Skip to main content

Non-coding RNAs Functioning in Colorectal Cancer Stem Cells

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 937))

Abstract

In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main signaling pathways involved in the homeostasis of colorectal (CRC) stem cells are the Wnt, Notch, Sonic Hedgehog, and Bone Morfogenic Protein (BMP) pathways, which are mostly responsible for all the features that have been widely referred to stem cells. The same pathways have been identified in colorectal cancer stem cells (CRCSCs), conferring a more aggressive phenotype compared to non-stem CRC cells. Recently, several evidences suggested that non-coding RNAs (ncRNAs) may play a crucial role in the regulation of different biological mechanisms in CRC, by modulating the expression of critical stem cell transcription factors that have been found active in CSCs. In this chapter, we will discuss the involvement of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in stemness acquisition and maintenance by CRCSCs, through the regulation of pathways modulating the CSC phenotype and growth, carcinogenesis, differentiation, and epithelial to mesenchymal transition (EMT).

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  PubMed  Google Scholar 

  3. Marin JJ, Sanchez de Medina F, Castano B, Bujanda L, Romero MR, Martinez-Augustin O, et al. Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer. Drug Metab Rev. 2012;44(2):148–72.

    Article  CAS  PubMed  Google Scholar 

  4. Skvortsova I, Debbage P, Kumar V, Skvortsov S. Radiation resistance: cancer stem cells (CSCs) and their enigmatic pro-survival signaling. Semin Cancer Biol. 2015;35:39–44.

    Article  CAS  PubMed  Google Scholar 

  5. Raza U, Zhang JD, Sahin O. MicroRNAs: master regulators of drug resistance, stemness, and metastasis. J Mol Med (Berl). 2014;92(4):321–36.

    Article  CAS  Google Scholar 

  6. Sun X, Jiao X, Pestell TG, Fan C, Qin S, Mirabelli E, et al. MicroRNAs and cancer stem cells: the sword and the shield. Oncogene. 2014;33(42):4967–77.

    Article  CAS  PubMed  Google Scholar 

  7. Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355(12):1253–61.

    Article  CAS  PubMed  Google Scholar 

  8. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.

    Article  CAS  PubMed  Google Scholar 

  9. Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med. 2007;58:267–84. doi:10.1146/annurev.med.58.062105.204854.

    Article  CAS  PubMed  Google Scholar 

  10. Medema JP, Vermeulen L. Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature. 2011;474(7351):318–26.

    Article  CAS  PubMed  Google Scholar 

  11. Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells–old concepts, new insights. Cell Death Differ. 2008;15(6):947–58.

    Article  CAS  PubMed  Google Scholar 

  12. Lechler T, Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature. 2005;437(7056):275–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006;66(19):9339–44.

    Article  CAS  PubMed  Google Scholar 

  14. Gostjeva EV, Thilly WG. Stem cell stages and the origins of colon cancer: a multidisciplinary perspective. Stem Cell Rev. 2005;1(3):243–51.

    Article  PubMed  Google Scholar 

  15. Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene. 2004;23(43):7274–82.

    Article  CAS  PubMed  Google Scholar 

  16. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8(10):755–68.

    Article  CAS  PubMed  Google Scholar 

  17. Soltysova A, Altanerova V, Altaner C. Cancer stem cells. Neoplasma. 2005;52(6):435–40.

    CAS  PubMed  Google Scholar 

  18. Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S, et al. Targeting miRNAs involved in cancer stem cell and EMT regulation: an emerging concept in overcoming drug resistance. Drug Resist Updat. 2010;13(4-5):109–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730–7.

    Article  CAS  PubMed  Google Scholar 

  20. Davies EJ, Marsh V, Clarke AR. Origin and maintenance of the intestinal cancer stem cell. Mol Carcinog. 2011;50(4):254–63.

    Article  CAS  PubMed  Google Scholar 

  21. Todaro M, Francipane MG, Medema JP, Stassi G. Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 2010;138(6):2151–62.

