emerging paradigms. Semin Cancer Biol 2016; 37-38: 36–50.

    CAS  PubMed  Google Scholar 

  29. Ruggero D . Revisiting the nucleolus: from marker to dynamic integrator of cancer signaling. Sci Signal 2012; 5: pe38.

    PubMed  PubMed Central  Google Scholar 

  30. Volarevic S, Stewart MJ, Ledermann B, Zilberman F, Terracciano L, Montini E et al. Proliferation, but not growth, blocked by conditional deletion of 40 S ribosomal protein S6. Science 2000; 288: 2045–2047.

    CAS  PubMed  Google Scholar 

  31. Kim JH, You KR, Kim IH, Cho BH, Kim CY, Kim DG . Over-expression of the ribosomal protein L36a gene is associated with cellular proliferation in hepatocellular carcinoma. Hepatology (Baltimore, MD) 2004; 39: 129–138.

    CAS  Google Scholar 

  32. Donati G, Montanaro L, Derenzini M . Ribosome biogenesis and control of cell proliferation: p53 is not alone. Cancer Res 2012; 72: 1602–1607.

    CAS  PubMed  Google Scholar 

  33. Wang H, Zhao LN, Li KZ, Ling R, Li XJ, Wang L . Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer. BMC Cancer 2006; 6: 91.

    PubMed  PubMed Central  Google Scholar 

  34. Zhan Y, Melian NY, Pantoja M, Haines N, Ruohola-Baker H, Bourque CW et al. Dystroglycan and mitochondrial ribosomal protein L34 regulate differentiation in the Drosophila eye. PLoS One 2010; 5: e10488.

    PubMed  PubMed Central  Google Scholar 

  35. Da Costa L, Narla G, Willig TN, Peters LL, Parra M, Fixler J et al. Ribosomal protein S19 expression during erythroid differentiation. Blood 2003; 101: 318–324.

    CAS  PubMed  Google Scholar 

  36. He H, Sun Y . Ribosomal protein S27L is a direct p53 target that regulates apoptosis. Oncogene 2007; 26: 2707–2716.

    CAS  PubMed  Google Scholar 

  37. Jang CY, Lee JY, Kim J . RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis. FEBS Lett 2004; 560: 81–85.

    CAS  PubMed  Google Scholar 

  38. Hegde V, Wang M, Deutsch WA . Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE/Ref-1 and hOGG1. Biochemistry 2004; 43: 14211–14217.

    CAS  PubMed  Google Scholar 

  39. Kim J, Chubatsu LS, Admon A, Stahl J, Fellous R, Linn S . Implication of mammalian ribosomal protein S3 in the processing of DNA damage. J Biol Chem 1995; 270: 13620–13629.

    CAS  PubMed  Google Scholar 

  40. Yang ZY, Jiang H, Qu Y, Wei M, Yan M, Zhu ZG et al. Metallopanstimulin-1 regulates invasion and migration of gastric cancer cells partially through integrin beta4. Carcinogenesis 2013; 34: 2851–2860.

    CAS  PubMed  Google Scholar 

  41. Narla A, Ebert BL . Ribosomopathies: human disorders of ribosome dysfunction. Blood 2010; 115: 3196–3205.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Fumagalli S, Thomas G . The role of p53 in ribosomopathies. Semin Hematol 2011; 48: 97–105.

    CAS  PubMed  Google Scholar 

  43. Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I et al. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet 1999; 21: 169–175.

    CAS  PubMed  Google Scholar 

  44. Sutcliffe JE, Brown TR, Allison SJ, Scott PH, White RJ . Retinoblastoma protein disrupts interactions required for RNA polymerase III transcription. Mol Cell Biol 2000; 20: 9192–9202.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Donati G, Bertoni S, Brighenti E, Vici M, Trere D, Volarevic S et al. The balance between rRNA and ribosomal protein synthesis up- and downregulates the tumour suppressor p53 in mammalian cells. Oncogene 2011; 30: 3274–3288.

    CAS  PubMed  Google Scholar 

  46. Zhou X, Liao WJ, Liao JM, Liao P, Lu H . Ribosomal proteins: functions beyond the ribosome. J Mol Cell Biol 2015; 7: 92–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. van Riggelen J, Yetil A, Felsher DW . MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 2010; 10: 301–309.

