MicroRNAs in Cancer

Reinhold Munker, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
George A Calin, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Published online: March 2011

DOI: 10.1002/9780470015902.a0023161

Initially considered an epiphenomenon, micro ribonucleic acids (also called miRNAs) and other small noncoding RNA molecules are now considered major players in cell biology. MiRNAs regulate gene expression through effects on translation, transcription and chromatin modification. Multiple miRNAs are dysregulated in human cancer and affect the proliferation and apoptosis, metastatic behaviour, invasiveness and phenotype of cancer cells. Virtually every cell type and cancer have a particular expression pattern of miRNA expression. This miRNA profile permits to classify cancer and often gives prognostic information. Profiling based on miRNAs may be more specific and robust than profiling based on mRNAs. MiRNAs can be studied in virtually all tissues including plasma. More work is necessary, but miRNAs have already improved our understanding of the pathogenesis of cancer and appear promising for diagnostic purposes as biomarkers and for the development of new genetic treatments.

Key Concepts:

  • MicroRNAs regulate gene expression.
  • MicroRNAs are important in the pathogenesis and progression of human cancer.
  • MicroRNAs can function as tumour suppressors and as tumour promoters (oncomirs).
  • MicroRNAs can serve as biomarkers for cancer and may become useful for the treatment of cancer.

Keywords: microRNAs; noncoding RNAs; gene profiling; cancer; leukaemia; malignancy