    Article  CAS  PubMed  Google Scholar 

  22. Kosinski C, Li VS, Chan AS, Zhang J, Ho C, Tsui WY, et al. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci U S A. 2007;104(39):15418–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer. 2010;103(3):382–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Finkel T, Serrano M, Blasco MA. The common biology of cancer and ageing. Nature. 2007;448(7155):767–74.

    Article  CAS  PubMed  Google Scholar 

  25. Moitra K. Overcoming multidrug resistance in cancer stem cells. Biomed Res Int. 2015;2015:635745.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Cherciu I, Barbalan A, Pirici D, Margaritescu C, Saftoiu A. Stem cells, colorectal cancer and cancer stem cell markers correlations. Curr Health Sci J. 2014;40(3):153–61.

    PubMed  PubMed Central  Google Scholar 

  27. Fevr T, Robine S, Louvard D, Huelsken J. Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol Cell Biol. 2007;27(21):7551–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, et al. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol. 2009;7(6):e1000121.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Brabletz S, Schmalhofer O, Brabletz T. Gastrointestinal stem cells in development and cancer. J Pathol. 2009;217(2):307–17.

    Article  CAS  PubMed  Google Scholar 

  30. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275(5307):1787–90.

    Article  CAS  PubMed  Google Scholar 

  31. Miele L. Notch signaling. Clin Cancer Res. 2006;12(4):1074–9.

    Article  CAS  PubMed  Google Scholar 

  32. Amini S, Fathi F, Mobalegi J, Sofimajidpour H, Ghadimi T. The expressions of stem cell markers: Oct4, Nanog, Sox2, nucleostemin, Bmi, Zfx, Tcl1, Tbx3, Dppa4, and Esrrb in bladder, colon, and prostate cancer, and certain cancer cell lines. Anat Cell Biol. 2014;47(1):1–11. doi:10.5115/acb.2014.47.1.1.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Miele L, Osborne B. Arbiter of differentiation and death: notch signaling meets apoptosis. J Cell Physiol. 1999;181(3):393–409.

    Article  CAS  PubMed  Google Scholar 

  34. Ronchini C, Capobianco AJ. Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol. 2001;21(17):5925–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chen Y, Fischer WH, Gill GN. Regulation of the ERBB-2 promoter by RBPJkappa and NOTCH. J Biol Chem. 1997;272(22):14110–4.

    Article  CAS  PubMed  Google Scholar 

  36. Wang Z, Li Y, Kong D, Sarkar FH. The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Curr Drug Targets. 2010;11(6):745–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Leethanakul C, Patel V, Gillespie J, Pallente M, Ensley JF, Koontongkaew S, et al. Distinct pattern of expression of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays. Oncogene. 2000;19(28):3220–4.

    Article  CAS  PubMed  Google Scholar 

  38. Kessler M, Hoffmann K, Brinkmann V, Thieck O, Jackisch S, Toelle B, et al. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat Commun. 2015;6:8989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Su J, Wu S, Wu H, Li L, Guo T. CD44 is functionally crucial for driving lung cancer stem cells metastasis through Wnt/beta-catenin-FoxM1-Twist signaling. Mol Carcinog. 2015. doi:10.1002/mc.22443.

    Google Scholar 

  40. Yang K, Wang X, Zhang H, Wang Z, Nan G, Li Y, et al. The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies. Lab Invest. 2015.

    Google Scholar 

  41. Li JL, Sainson RC, Oon CE, Turley H, Leek R, Sheldon H, et al. DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo. Cancer Res. 2011;71(18):6073–83.

    Article  CAS  PubMed  Google Scholar 

  42. McAuliffe SM, Morgan SL, Wyant GA, Tran LT, Muto KW, Chen YS, et al. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc Natl Acad Sci U S A. 2012;109(43):E2939–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Huang B, Jolly MK, Lu M, Tsarfaty I, Ben-Jacob E, Onuchic JN. Modeling the transitions between collective and solitary migration phenotypes in cancer metastasis. Sci Rep. 2015;5:17379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Li P, Yang R, Gao WQ. Contributions of epithelial-mesenchymal transition and cancer stem cells to the development of castration resistance of prostate cancer. Mol Cancer. 2014;13:55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7(6):415–28.