    CAS  PubMed  Google Scholar 

  48. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87–108.

    PubMed  Google Scholar 

  49. Whittaker S, Marais R, Zhu AX . The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010; 29: 4989–5005.

    CAS  PubMed  Google Scholar 

  50. Shukla SK, Kumar V . Hepatitis B virus X protein and c-Myc cooperate in the upregulation of ribosome biogenesis and in cellular transformation. FEBS J 2012; 279: 3859–3871.

    CAS  PubMed  Google Scholar 

  51. Fatima G, Mathan G, Kumar V . The HBx protein of hepatitis B virus regulates the expression, intracellular distribution and functions of ribosomal protein S27a. J Gen Virol 2012; 93: 706–715.

    CAS  PubMed  Google Scholar 

  52. Raychaudhuri S, Fontanes V, Barat B, Dasgupta A . Activation of ribosomal RNA transcription by hepatitis C virus involves upstream binding factor phosphorylation via induction of cyclin D1. Cancer Res 2009; 69: 2057–2064.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Grewal SS, Li L, Orian A, Eisenman RN, Edgar BA . Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol 2005; 7: 295–302.

    CAS  PubMed  Google Scholar 

  54. Sollner-Webb B, Tower J . Transcription of cloned eukaryotic ribosomal RNA genes. Annu Rev Biochem 1986; 55: 801–830.

    CAS  PubMed  Google Scholar 

  55. Yu F, Shen X, Fan L, Yu Z . Analysis of histone modifications at human ribosomal DNA in liver cancer cell. Sci Rep 2015; 5: 18100.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Moss T, Langlois F, Gagnon-Kugler T, Stefanovsky V . A housekeeper with power of attorney: the rRNA genes in ribosome biogenesis. Cell Mol Life Sci 2007; 64: 29–49.

    CAS  PubMed  Google Scholar 

  57. Wang HD, Trivedi A, Johnson DL . Regulation of RNA polymerase I-dependent promoters by the hepatitis B virus X protein via activated Ras and TATA-binding protein. Mol Cell Biol 1998; 18: 7086–7094.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Ahuja R, Kapoor NR, Kumar V . The HBx oncoprotein of hepatitis B virus engages nucleophosmin to promote rDNA transcription and cellular proliferation. Biochim Biophys Acta 2015; 1853: 1783–1795.

    CAS  PubMed  Google Scholar 

  59. Gentilella A, Kozma SC, Thomas G . A liaison between mTOR signaling, ribosome biogenesis and cancer. Biochim Biophys Acta 2015; 1849: 812–820.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Zinzalla V, Stracka D, Oppliger W, Hall MN . Activation of mTORC2 by association with the ribosome. Cell 2011; 144: 757–768.

    CAS  PubMed  Google Scholar 

  61. Iadevaia V, Liu R, Proud CG . mTORC1 signaling controls multiple steps in ribosome biogenesis. Semin Cell Dev Biol 2014; 36: 113–120.

    CAS  PubMed  Google Scholar 

  62. Li W, Tan D, Zhang Z, Liang JJ, Brown RE . Activation of Akt-mTOR-p70S6K pathway in angiogenesis in hepatocellular carcinoma. Oncol Rep 2008; 20: 713–719.

    PubMed  Google Scholar 

  63. Magnuson B, Ekim B, Fingar DC . Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J 2012; 441: 1–21.

    CAS  PubMed  Google Scholar 

  64. Plas DR, Thomas G . Tubers and tumors: rapamycin therapy for benign and malignant tumors. Curr Opin Cell Biol 2009; 21: 230–236.

    CAS  PubMed  Google Scholar 

  65. Sahin F, Kannangai R, Adegbola O, Wang J, Su G, Torbenson M . mTOR and P70 S6 kinase expression in primary liver neoplasms. Clin Cancer Res 2004; 10: 8421–8425.

    CAS  PubMed  Google Scholar 

  66. Baba HA, Wohlschlaeger J, Cicinnati VR, Hilgard P, Lang H, Sotiropoulos GC et al. Phosphorylation of p70S6 kinase predicts overall survival in patients with clear margin-resected hepatocellular carcinoma. Liver Int 2009; 29: 399–405.

    CAS  PubMed  Google Scholar 

  67. Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY et al. Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma. J Biol Chem 2003; 278: 10824–10830.

