Skip to main content

Advertisement

Log in

MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications

  • Review Article
  • Theme: siRNA and microRNA: From Target Validation to Therapy
  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are a class of endogenous non-protein-coding RNAs that function as important regulatory molecules by negatively regulating gene and protein expression via the RNA interference (RNAi) machinery. MiRNAs have been implicated to control a variety of cellular, physiological, and developmental processes. Aberrant expressions of miRNAs are connected to human diseases such as cancer. Cancer stem cells are a small subpopulation of cells identified in a variety of tumors that are capable of self-renewal and differentiation. Dysregulation of stem cell self-renewal is a likely requirement for the initiation and formation of cancer. Furthermore, cancer stem cells are a very likely cause of resistance to current cancer treatments, as well as relapse in cancer patients. Understanding the biology and pathways involved with cancer stem cells offers great promise for developing better cancer therapies, and might one day even provide a cure for cancer. Emerging evidence demonstrates that miRNAs are involved in cancer stem cell dysregulation. Recent studies also suggest that miRNAs play a critical role in carcinogenesis and oncogenesis by regulating cell proliferation and apoptosis as oncogenes or tumor suppressors, respectively. Therefore, molecularly targeted miRNA therapy could be a powerful tool to correct the cancer stem cell dysregulation.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A. 2003;100:9779–84.

    Article  PubMed  CAS  Google Scholar 

  2. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase II. Embo J. 2004;23:4051–60.

    Article  PubMed  CAS  Google Scholar 

  3. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. 2004;10:1957–66.

    Article  PubMed  CAS  Google Scholar 

  4. Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18:3016–27.

    Article  PubMed  CAS  Google Scholar 

  5. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17:3011–6.

    Article  PubMed  CAS  Google Scholar 

  6. Haase AD, Jaskiewicz L, Zhang H, Laine S, Sack R, Gatignol A, et al. TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing. EMBO Rep. 2005;6:961–7.

    Article  PubMed  CAS  Google Scholar 

  7. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436:740–4.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.

    Article  PubMed  CAS  Google Scholar 

  9. Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005;7:719–23.

    Article  PubMed  CAS  Google Scholar 

  10. Chekanova JA, Belostotsky DA. MicroRNAs and messenger RNA turnover. Methods Mol Biol. 2006;342:73–85.

    PubMed  CAS  Google Scholar 

  11. Croce CM, Calin GA. miRNAs, cancer, and stem cell division. Cell. 2005;122:6–7.

    Article  PubMed  CAS  Google Scholar 

  12. Rigoutsos I. New tricks for animal microRNAS: targeting of amino acid coding regions at conserved and nonconserved sites. Cancer Res. 2009;69:3245–8.

    Article  PubMed  CAS  Google Scholar 

  13. Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, et al. Human embryonic stem cells express a unique set of microRNAs. Dev Biol. 2004;270:488–98.

    Article  PubMed  CAS  Google Scholar 

  14. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, et al. Dicer is essential for mouse development. Nat Genet. 2003;35:215–7.

    Article  PubMed  CAS  Google Scholar 

  15. Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 2005;19:489–501.

    Article  PubMed  CAS  Google Scholar 

  16. Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H. Stem cell division is regulated by the microRNA pathway. Nature. 2005;435:974–8.

    Article  PubMed  Google Scholar 

  17. Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS. Stem cells in normal breast development and breast cancer. Cell Prolif. 2003;36(Suppl 1):59–72.

    Article  PubMed  CAS  Google Scholar 

  18. Farnie G, Clarke RB. Mammary stem cells and breast cancer—role of Notch signalling. Stem Cell Rev. 2007;3:169–75.

    Article  PubMed  CAS  Google Scholar 

  19. Papagiannakopoulos T, Kosik KS. MicroRNAs: regulators of oncogenesis and stemness. BMC Med. 2008;6:15.

    Article  PubMed  CAS  Google Scholar 

  20. Dick JE. Normal and leukemic human stem cells assayed in SCID mice. Semin Immunol. 1996;8:197–206.

    Article  PubMed  CAS  Google Scholar 

  21. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12:1167–74.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.

    Article  PubMed  CAS  Google Scholar 

  24. Lawson DA, Witte ON. Stem cells in prostate cancer initiation and progression. J Clin Invest. 2007;117:2044–50.

    Article  PubMed  CAS  Google Scholar 

  25. Tang DG, Patrawala L, Calhoun T, Bhatia B, Choy G, Schneider-Broussard R, et al. Prostate cancer stem/progenitor cells: identification, characterization, and implications. Mol Carcinog. 2007;46:1–14.

