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RETRACTED ARTICLE: Roles of MicroRNAs and Other Non-coding RNAs in Breast Cancer Metastasis

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

This article was retracted on 20 August 2016

Abstract

Despite the fact that metastases are responsible for the overwhelming majority of human cancer deaths, our comprehension of the molecular events that drive metastatic progression remains woefully incomplete. Excitingly, the recent appreciation that various species of non-coding RNAs—including microRNAs—play pivotal roles in dictating the malignant behaviors of breast carcinoma cells promises to afford new insights into the molecular circuitry that determines metastatic propensity. Here, I summarize our current knowledge regarding these still-emerging functions for non-coding RNAs in the pathogenesis of breast cancer metastasis, with an emphasis placed upon the roles played by microRNAs in these processes. Additionally, I discuss the potential translational opportunities afforded by these research findings for the diagnosis and treatment of human breast tumors. When assessed collectively, it is apparent that although this field of research is still in its infancy, comprehension of the biological actions of microRNAs and other non-coding RNAs will hold important consequences for our understanding of the etiology of metastatic disease, as well as its clinical management and treatment.

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Abbreviations

Bcl-2:

B-cell lymphoma-2

BM:

basement membrane

BMI1:

B lymphoma Mo-MLV insertion region-1

ceRNA:

competing endogenous RNA

CTC:

circulating tumor cell

ECM:

extracellular matrix

EGFR:

epidermal growth factor receptor

EMT:

epithelial-mesenchymal transition

HMGA2:

high mobility group AT-hook-2

HoxD10:

homeobox-D10

IGFBP2:

insulin-like growth factor binding protein-2

ITGA3:

integrin α3

ITGA5:

integrin α5

ITGA5:

integrin α5

ITGA5:

integrin α5

Klf4:

Kruppel-like factor-4

lincRNA:

long intergenic non-coding RNA

MERTK:

c-mer proto-oncogene tyrosine kinase

miRNA:

microRNA

MMP:

matrix metalloproteinase

ncRNA:

non-coding RNA

PDCD4:

programmed cell death-4

PITPNC1:

phosphatidylinositol transfer protein cytoplasmic-1

PRC2:

polycomb repressive complex-2

RDX:

radixin

rRNA:

ribosomal RNA

siRNA:

small interfering RNA

Sox4:

sex determining region Y-box-4

TFAP2C:

transcription factor AP-2 gamma

TIC:

tumor-initiating cell

TIMP3:

tissue inhibitor of metalloproteinases-3

tRNA:

transfer RNA

UCR:

unltraconserved region

UTR:

untranslated region

VEGFR:

vascular endothelial growth factor

ZEB:

zinc finger E-box binding homeobox

References

  1. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.

    Article  CAS  PubMed  Google Scholar 

  2. The American Cancer Society. “Cancer Facts and Figures 2009”. 2009. www.cancer.org.

  3. 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  CAS  PubMed  Google Scholar 

  4. Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214–21.

    Article  CAS  PubMed  Google Scholar 

  5. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.

    Article  CAS  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007;12:215–29.

    Article  CAS  PubMed  Google Scholar 

  8. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011;10:417–27.

    Article  CAS  PubMed  Google Scholar 

  9. 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 USA. 2005;102:13944–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Clevers H. The cancer stem cell: premises, promises and challenges. Nat Med. 2011;17:313–9.

    Article  CAS  PubMed  Google Scholar 

  11. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, et al. miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One. 2009;4:e7181.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Elmén J, Lindow M, Schütz S, Lawrence M, Petri A, Obad S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008;452:896–9.

    Article  PubMed  Google Scholar 

  13. Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.

    Article  CAS  PubMed  Google Scholar 

  14. Fang JH, Zhou HC, Zeng C, Yang J, Liu Y, Huang X, et al. MicroRNA-29b suppresses tumor angiogenesis, invasion, and metastasis by regulating matrix metalloproteinase 2 expression. Hepatology. 2011;54:1729–40.

    Article  CAS  PubMed  Google Scholar 

  15. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.

    Article  CAS  PubMed  Google Scholar 

  16. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, et al. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci USA. 2008;105:13021–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Friedl P, Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003;3:362–74.

    Article  CAS  PubMed  Google Scholar 

  18. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593–601.

    Article  CAS  PubMed  Google Scholar 

  19. Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nuc Acids Res. 2008; D154–158.

  20. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. He L, He X, Lowe SW, Hannon GJ. microRNAs join the p53 network–another piece in the tumour-suppression puzzle. Nat Rev Cancer. 2007;7:819–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 2008;10:202–10.