    CAS  PubMed  Google Scholar 

  68. Leung TH, Yam JW, Chan LK, Ching YP, Ng IO . Deleted in liver cancer 2 suppresses cell growth via the regulation of the Raf-1-ERK1/2-p70S6K signalling pathway. Liver Int 2010; 30: 1315–1323.

    CAS  PubMed  Google Scholar 

  69. Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR et al. Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 1999; 17: 676–682.

    CAS  PubMed  Google Scholar 

  70. Sengupta J, Nilsson J, Gursky R, Spahn CM, Nissen P, Frank J . Identification of the versatile scaffold protein RACK1 on the eukaryotic ribosome by cryo-EM. Nat Struct Mol Biol 2004; 11: 957–962.

    CAS  PubMed  Google Scholar 

  71. McCahill A, Warwicker J, Bolger GB, Houslay MD, Yarwood SJ . The RACK1 scaffold protein: a dynamic cog in cell response mechanisms. Mol Pharmacol 2002; 62: 1261–1273.

    CAS  PubMed  Google Scholar 

  72. Wu J, Meng J, Du Y, Huang Y, Jin Y, Zhang J et al. RACK1 promotes the proliferation, migration and invasion capacity of mouse hepatocellular carcinoma cell line in vitro probably by PI3K/Rac1 signaling pathway. Biomed Pharmacother 2013; 67: 313–319.

    CAS  PubMed  Google Scholar 

  73. Wang WD, Wen Z, Ji W, Ma Y . RACK1 expression contributes to JNK activity, but JNK activity does not enhance RACK1 expression in hepatocellular carcinoma SMMC-7721 cells. Oncol Lett 2015; 9: 2767–2770.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhou S, Cao H, Zhao Y, Li X, Zhang J, Hou C et al. RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-alpha-induced ROS generation. Oncol Lett 2016; 12: 5303–5308.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhou T, Lv X, Guo X, Ruan B, Liu D, Ding R et al. RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis. Oncol Rep 2015; 33: 3006–3014.

    CAS  PubMed  Google Scholar 

  76. Akiyama N, Matsuo Y, Sai H, Noda M, Kizaka-Kondoh S . Identification of a series of transforming growth factor beta-responsive genes by retrovirus-mediated gene trap screening. Mol Cell Biol 2000; 20: 3266–3273.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Lavoie C, Tam R, Clark M, Lee H, Sonenberg N, Lasko P . Suppression of a temperature-sensitive cdc33 mutation of yeast by a multicopy plasmid expressing a Drosophila ribosomal protein. J Biol Chem 1994; 269: 14625–14630.

    CAS  PubMed  Google Scholar 

  78. Jimenez L, Becerra A, Landa A . Cloning, expression and partial characterization of a gene encoding the S15a ribosomal protein of Taenia solium. Parasitol Res 2004; 92: 414–420.

    PubMed  Google Scholar 

  79. Chen J, Wei Y, Feng Q, Ren L, He G, Chang W et al. Ribosomal protein S15A promotes malignant transformation and predicts poor outcome in colorectal cancer through misregulation of p53 signaling pathway. Int J Ocol 2016; 48: 1628–1638.

    CAS  Google Scholar 

  80. Song MJ, Jung CK, Park CH, Hur W, Choi JE, Bae SH et al. RPL36 as a prognostic marker in hepatocellular carcinoma. Pathol Int 2011; 61: 638–644.

    CAS  PubMed  Google Scholar 

  81. Kowalczyk P, Woszczynski M, Ostrowski J . Increased expression of ribosomal protein S2 in liver tumors, posthepactomized livers, and proliferating hepatocytes in vitro. Acta Biochim Pol 2002; 49: 615–624.

    CAS  PubMed  Google Scholar 

  82. Pogue-Geile K, Geiser JR, Shu M, Miller C, Wool IG, Meisler AI et al. Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. Mol Cell Biol 1991; 11: 3842–3849.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Kasai H, Nadano D, Hidaka E, Higuchi K, Kawakubo M, Sato TA et al. Differential expression of ribosomal proteins in human normal and neoplastic colorectum. J Histochem Cytochem 2003; 51: 567–574.

