Elsevier

Seminars in Oncology

Volume 38, Issue 6, December 2011, Pages 781-787
Seminars in Oncology

MicroRNAs and cancer: From the bench to the clinic
Potential Applications of MicroRNAs in Cancer Diagnosis, Prognosis, and Treatment

https://doi.org/10.1053/j.seminoncol.2011.08.007Get rights and content

Early studies have established that microRNAs (miRNAs) are widely deregulated in cancer and play a critical role in cancer pathogenesis. Recent research efforts are directed now towards translating these basic discoveries into novel tests or treatments that could improve the diagnosis and outcome of cancer patients. In this review, we will summarize the potential applications of miRNAs for cancer diagnosis, prognosis, and treatment. In addition, we will discuss current pitfalls and future directions.

Section snippets

MicroRNAs in the Molecular Classification and Diagnosis of Cancer

The systematic profiling of miRNA expression in normal tissues uncovered the fact that most miRNAs are expressed in a tissue- and developmental stage-specific manner.1 Thus some miRNAs are enriched in a particular tissue or cell type (ie, miR-205 expression in squamous epithelium, or miR-375 in endocrine pancreas) and the pattern of miRNA expression varies according to the development or differentiation stage (ie, embryonic development).1, 7 The tissue specificity in miRNA expression is

Predicting Outcome Using miRNA Expression

Several studies have shown that miRNAs can predict outcome in cancer (see Table 1). In CLL a signature of nine miRNAs (including high levels of miR-155, miR-221, and miR-222 and low levels of miR-29c) was clearly associated with time to progression (Table 1).30 Our group reported that the overexpression of miR-191 and miR-199 in AML patients with intermediate and poor cytogenetic risk carries poor prognosis independent from other variables including cytogenetics (Table 1).31 In a second study

MicroRNA-Based Therapeutic Approaches for Cancer

Over the past years there has been a growing interest from academia and industry to pursue miRNA-based therapeutic approaches to fight cancer. The enthusiasm is justified by the following facts: (1) widespread miRNA deregulation in cancer; (2) few miRNAs (like miR-155, miR-21, miR-29) are deregulated in multiples cancers, and therefore developing compounds that target one of these miRNAs could potentially be used in many different tumors7, 9; and (3) a single miRNA can have many targets that

Conclusions

Recent data suggest that tumor and circulating miRNA expression could be potentially useful as biomarkers for cancer diagnosis, prognosis, and treatment response. It could help to identify the tissue of origin of poorly differentiated tumors, improve molecular classification, and detect cancer at earlier stages using noninvasive and highly sensitive and specific assays (Figure 1). Furthermore, there is a strong rationale to develop miRNA-based therapeutic strategies to fight cancer. There are

References (60)

  • R. Garzon et al.

    MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene re-expression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1

    Blood

    (2009)
  • S. Liu et al.

    Evidence of microRNA-29b and Sp1/NFκB-HDAC regulatory network for KIT expression in KIT-driven acute myeloid leukemia (AML): biologic and therapeutic implications

    Cancer Cell

    (2010)
  • J. Kota et al.

    Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model

    Cell

    (2009)
  • Y. Saito et al.

    Specific activation of microRNAs-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells

    Cancer Cell

    (2006)
  • S. Michelfelder et al.

    Adeno-associated viral vectors and their redirection to cell-type specific receptors

    Adv Genet

    (2009)
  • L. Aagaard et al.

    RNAi therapeutics: Principles, prospects and challenges

    Adv Drug Deliv Rev

    (2007)
  • X. Hu et al.

    A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer

    Gynecol Oncol

    (2009)
  • J.J. Zhao et al.

    microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma

    Blood

    (2010)
  • M. Carleton et al.

    MicroRNAs and cell cycle regulation

    Cell Cycle

    (2007)
  • A.M. Cheng et al.

    Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis

    Nucleic Acids Res

    (2005)
  • D.L. Mann

    MicroRNAs and the failing heart

    N Engl J Med

    (2007)
  • S.S. Hébert et al.

    Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression

    Proc Natl Acad Sci U S A

    (2008)
  • R. Garzon et al.

    MicroRNAs in cancer

    Annu Rev Med

    (2009)
  • J. Lu et al.

    MicroRNA expression profiles classify human cancers

    Nature

    (2005)
  • S. Volinia et al.

    A microRNA expression signature in human solid tumors defines cancer targets

    Proc Natl Acad Sci USA

    (2006)
  • S. Costinean et al.

    Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice

    Proc Natl Acad Sci U S A

    (2006)
  • R. Garzon et al.

    Targeting microRNAs in cancer: rationale, strategies and challenges

    Nat Rev Drug Discov

    (2010)
  • M. Piper-Hunter et al.

    Detection of microRNA expression in human peripheral blood microvesicles

    PLoS One

    (2008)
  • S. Gilad et al.

    Serum microRNAs are promising novel biomarkers

    PLoS One

    (2008)
  • J.A. Weber et al.

    The microRNA spectrum in 12 body fluids

    Clin Chem

    (2010)
  • Cited by (0)

    This work was supported in part by the National Institute of Health grants.

    The authors have no financial disclosures or conflicts of interest to declare.

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