    Article  PubMed  CAS  Google Scholar 

  26. Patrawala L, Calhoun-Davis T, Schneider-Broussard R, Tang DG. Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44 + alpha2beta1+ cell population is enriched in tumor-initiating cells. Cancer Res. 2007;67:6796–805.

    Article  PubMed  CAS  Google Scholar 

  27. Li H, Chen X, Calhoun-Davis T, Claypool K, Tang DG. PC3 human prostate carcinoma cell holoclones contain self-renewing tumor-initiating cells. Cancer Res. 2008;68:1820–5.

    Article  PubMed  CAS  Google Scholar 

  28. Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res. 2004;6:R605–15.

    Article  PubMed  CAS  Google Scholar 

  29. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.

    Article  PubMed  CAS  Google Scholar 

  30. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A. 2007;104:973–8.

    Article  PubMed  CAS  Google Scholar 

  31. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.

    Article  PubMed  CAS  Google Scholar 

  32. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A. 2006;103:11154–9.

    Article  PubMed  CAS  Google Scholar 

  33. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.

    Article  PubMed  CAS  Google Scholar 

  34. Vescovi AL, Galli R, Reynolds BA. Brain tumour stem cells. Nat Rev Cancer. 2006;6:425–36.

    Article  PubMed  CAS  Google Scholar 

  35. Bussolati B, Grange C, Sapino A, Camussi G. Endothelial Cell Differentiation of Human Breast Tumor Stem/Progenitor Cells. J Cell Mol Med. 2009;13:309–19.

    Article  PubMed  CAS  Google Scholar 

  36. Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008;456:593–8.

    Article  PubMed  CAS  Google Scholar 

  37. Rich JN. Cancer stem cells in radiation resistance. Cancer Res. 2007;67:8980–4.

    Article  PubMed  CAS  Google Scholar 

  38. Al-Hajj M. Cancer stem cells and oncology therapeutics. Curr Opin Oncol. 2007;19:61–4.

    PubMed  Google Scholar 

  39. Wicha MS. Cancer stem cells and metastasis: lethal seeds. Clin Cancer Res. 2006;12:5606–7.

    Article  PubMed  Google Scholar 

  40. Morrison SJ, Spradling AC. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008;132:598–611.

    Article  PubMed  CAS  Google Scholar 

  41. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 2003;17:1253–70.

    Article  PubMed  CAS  Google Scholar 

  42. Zhang M, Behbod F, Atkinson RL, Landis MD, Kittrell F, Edwards D, et al. Identification of tumor-initiating cells in a p53-null mouse model of breast cancer. Cancer Res. 2008;68:4674–82.

    Article  PubMed  CAS  Google Scholar 

  43. Murat A, Migliavacca E, Gorlia T, Lambiv WL, Shay T, Hamou MF, et al. Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol. 2008;26:3015–24.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  45. Zencak D, Lingbeek M, Kostic C, Tekaya M, Tanger E, Hornfeld D, et al. Bmi1 loss produces an increase in astroglial cells and a decrease in neural stem cell population and proliferation. J Neurosci. 2005;25:5774–83.

    Article  PubMed  CAS  Google Scholar 

  46. Fasano CA, Dimos JT, Ivanova NB, Lowry N, Lemischka IR, Temple S. shRNA knockdown of Bmi-1 reveals a critical role for p21-Rb pathway in NSC self-renewal during development. Cell Stem Cell. 2007;1:87–99.

    Article  PubMed  CAS  Google Scholar 

  47. Hambardzumyan D, Becher OJ, Holland EC. Cancer stem cells and survival pathways. Cell Cycle. 2008;7:1371–8.

    PubMed  CAS  Google Scholar 

  48. Bhardwaj G, Murdoch B, Wu D, Baker DP, Williams KP, Chadwick K, et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol. 2001;2:172–80.

    Article  PubMed  CAS  Google Scholar 

  49. Zhang Y, Kalderon D. Hedgehog acts as a somatic stem cell factor in the Drosophila ovary. Nature. 2001;410:599–604.

    Article  PubMed  CAS  Google Scholar 

  50. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423:409–14.