    Article  CAS  PubMed  Google Scholar 

  46. Wu Y, Zhou BP. Inflammation: a driving force speeds cancer metastasis. Cell Cycle. 2009;8(20):3267–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM. MicroRNA expression and function in cancer. Trends Mol Med. 2006;12(12):580–7.

    Article  CAS  PubMed  Google Scholar 

  48. Sakaki-Yumoto M, Katsuno Y, Derynck R. TGF-beta family signaling in stem cells. Biochim Biophys Acta. 2013;1830(2):2280–96.

    Article  CAS  PubMed  Google Scholar 

  49. Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16(12):3488–98.

    Article  PubMed  Google Scholar 

  50. Moran VA, Perera RJ, Khalil AM. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res. 2012;40(14):6391–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ohnuki M, Tanabe K, Sutou K, Teramoto I, Sawamura Y, Narita M, et al. Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential. Proc Natl Acad Sci U S A. 2014;111(34):12426–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Martin L, Chang HY. Uncovering the role of genomic “dark matter” in human disease. J Clin Invest. 2012;122(5):1589–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Caruso S, Bazan V, Rolfo C, Insalaco L, Fanale D, Bronte G, et al. MicroRNAs in colorectal cancer stem cells: new regulators of cancer stemness? Oncogenesis. 2012;1:e32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Monzo M, Navarro A, Bandres E, Artells R, Moreno I, Gel B, et al. Overlapping expression of microRNAs in human embryonic colon and colorectal cancer. Cell Res. 2008;18(8):823–33.

    Article  CAS  PubMed  Google Scholar 

  55. Yu Y, Kanwar SS, Patel BB, Oh PS, Nautiyal J, Sarkar FH, et al. MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFbetaR2) in colon cancer cells. Carcinogenesis. 2012;33(1):68–76.

    Article  CAS  PubMed  Google Scholar 

  56. Yu Y, Nangia-Makker P, Farhana L, S GR, Levi E, Majumdar AP. miR-21 and miR-145 cooperation in regulation of colon cancer stem cells. Mol Cancer. 2015;14:98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Jahid S, Sun J, Edwards RA, Dizon D, Panarelli NC, Milsom JW, et al. miR-23a promotes the transition from indolent to invasive colorectal cancer. Cancer Discov. 2012;2(6):540–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Saarikangas J, Mattila PK, Varjosalo M, Bovellan M, Hakanen J, Calzada-Wack J, et al. Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia. J Cell Sci. 2011;124(Pt 8):1245–55.

    Article  CAS  PubMed  Google Scholar 

  59. Sancho R, Jandke A, Davis H, Diefenbacher ME, Tomlinson I, Behrens A. F-box and WD repeat domain-containing 7 regulates intestinal cell lineage commitment and is a haploinsufficient tumor suppressor. Gastroenterology. 2010;139(3):929–41.

    Article  CAS  PubMed  Google Scholar 

  60. Babaei-Jadidi R, Li N, Saadeddin A, Spencer-Dene B, Jandke A, Muhammad B, et al. FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. J Exp Med. 2011;208(2):295–312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Siemens H, Jackstadt R, Kaller M, Hermeking H. Repression of c-Kit by p53 is mediated by miR-34 and is associated with reduced chemoresistance, migration and stemness. Oncotarget. 2013;4(9):1399–415.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Bu P, Chen KY, Chen JH, Wang L, Walters J, Shin YJ, et al. A microRNA miR-34a-regulated bimodal switch targets Notch in colon cancer stem cells. Cell Stem Cell. 2013;12(5):602–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Neumuller RA, Knoblich JA. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev. 2009;23(23):2675–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Dey-Guha I, Wolfer A, Yeh AC, J GA, Darp R, Leon E, et al. Asymmetric cancer cell division regulated by AKT. Proc Natl Acad Sci U S A. 2011;108(31):12845–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. O’Brien CA, Kreso A, Ryan P, Hermans KG, Gibson L, Wang Y, et al. ID1 and ID3 regulate the self-renewal capacity of human colon cancer-initiating cells through p21. Cancer Cell. 2012;21(6):777–92.

