MicroRNAs and cancer: From the bench to the clinicPotential Applications of MicroRNAs in Cancer Diagnosis, Prognosis, and Treatment
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)
MicroRNAs: genomics, biogenesis, mechanism, and function
Cell
(2004)MicroRNAs in vertebrate development
Curr Opin Genet. Dev
(2005)- et al.
The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia
Cancer Cell
(2010) In situ detection of precursor and mature microRNAs in paraffin embedded, formalin fixed tissues and cell preparations
Methods
(2008)- et al.
The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform
Gynecol Oncol
(2009) - et al.
MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia
Blood
(2008) - et al.
Unique microRNA molecular profiles in lung cancer diagnosis and prognosis
Cancer Cell
(2006) - et al.
RAS is regulated by the let-7 microRNA family
Cell
(2005) - et al.
EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines
Ann Oncol
(2008) - et al.
MicroRNA 29b functions in acute myeloid leukemia
Blood
(2009)
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
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
Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model
Cell
Specific activation of microRNAs-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells
Cancer Cell
Adeno-associated viral vectors and their redirection to cell-type specific receptors
Adv Genet
RNAi therapeutics: Principles, prospects and challenges
Adv Drug Deliv Rev
A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer
Gynecol Oncol
microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma
Blood
MicroRNAs and cell cycle regulation
Cell Cycle
Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis
Nucleic Acids Res
MicroRNAs and the failing heart
N Engl J Med
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
MicroRNAs in cancer
Annu Rev Med
MicroRNA expression profiles classify human cancers
Nature
A microRNA expression signature in human solid tumors defines cancer targets
Proc Natl Acad Sci USA
Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice
Proc Natl Acad Sci U S A
Targeting microRNAs in cancer: rationale, strategies and challenges
Nat Rev Drug Discov
Detection of microRNA expression in human peripheral blood microvesicles
PLoS One
Serum microRNAs are promising novel biomarkers
PLoS One
The microRNA spectrum in 12 body fluids
Clin Chem
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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.