    Article  PubMed  CAS  Google Scholar 

  51. Zhao RC, Zhu YS, Shi Y. New hope for cancer treatment: Exploring the distinction between normal adult stem cells and cancer stem cells. Pharmacol Ther. 2008;119:74–82.

    Article  PubMed  CAS  Google Scholar 

  52. Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, et al. Wnt/beta-catenin signaling pathway as a novel cancer drug target. Curr Cancer Drug Targets. 2004;4:653–71.

    Article  PubMed  CAS  Google Scholar 

  53. Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351:657–67.

    Article  PubMed  CAS  Google Scholar 

  54. Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer. 2007;7:899–910.

    Article  PubMed  CAS  Google Scholar 

  55. Abe N, Watanabe T, Suzuki Y, Matsumoto N, Masaki T, Mori T, et al. An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue. Br J Cancer. 2003;89:2104–9.

    Article  PubMed  CAS  Google Scholar 

  56. Meyer B, Loeschke S, Schultze A, Weigel T, Sandkamp M, Goldmann T, et al. HMGA2 overexpression in non-small cell lung cancer. Mol Carcinog. 2007;46:503–11.

    Article  PubMed  CAS  Google Scholar 

  57. Sparmann A, van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer. 2006;6:846–56.

    Article  PubMed  CAS  Google Scholar 

  58. Haupt Y, Alexander WS, Barri G, Klinken SP, Adams JM. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell. 1991;65:753–63.

    Article  PubMed  CAS  Google Scholar 

  59. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006;66:6063–71.

    Article  PubMed  CAS  Google Scholar 

  60. Domen J, Gandy KL, Weissman IL. Systemic overexpression of BCL-2 in the hematopoietic system protects transgenic mice from the consequences of lethal irradiation. Blood. 1998;91:2272–82.

    PubMed  CAS  Google Scholar 

  61. Domen J, Cheshier SH, Weissman IL. The role of apoptosis in the regulation of hematopoietic stem cells: Overexpression of Bcl-2 increases both their number and repopulation potential. J Exp Med. 2000;191:253–64.

    Article  PubMed  CAS  Google Scholar 

  62. Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS ONE. 2009;4:e6816.

    Article  PubMed  CAS  Google Scholar 

  63. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.

    Article  PubMed  CAS  Google Scholar 

  64. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci U S A. 2004;101:14228–33.

    Article  PubMed  CAS  Google Scholar 

  65. Wiemer EA. The role of microRNAs in cancer: no small matter. Eur J Cancer. 2007;43:1529–44.

    Article  PubMed  CAS  Google Scholar 

  66. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed Cell Death 4 (PDCD4) is an important functional target of the MicroRNA miR-21 in breast cancer cells. J Biol Chem. 2008;283:1026–33.

    Article  PubMed  CAS  Google Scholar 

  67. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27:2128–36.

    Article  PubMed  CAS  Google Scholar 

  68. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008;14:2348–60.

    Article  PubMed  CAS  Google Scholar 

  69. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene. 2007;26:2799–803.

    Article  PubMed  CAS  Google Scholar 

  70. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, et al. A polycistronic microRNA cluster, miR-17–92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005;65:9628–32.

    Article  PubMed  CAS  Google Scholar 

  71. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.

    Article  PubMed  CAS  Google Scholar 

  72. Lu Y, Thomson JM, Wong HY, Hammond SM, Hogan BL. Transgenic over-expression of the microRNA miR-17–92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol. 2007;310:442–53.

    Article  PubMed  CAS  Google Scholar 

  73. Uziel T, Karginov FV, Xie S, Parker JS, Wang YD, Gajjar A, et al. The miR-17 92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci U S A. 2009;106:2812–7.

    Article  PubMed  Google Scholar 

  74. Nagel R, le Sage C, Diosdado B, van der Waal M, Oude Vrielink JA, Bolijn A, et al. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res. 2008;68:5795–802.

    Article  PubMed  CAS  Google Scholar 

  75. Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007;67:7713–22.

    Article  PubMed  CAS  Google Scholar 

  76. Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A, Ford L, et al. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle. 2008;7:759–64.

    PubMed  CAS  Google Scholar 

  77. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005;120:635–47.

    Article  PubMed  CAS  Google Scholar 

  78. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131:1109–23.

    Article  PubMed  CAS  Google Scholar 

  79. Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007;315:1576–9.

    Article  PubMed  CAS  Google Scholar 

  80. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944–9.