    Article  PubMed  CAS  Google Scholar 

  66. Pine SR, Ryan BM, Varticovski L, Robles AI, Harris CC. Microenvironmental modulation of asymmetric cell division in human lung cancer cells. Proc Natl Acad Sci U S A. 2010;107(5):2195–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005;435(7044):959–63.

    Article  PubMed  CAS  Google Scholar 

  68. Yoo YD, Kwon YT. Molecular mechanisms controlling asymmetric and symmetric self-renewal of cancer stem cells. J Anal Sci Technol. 2015;6(1):28.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Hwang WL, Jiang JK, Yang SH, Huang TS, Lan HY, Teng HW, et al. MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells. Nat Cell Biol. 2014;16(3):268–80.

    Article  CAS  PubMed  Google Scholar 

  70. Lerner RG, Petritsch C. A microRNA-operated switch of asymmetric-to-symmetric cancer stem cell divisions. Nat Cell Biol. 2014;16(3):212–4.

    Article  CAS  PubMed  Google Scholar 

  71. Yu XF, Zou J, Bao ZJ, Dong J. miR-93 suppresses proliferation and colony formation of human colon cancer stem cells. World J Gastroenterol. 2011;17(42):4711–7. doi:10.3748/wjg.v17.i42.4711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Zheng L, Zhang Y, Liu Y, Zhou M, Lu Y, Yuan L, et al. MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer. J Transl Med. 2015;13:252.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Zhang Y, Zheng L, Huang J, Gao F, Lin X, He L, et al. MiR-124 Radiosensitizes human colorectal cancer cells by targeting PRRX1. PLoS ONE. 2014;9(4):e93917.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Chen J, Chen Y, Chen Z. MiR-125a/b regulates the activation of cancer stem cells in paclitaxel-resistant colon cancer. Cancer Invest. 2013;31(1):17–23. doi:10.3109/07357907.2012.743557.

    Article  CAS  PubMed  Google Scholar 

  75. Douville J, Beaulieu R, Balicki D. ALDH1 as a functional marker of cancer stem and progenitor cells. Stem Cells Dev. 2009;18(1):17–25.

    Article  CAS  PubMed  Google Scholar 

  76. Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, et al. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010;463(7277):103–7.

    Article  CAS  PubMed  Google Scholar 

  77. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hollier BG, Evans K, Mani SA. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia. 2009;14(1):29–43.

    Article  PubMed  Google Scholar 

  79. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009;11(12):1487–95.

    Article  CAS  PubMed  Google Scholar 

  80. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9(6):582–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283(22):14910–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pichler M, Ress AL, Winter E, Stiegelbauer V, Karbiener M, Schwarzenbacher D, et al. MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients. Br J Cancer. 2014;110(6):1614–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Ono H, Imoto I, Kozaki K, Tsuda H, Matsui T, Kurasawa Y, et al. SIX1 promotes epithelial-mesenchymal transition in colorectal cancer through ZEB1 activation. Oncogene. 2012;31(47):4923–34.

    Article  CAS  PubMed  Google Scholar 

  85. Lu YX, Yuan L, Xue XL, Zhou M, Liu Y, Zhang C, et al. Regulation of colorectal carcinoma stemness, growth, and metastasis by an miR-200c-Sox2-negative feedback loop mechanism. Clin Cancer Res. 2014;20(10):2631–42.

    Article  CAS  PubMed  Google Scholar 

  86. Ju SY, Chiou SH, Su Y. Maintenance of the stemness in CD44(+) HCT-15 and HCT-116 human colon cancer cells requires miR-203 suppression. Stem Cell Res. 2014;12(1):86–100.