    Article  CAS  PubMed  Google Scholar 

  23. Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, et al. In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell. 2011;147:382–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kasinski AL, Slack FJ. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11:849–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celià-Terrassa T, et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011;17:1101–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5:115–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137:1005–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Krützfeldt 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  Google Scholar 

  29. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  CAS  PubMed  Google Scholar 

  30. Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 2008;105:13556–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, et al. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010;28:341–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.

    Article  CAS  PubMed  Google Scholar 

  33. Ma L, Young JJ, Prabhala H, Mestdagh P, Muth D, Teruya-Feldstein J, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biol. 2010;12:247–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, et al. A microRNA targeting Dicer for metastasis control. Cell. 2010;141:1195–207.

    Article  CAS  PubMed  Google Scholar 

  35. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8:329–40.

    Article  CAS  PubMed  Google Scholar 

  36. Penna E, Orso F, Cimino D, Tenaglia E, Lembo A, Quaglino E, et al. microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C. EMBO J. 2011;30:1990–2007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Png KJ, Halberg N, Yoshida M, Tavazoie SF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2011;481:190–4.

    Article  PubMed  Google Scholar 

  38. Prensner JM, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Cancer Discov. 2011;1:391–407.

    Article  CAS  PubMed  Google Scholar 

  39. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146:353–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, et al. Downregulation of miRNA-200c links breast cancer stem cells with mormal stem cells. Cell. 2009;138:592–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Song B, Wang C, Liu J, Wang X, Lv L, Wei L, et al. MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. J Exp Clin Cancer Res. 2010;29:29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sotiropoulou G, Pampalakis G, Lianidou E, Mourelatos Z. Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell. RNA. 2009;15:1443–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Takeshita F, Patrawala L, Osaki M, Takahashi RU, Yamamoto Y, Kosaka N, et al. Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes. Mol Ther. 2010;18:181–7.

    Article  CAS  PubMed  Google Scholar 

  44. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;45:147–52.

    Article  Google Scholar 

  45. Thiery JP, Acloque H, Huang RYJ, Neito MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.

    Article  CAS  PubMed  Google Scholar 

  46. Tili E, Croce CM, Michaille JJ. miR-155: on the crosstalk between inflammation and cancer. Int Rev Immunol. 2009;28:264–84.

    Article  CAS  PubMed  Google Scholar 

  47. Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene. 2010;29:1580–7.

    Article  CAS  PubMed  Google Scholar 

  48. Valastyan S, Benaich N, Chang A, Reinhardt F, Weinberg RA. Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis. Genes Dev. 2009;23:2592–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA. Activation of miR-31 function in already-established metastases elicits metastatic regression. Genes Dev. 2011;25:646–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137:1032–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Valastyan S, Weinberg RA. MicroRNAs: crucial multi-tasking components in the complex circuitry of tumor metastasis. Cell Cycle. 2009;8:3506–12.

    Article  CAS  PubMed  Google Scholar 

  52. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147:275–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ventura A, Jacks T. MicroRNAs and cancer: short RNAs go a long way. Cell. 2009;136:586–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ. Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J Biol Chem. 2009;284:5731–41.

    Article  CAS  PubMed  Google Scholar 

  55. 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;11:1487–95.

    Article  CAS  PubMed  Google Scholar 

  56. Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D, et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 2010;70:5923–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wu H, Zhu S, Mo YY. Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res. 2009;19:439–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 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  CAS  PubMed  Google Scholar 

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Acknowledgments

The author’s research is supported by the NIH, U.S. Department of Defense, and Damon Runyon Cancer Research Foundation. S.V. is the Harry Kriegel Fellow of the Damon Runyon Cancer Research Foundation. S.V. is an inventor on patent applications based in part on findings pertaining to miR-31 detailed in this manuscript.

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Authors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA, 02115, USA

    Scott Valastyan

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Correspondence to Scott Valastyan.

Additional information

This article, Roles of MicroRNAs and Other Non-coding RNAs in Breast Cancer Metastasis, by S. Valastyan, published in Journal of Mammary Gland Biology & Neoplasia, Volume 17, Issue 1, pages 23-32 (10.1007/s10911-012-9241-9), has been retracted at the request of the Editor-in-Chief because several studies referenced within the paper have subsequently been retracted due to data manipulation, which is a serious form of publishing misconduct.

An erratum to this article is available at http://dx.doi.org/10.1007/s10911-016-9360-9.

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Valastyan, S. RETRACTED ARTICLE: Roles of MicroRNAs and Other Non-coding RNAs in Breast Cancer Metastasis. J Mammary Gland Biol Neoplasia 17, 23–32 (2012). https://doi.org/10.1007/s10911-012-9241-9

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  • DOI: https://doi.org/10.1007/s10911-012-9241-9

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