    Article  PubMed  CAS  Google Scholar 

  81. Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, et al. The miR-15a-miR-16–1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14:1271–7.

    Article  PubMed  CAS  Google Scholar 

  82. Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G, et al. Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008;68:9125–30.

    Article  PubMed  CAS  Google Scholar 

  83. Garzia L, Andolfo I, Cusanelli E, Marino N, Petrosino G, De Martino D, et al. MicroRNA-199b–5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma. PLoS ONE. 2009;4:e4998.

    Article  PubMed  CAS  Google Scholar 

  84. Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M, et al. Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. Embo J. 2008;27:2616–27.

    Article  PubMed  CAS  Google Scholar 

  85. He X, He L, Hannon GJ. The guardian’s little helper: microRNAs in the p53 tumor suppressor network. Cancer Res. 2007;67:11099–101.

    Article  PubMed  CAS  Google Scholar 

  86. Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D, et al. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 2008;8:266.

    Article  PubMed  CAS  Google Scholar 

  87. Hatfield S, Ruohola-Baker H. microRNA and stem cell function. Cell Tissue Res. 2008;331:57–66.

    Article  PubMed  CAS  Google Scholar 

  88. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005;438:685–9.

    Article  PubMed  CAS  Google Scholar 

  89. Pirollo KF, Xu L, Chang EH. Non-viral gene delivery for p53. Curr Opin Mol Ther. 2000;2:168–75.

    PubMed  CAS  Google Scholar 

  90. Xu L, Pirollo KF, Chang EH. Tumor-targeted p53-gene therapy enhances the efficacy of conventional chemo/radiotherapy. J Control Release. 2001;74:115–28.

    Article  PubMed  CAS  Google Scholar 

  91. Xu L, Frederik P, Pirollo KF, Tang WH, Rait A, Xiang LM, et al. Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery. Hum Gene Ther. 2002;13:469–81.

    Article  PubMed  CAS  Google Scholar 

  92. Xu L, Huang CC, Huang W, Tang WH, Rait A, Yin YZ, et al. Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes. Molecular Cancer Therapeutics. 2002;1:337–46.

    PubMed  CAS  Google Scholar 

  93. Xu L, Pirollo KF, Tang WH, Rait A, Chang EH. Transferrin-liposome-mediated systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts. Hum Gene Ther. 1999;10:2941–52.

    Article  PubMed  CAS  Google Scholar 

  94. Xu L, Pirollo KF, Chang EH. Transferrin-liposome-mediated p53 sensitization of squamous cell carcinoma of the head and neck to radiation in vitro. Hum Gene Ther. 1997;8:467–75.

    Article  PubMed  CAS  Google Scholar 

  95. Xu L, Tang WH, Huang CC, Alexander W, Xiang LM, Pirollo KF, et al. Systemic p53 gene therapy of cancer with immunolipoplexes targeted by anti-transferrin receptor scFv. Mol Med. 2001;7:723–34.

    PubMed  CAS  Google Scholar 

  96. Pirollo KF, Rait A, Zhou Q, Hwang SH, Dagata JA, Zon G, et al. Materializing the potential of small interfering RNA via a tumor-targeting nanodelivery system. Cancer Res. 2007;67:2938–43.

    Article  PubMed  CAS  Google Scholar 

  97. Pirollo KF, Zon G, Rait A, Zhou Q, Yu W, Hogrefe R, et al. Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery. Hum Gene Ther. 2006;17:117–24.

    Article  PubMed  CAS  Google Scholar 

  98. Hogrefe RI, Lebedev AV, Zon G, Pirollo KF, Rait A, Zhou Q, et al. Chemically modified short interfering hybrids (siHYBRIDS): nanoimmunoliposome delivery in vitro and in vivo for RNAi of HER-2. Nucleosides Nucleotides Nucleic Acids. 2006;25:889–907.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We wish to thank Mr. Steven Kronenberg for graphical support and expertise in producing the figures. This review was supported in part by NIH grants CA121830, CA128220, and CA134655 (to L. X.). J. D. is a University of Michigan Undergraduate Research Opportunity Program (UROP) student.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Liang Xu.

Additional information

Guest Editor: Song Li

Rights and permissions

Reprints and permissions

About this article

Cite this article

DeSano, J.T., Xu, L. MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications. AAPS J 11, 682–692 (2009). https://doi.org/10.1208/s12248-009-9147-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12248-009-9147-7

Key words

Navigation