    CAS  PubMed  Google Scholar 

  84. Kobayashi T, Sasaki Y, Oshima Y, Yamamoto H, Mita H, Suzuki H et al. Activation of the ribosomal protein L13 gene in human gastrointestinal cancer. Int J Mol Med 2006; 18: 161–170.

    CAS  PubMed  Google Scholar 

  85. Huang CJ, Chien CC, Yang SH, Chang CC, Sun HL, Cheng YC et al. Faecal ribosomal protein L19 is a genetic prognostic factor for survival in colorectal cancer. J Cell Mol Med 2008; 12: 1936–1943.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Huang CJ, Yang SH, Lee CL, Cheng YC, Tai SY, Chien CC . Ribosomal protein S27-like in colorectal cancer: a candidate for predicting prognoses. PLoS One 2013; 8: e67043.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Guo X, Shi Y, Gou Y, Li J, Han S, Zhang Y et al. Human ribosomal protein S13 promotes gastric cancer growth through down-regulating p27(Kip1). J Cell Mol Med 2011; 15: 296–306.

    CAS  PubMed  Google Scholar 

  88. Wu Q, Gou Y, Wang Q, Jin H, Cui L, Zhang Y et al. Downregulation of RPL6 by siRNA inhibits proliferation and cell cycle progression of human gastric cancer cell lines. PLoS ONE 2011; 6: e26401.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Du J, Shi Y, Pan Y, Jin X, Liu C, Liu N et al. Regulation of multidrug resistance by ribosomal protein l6 in gastric cancer cells. Cancer Biol Ther 2005; 4: 242–247.

    CAS  PubMed  Google Scholar 

  90. Zhang Y, Shi Y, Li X, Du W, Luo G, Gou Y et al. Inhibition of the p53-MDM2 interaction by adenovirus delivery of ribosomal protein L23 stabilizes p53 and induces cell cycle arrest and apoptosis in gastric cancer. J Gene Med 2010; 12: 147–156.

    CAS  PubMed  Google Scholar 

  91. Shi Y, Zhai H, Wang X, Han Z, Liu C, Lan M et al. Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer cells by suppressing drug-induced apoptosis. Exp Cell Res 2004; 296: 337–346.

    CAS  PubMed  Google Scholar 

  92. Li C, Ge M, Yin Y, Luo M, Chen D . Silencing expression of ribosomal protein L26 and L29 by RNA interfering inhibits proliferation of human pancreatic cancer PANC-1 cells. Mol Cell Biochem 2012; 370: 127–139.

    CAS  PubMed  Google Scholar 

  93. Muro S, Miyake Y, Kato H, Tsutsumi K, Yamamoto K . Serum anti-60 S ribosomal protein L29 antibody as a novel prognostic marker for unresectable pancreatic cancer. Digestion 2015; 91: 164–173.

    CAS  PubMed  Google Scholar 

  94. Milosevic N, Kühnemuth B, Mühlberg L, Ripka S, Griesmann H, Lölkes C et al. Synthetic lethality screen identifies RPS6KA2 as modifier of epidermal growth factor receptor activity in pancreatic cancer. Neoplasia 2013; 15: 1354–1362.

    PubMed  PubMed Central  Google Scholar 

  95. Wei F, Ding L, Wei Z, Zhang Y, Li Y, Qinghua L et al. Ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells. Oncotarget 2016; 7: 85259–85272.

    PubMed  PubMed Central  Google Scholar 

  96. Ray S, Johnston R, Campbell DC, Nugent S, McDade SS, Waugh D et al. Androgens and estrogens stimulate ribosome biogenesis in prostate and breast cancer cells in receptor dependent manner. Gene 2013; 526: 46–53.

    CAS  PubMed  Google Scholar 

  97. Thakur A, Sun Y, Bollig A, Wu J, Biliran H, Banerjee S et al. Anti-invasive and antimetastatic activities of ribosomal protein S6 kinase 4 in breast cancer cells. Clin Cancer Res 2008; 14: 4427–4436.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Wang S, Huang J, He J, Wang A, Xu S, Huang S-F et al. RPL41, a small ribosomal peptide deregulated in tumors, is essential for mitosis and centrosome integrity. Neoplasia 2010; 12: 284–IN288.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Bee A, Ke Y, Forootan S, Lin K, Beesley C, Forrest SE et al. Ribosomal protein l19 is a prognostic marker for human prostate cancer. Clin Cancer Res 2006; 12: 2061–2065.