Figure 1. Biogenesis and functions of miRNAs (for details see text).
Figure 2. Methods used to study miRNAs (for details see Calin and Croce (2007) and Ferdin et al., 2010).
close
 References
    Balaguer F, Link A, Lozano JJ et al. (2010) Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis. Cancer Research 70: 6609–6618.
    Ballabio E, Mitchell T, van Kester MS et al. (2010) MicroRNA expression in Sézary syndrome: identification, function and diagnostic potential. Blood 116: 1105–1113.
    Blum W, Garzon R, Klisovic RB et al. (2010) Clinical response and miR-29b predictive significance in older AML patients treated with a-10 day schedule of decitabine. Proceedings of the National Academy of Sciences of the USA 107: 7473–7478.
    Calin GA and Croce CM (2007) Investigation of microRNA alterations in leukemias and lymphomas. Methods of Enzymology 427: 193–213.
    Calin GA and Croce CM (2009) Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes [review article]. Blood 114: 4761–4770.
    Calin GA, Dumitru C, Shimizu M et al. (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the USA 99: 15524–15529.
    Calin GA, Ferracin M, Cimmino A et al. (2005) MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. New England Journal of Medicine 353: 1793–1801.
    Calin GA, Sevignani C, Dumitru CD et al. (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences of the USA 101: 2999–3004.
    Christensen BC, Avissar-Whiting M, Ouellet LG et al. (2010) Mature microRNA sequence polymorphism in MIR196A2 is associated with risk and prognosis of head and neck cancer. Clinical Cancer Research 16: 3713–3720.
    Di Leva G, Gasparini P, Piovan C et al. (2010) MicroRNA cluster 221-222 and estrogen receptor interactions in breast cancer. Journal of National Cancer Institute 102: 706–721.
    Ferdin J, Kunej T and Calin GA (2010) Non-coding RNAs: Identification of cancer-associated microRNAs by gene profiling. Technology in Cancer Research and Treatment 9: 1–16.
    Garzon R, Heaphy CEA, Havelange V et al. (2009) MicroRNA29b functions in acute myeloid leukemia. Blood 114: 5331–5341.
    Garzon R, Volinia S, Liu CG et al. (2008) MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 111: 3183–3189.
    Heneghan HM, Miller N, Kelly R et al. (2010) Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist 15: 673–682.
    Incoronato M, Garofalo M, Urso L et al. (2010) miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED. Cancer Research 70: 3638–3646.
    Iorio MV, Casalini P, Piovan C et al. (2009) MicroRNA-205 regulates HER3 in human breast cancer. Cancer Research 69: 2195–2200.
    Iorio MV, Ferracin M, Liu CG et al. (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Research 65: 7065–7070.
    Ji J, Shi J, Budhu A et al. (2009) MicroRNA expression, survival, and response to interferon in liver cancer. New England Journal of Medicine 361: 1437–1447.
    Klein U, Lia M, Crespo M et al. (2010) The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell 17: 28–40.
    Kota J, Chivukula RR, O'Donnell KA et al. (2009) Therapeutic delivery of miR-26a inhibits cancer cell proliferation and induces tumor-specific apoptosis. Cell 137: 1005–1017.
    Krol J, Loedige I and Filipowicz W (2010) The widespread regulation of MicroRNA biogenesis, function and decay. Nature Reviews. Genetics 11: 597–610.
    Kulda V, Pesta M, Topolcan O et al. (2010) Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genetics and Cytogenetics 200: 154–160.
    Landi MT, Zhao Y, Rotunno M et al. (2010) MicroRNA expression differentiates histology and predicts survival of lung cancer. Clinical Cancer Research 16: 430–441.
    Lanford RE, Hildebrandt-Eriksen ES, Petri A et al. (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327: 198–201.
    Lebanony D, Benjamin H, Gilad S et al. (2009) Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma. Journal of Clinical Oncology 27: 2030–2037.
    Lewis BP, Burge CB and Bartel DP (2005) Conserved seed pairing often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120: 15–20.
    Li A, Omura N, Hong SM et al. (2010) Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. Cancer Research 70: 5226–5237.
    Li Y, Guessous F, Zhang Y et al. (2009) MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Research 69: 7569–7576.
    Liu X, Sempere LF, Ouyang H et al. (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. Journal of Clinical Investigation 120: 1298–1309.
    Lu J, Getz G, Miska EA et al. (2005) MicroRNA expression profiles classify human cancers. Nature 435: 834–838.
    Ma J, Dong C and Ji C (2010) MicroRNA and drug resistance. Cancer Gene Therapy 17: 523–531.
    Mitchell PS, Parkin RK, Kroh EM et al. (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the USA 105: 10513–10518.
    Navarro A, Diaz T, Martinez A et al. (2009) Regulation of JAK2 by miR-135a: prognostic impact in classic Hodgkin lymphoma. Blood 114: 2945–2951.
    Ng EKO, Chong WWS, Jin H et al. (2009) Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58: 1375–1381.
    Pichiorri F, Su SS, Ladetto M et al. (2008) MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proceedings of the National Academy of Sciences of the USA 105: 12885–12890.
    Pineau P, Volinia S, McJunkin K et al. (2010) miR-221 overexpression contributes to liver tumorigenesis. Proceedings of the National Academy of Sciences of the USA 107: 264–269.
    Roccaro AM, Sacco A, Thompson B et al. (2009) MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood 113: 6669–6680.
    Sarver AL, French AJ, Borralho PM et al. (2009) Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer 9: 401.
    Schetter AJ, Leung SY, Sohn JJ et al. (2008) MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299: 425–436.
    Sempere LF, Christensen M, Silahtaroglu A et al. (2007) Altered microRNA expression confined to specific epithelial cell subpopulation in breast cancer. Cancer Research 67: 11612–11620.
    Silva J, García V, Zaballos et al. (2010) Vesicle-related microRNAs in plasma of NSCLC patients and correlation with survival. European Respiratory Journal Express. E-pub (July 2010).
    Spizzo R, Nicoloso MS, Croce CM et al. (2009) SnapShot: microRNAs in cancer. Cell 137: 586e.
    Spizzo R, Nicoloso MS, Lupini L et al. (2010) miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor- in human breast cancer cells. Cell Death and Differentiation 17: 246–254.
    Starczynowski DT, Kuchenbauer F, Argiropoulos B et al. (2010) Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nature Medicine 16: 49–59.
    Volinia S, Calin GA, Liu CG et al. (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the USA 103: 2257–2261.
    Wiggins JF, Ruffino L, Kelnar K et al. (2010) Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Research 70: 5923–5930.
    Yamanaka Y, Tagawa H, Takahashi N et al. (2009) Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/ leukemia. Blood 114: 265–3275.
    Yanaihara N, Caplen N, Bowman E et al. (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9: 189–198.
    Zhao JJ, Lin J, Lwin T et al. (2010) microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood 115: 2630–2639.
    Zhou Y, Chen L, Barlogie B et al. (2010) High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proceedings of the National Academy of Sciences of the USA 107: 7904–7909.
 Further Reading
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136: 215–233.
    Dykxhoorn DM (2010) MicroRNAs and metastasis: little RNAs go a long way. Cancer Research 70: OF1–OF6.
    Lawrie CH (2007) MicroRNAs and haematology: small molecules, big function. British Journal of Haematology 137: 503–512.
    Ryan BM, Robles AI and Harris CC (2010) Genetic variations in microRNA networks: the implications for cancer research. Nature Reviews. Cancer 10: 389–402.

Related Sub-Topics:

Cell Biology of Cancer | Cancer Genetics | RNA Structure and Function | Noncoding RNA
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: MicroRNAs in Cancer
 
How to Cite close
Munker, Reinhold, and Calin, George A(Mar 2011) MicroRNAs in Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023161]