    Article  CAS  PubMed  Google Scholar 

  87. Song B, Wang Y, Xi Y, Kudo K, Bruheim S, Botchkina GI, et al. Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene. 2009;28(46):4065–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Song B, Wang Y, Titmus MA, Botchkina G, Formentini A, Kornmann M, et al. Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer. 2010;9:96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Jones MF, Hara T, Francis P, Li XL, Bilke S, Zhu Y, et al. The CDX1-microRNA-215 axis regulates colorectal cancer stem cell differentiation. Proc Natl Acad Sci U S A. 2015;112(13):E1550–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhu R, Yang Y, Tian Y, Bai J, Zhang X, Li X, et al. Ascl2 knockdown results in tumor growth arrest by miRNA-302b-related inhibition of colon cancer progenitor cells. PLoS ONE. 2012;7(2):e32170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Xu XT, Xu Q, Tong JL, Zhu MM, Nie F, Chen X, et al. MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer. Br J Cancer. 2012;106(7):1320–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Fang Y, Gu X, Li Z, Xiang J, Chen Z. miR-449b inhibits the proliferation of SW1116 colon cancer stem cells through downregulation of CCND1 and E2F3 expression. Oncol Rep. 2013;30(1):399–406.

    CAS  PubMed  Google Scholar 

  93. Bitarte N, Bandres E, Boni V, Zarate R, Rodriguez J, Gonzalez-Huarriz M, et al. MicroRNA-451 is involved in the self-renewal, tumorigenicity, and chemoresistance of colorectal cancer stem cells. Stem Cells. 2011;29(11):1661–71.

    Article  CAS  PubMed  Google Scholar 

  94. Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol. 2010;12(5):468–76.

    Article  CAS  PubMed  Google Scholar 

  95. Zhang H, Li W, Nan F, Ren F, Wang H, Xu Y, et al. MicroRNA expression profile of colon cancer stem-like cells in HT29 adenocarcinoma cell line. Biochem Biophys Res Commun. 2011;404(1):273–8.

    Article  CAS  PubMed  Google Scholar 

  96. Vaiopoulos AG, Kostakis ID, Koutsilieris M, Papavassiliou AG. Colorectal cancer stem cells. Stem Cells. 2012;30(3):363–71.

    Article  CAS  PubMed  Google Scholar 

  97. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106(28):11667–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Wang G, Li Z, Zhao Q, Zhu Y, Zhao C, Li X, et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/beta-catenin signaling pathway. Oncol Rep. 2014;31(4):1839–45.

    CAS  PubMed  Google Scholar 

  100. Boo K, Bhin J, Jeon Y, Kim J, Shin HJ, Park JE, et al. Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells. Nat Commun. 2015;6:6810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Sheik Mohamed J, Gaughwin PM, Lim B, Robson P, Lipovich L. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA. 2010;16(2):324–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet. 2010;42(12):1113–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Gui X, Li H, Li T, Pu H, Lu D. Long noncoding RNA CUDR regulates HULC and beta-catenin to govern human liver stem cell malignant differentiation. Mol Ther. 2015.

    Google Scholar 

  104. Dragu DL, Necula LG, Bleotu C, Diaconu CC, Chivu-Economescu M. Therapies targeting cancer stem cells: current trends and future challenges. World J Stem Cells. 2015;7(9):1185–201.

    PubMed  PubMed Central  Google Scholar 

  105. Fanale D, Caruso S, Bazan V, Bronte G, Di Piazza F, Rolfo C et al. MicroRNAs in colorectal cancer drug resistance: shooters become targets. J Carcinog Mutag. 2013;04(02).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Russo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Fanale, D., Barraco, N., Listì, A., Bazan, V., Russo, A. (2016). Non-coding RNAs Functioning in Colorectal Cancer Stem Cells. In: Slaby, O., Calin, G. (eds) Non-coding RNAs in Colorectal Cancer. Advances in Experimental Medicine and Biology, vol 937. Springer, Cham. https://doi.org/10.1007/978-3-319-42059-2_5

Download citation

Publish with us

Policies and ethics