    CAS  PubMed  Google Scholar 

  100. Bee A, Brewer D, Beesley C, Dodson A, Forootan S, Dickinson T et al. siRNA knockdown of ribosomal protein gene RPL19 abrogates the aggressive phenotype of human prostate cancer. PLoS One 2011; 6: e22672.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Wang M, Hu Y, Stearns ME . RPS2: a novel therapeutic target in prostate cancer. J Exp Clin Cancer Res 2009; 28: 6.

    PubMed  PubMed Central  Google Scholar 

  102. Shen F, Yan C, Liu M, Feng Y, Chen Y . RACK1 promotes prostate cancer cell proliferation, invasion and metastasis. Mol Med Rep 2013; 8: 999–1004.

    CAS  PubMed  Google Scholar 

  103. McDonald JM, Pelloski CE, Ledoux A, Sun M, Raso G, Komaki R et al. Elevated phospho-S6 expression is associated with metastasis in adenocarcinoma of the lung. Clin Cancer Res 2008; 14: 7832–7837.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Yang M, Sun H, Wang H, Zhang S, Yu X, Zhang L . Down-regulation of ribosomal protein L22 in non-small cell lung cancer. Med Oncol 2013; 30: 646.

    PubMed  Google Scholar 

  105. Rao S, Lee SY, Gutierrez A, Perrigoue J, Thapa RJ, Tu Z et al. Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 2012; 120: 3764–3773.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Ni JQ, Liu LP, Hess D, Rietdorf J, Sun FL . Drosophila ribosomal proteins are associated with linker histone H1 and suppress gene transcription. Genes Dev 2006; 20: 1959–1973.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Lin KY, Tai C, Hsu JC, Li CF, Fang CL, Lai HC et al. Overexpression of nuclear protein kinase CK2 alpha catalytic subunit (CK2alpha) as a poor prognosticator in human colorectal cancer. PLoS One 2011; 6: e17193.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Siddiqui-Jain A, Drygin D, Streiner N, Chua P, Pierre F, O'Brien SE et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res 2010; 70: 10288–10298.

    CAS  PubMed  Google Scholar 

  109. Yang M, Sun H, He J, Wang H, Yu X, Ma L et al. Interaction of ribosomal protein L22 with casein kinase 2alpha: a novel mechanism for understanding the biology of non-small cell lung cancer. Oncol Rep 2014; 32: 139–144.

    CAS  PubMed  Google Scholar 

  110. Chan MW, Wei SH, Wen P, Wang Z, Matei DE, Liu JC et al. Hypermethylation of 18 S and 28 S ribosomal DNAs predicts progression-free survival in patients with ovarian cancer. Clin Cancer Res 2005; 11: 7376–7383.

    CAS  PubMed  Google Scholar 

  111. Tsofack SP, Meunier L, Sanchez L, Madore J, Provencher D, Mes-Masson AM et al. Low expression of the X-linked ribosomal protein S4 in human serous epithelial ovarian cancer is associated with a poor prognosis. BMC Cancer 2013; 13: 303.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Kim SH, Jang YH, Chau GC, Pyo S, Um SH . Prognostic significance and function of phosphorylated ribosomal protein S6 in esophageal squamous cell carcinoma. Mod Pathol 2013; 26: 327–335.

    CAS  PubMed  Google Scholar 

  113. Hagner PR, Mazan-Mamczarz K, Dai B, Balzer EM, Corl S, Martin SS et al. Ribosomal protein S6 is highly expressed in non-Hodgkin lymphoma and associates with mRNA containing a 5' terminal oligopyrimidine tract. Oncogene 2011; 30: 1531–1541.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the grants from the Natural Science Foundation of Zhejiang Province (LY17H160047), the National Natural Science Foundation of China(81201953, 81772628, 81703310) and the Research Found for the Doctoral Program of High Education of China from the Ministry of Education (20113321120003).

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  1. Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China

    X Xie, P Guo, H Yu & G Chen

  2. Research Center of Evidence-Based Medicine and Clinical Epidemiology, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China

    Y Wang

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Xie, X., Guo, P., Yu, H. et al. Ribosomal proteins: insight into molecular roles and functions in hepatocellular carcinoma. Oncogene 37, 277–285 (2018). https://doi.org/10.1038/onc.2017.343

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