Cancer remains a worldwide epidemic. An improved understanding of the underlying molecular
mechanisms and development of effective targeted therapies are still required for
many deadly cancers. The discovery of microRNAs (miRNAs or miRs) nearly 20 years ago
introduced a new layer of complexity to gene regulation, but it also afforded us the
opportunity to further our understanding of the molecular pathogenesis of cancers.
Dysregulation of miRNAs is fundamental to the pathogenesis of many cancers based on
their involvement in basic cellular functions. In addition, these previously underrecognized,
noncoding RNAs have the capacity to target tens to hundreds of genes simultaneously.
Thus, they are attractive candidates as prognostic biomarkers and therapeutic targets
in cancer. However, several challenges remain in translating our current understanding
of miRNAs to clinical therapies. Herein, we provide a review of the current knowledge
of miRNAs in both solid and hematological malignancies with a focus on their potential
application as therapeutic targets in cancer.
Abbreviations:
AMO (Anti-miRNA oligonucleotides), CLL (chronic lymphocytic leukemia), DLEU (deleted in leukemia), EMT (epithelial mesenchymal transition), HCC (hepatocellular carcinoma), IGF-1 (insulin growth factor 1), IRS-1 (insulin receptor substrate 1), LNA (locked nucleic acid), MBL (monoclonal B-cell lymphocytosis), MDR (minimal deleted region), miRNA (microRNA), RISC (RNA-induced silencing complex), UTR (untranslated region)To read this article in full you will need to make a payment
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References
- The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell. 1993; 75: 843-854
- MicroRNAs: genomics, biogenesis, mechanism, and function.Cell. 2004; 116: 281-297
- Causes and consequences of microRNA dysregulation in cancer.Nat Rev Genet. 2009; 10: 704-714
- Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers.Proc Natl Acad Sci U S A. 2004; 101: 2999-3004
- MicroRNA biogenesis and cancer.Cancer Res. 2005; 65: 3509-3512
- MicroRNAs: fundamental facts and involvement in human diseases.Birth Defects Res C Embryo Today. 2006; 78: 180-189
- Microprocessor of microRNAs: regulation and potential for therapeutic intervention.Mol Cancer. 2010; 9: 134
- Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.Cancer Cell. 2006; 9: 435-443
- Modulation of microRNA processing by p53.Nature. 2009; 460: 529-533
- miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis.Nat Cell Biol. 2010; 12: 247-256
- Reduced expression of Dicer associated with poor prognosis in lung cancer patients.Cancer Sci. 2005; 96: 111-115
- Overexpression of Dicer in precursor lesions of lung adenocarcinoma.Cancer Res. 2007; 67: 2345-2350
- Impaired microRNA processing enhances cellular transformation and tumorigenesis.Nat Genet. 2007; 39: 673-677
- A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells.Cancer Cell. 2010; 18: 303-315
- Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival.Br J Cancer. 2010; 103: 1870-1874
- MicroRNAs and the hallmarks of cancer.Oncogene. 2006; 25: 6170-6175
- The hallmarks of cancer.Cell. 2000; 100: 57-70
- RAS is regulated by the let-7 microRNA family.Cell. 2005; 120: 635-647
- The let-7 microRNA represses cell proliferation pathways in human cells.Cancer Res. 2007; 67: 7713-7722
- Regression of murine lung tumors by the let-7 microRNA.Oncogene. 2010; 29: 1580-1587
- Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia.Proc Natl Acad Sci U S A. 2002; 99: 15524-15529
- miR-15 and miR-16 induce apoptosis by targeting BCL2.Proc Natl Acad Sci U S A. 2005; 102: 13944-13949
- MicroRNA-34a is an important component of PRIMA-1-induced apoptotic network in human lung cancer cells.Int J Cancer. 2010; 127: 313-320
- Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis.J Clin Invest. 2010; 120: 4141-4154
- P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis.Proc Natl Acad Sci U S A. 2010; 107: 6334-6339
- Implications of micro-RNA profiling for cancer diagnosis.Oncogene. 2006; 25: 6220-6227
- The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.Nat Cell Biol. 2008; 10: 593-601
- MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer.Genes Dev. 2009; 23: 2152-2165
- The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.Genes Dev. 2008; 22: 894-907
- A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells.EMBO Rep. 2008; 9: 582-589
- A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition.Cancer Res. 2008; 68: 7846-7854
- A microRNA targeting dicer for metastasis control.Cell. 2010; 141: 1195-1207
- Reprogramming of miRNA networks in cancer and leukemia.Genome Res. 2010; 20: 589-599
- Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.Cancer Cell. 2006; 9: 189-198
- MicroRNA signature predicts survival and relapse in lung cancer 4.Cancer Cell. 2008; 13: 48-57
- MicroRNA expression differentiates histology and predicts survival of lung cancer.Clin Cancer Res. 2010; 16: 430-441
- MicroRNA expression and clinical outcomes in patients treated with adjuvant chemotherapy after complete resection of non-small cell lung carcinoma.Cancer Res. 2010; 70: 8288-8298
- Modulation of K-Ras-dependent lung tumorigenesis by microRNA-21.Cancer Cell. 2010; 18: 282-293
- Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model.Nat Biotechnol. 2010; 28: 341-347
- miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells.Cell Death Differ. 2010; 17: 246-254
- A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer.PloS ONE. 2010; 5: e13735
- The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia.Cancer Cell. 2010; 17: 28-40
- A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.N Engl J Med. 2005; 353: 1793-1801
- MicroRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival.Blood. 2010; 116: 945-952
- MicroRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification.Blood. 2009; 113: 5237-5245
- MicroRNAs in the pathogeny of chronic lymphocytic leukaemia.Br J Haematol. 2007; 139: 709-716
- Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181.Cancer Res. 2006; 66: 11590-11593
- Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression.Proc Natl Acad Sci U S A. 2002; 99: 6955-6960
- CD5+CD23+ leukemic cell populations in TCL1 transgenic mice show significantly increased proliferation and Akt phosphorylation.Leukemia. 2010; 24: 970-975
- MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma.JAMA. 2008; 299: 425-436
- Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma.Clin Cancer Res. 2009; 15: 5878-5887
- Reduced accumulation of specific microRNAs in colorectal neoplasia.Mol Cancer Res. 2003; 1: 882-891
- MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells.FEBS J. 2009; 276: 6689-6700
- Modulation of mismatch repair and genomic stability by miR-155.Proc Natl Acad Sci U S A. 2010; 107: 6982-6987
- Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer.Dis Markers. 2009; 26: 27-34
- The role of microRNAs in liver cancer progression.Br J Cancer. 2010; 104: 235-240
- Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.Oncogene. 2009; 28: 3526-3536
- An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1alpha 3′ untranslated region confers risk for hepatocellular carcinoma.Carcinogenesis. 2009; 30: 2064-2069
- MicroRNA expression, survival, and response to interferon in liver cancer.N Engl J Med. 2009; 361: 1437-1447
- Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model.Cell. 2009; 137: 1005-1017
- Expression profiling identifies microRNA signature in pancreatic cancer.Int J Cancer. 2007; 120: 1046-1054
- Real-time expression profiling of microRNA precursors in human cancer cell lines.Nucleic Acids Res. 2005; 33: 5394-5403
- MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis.JAMA. 2007; 297: 1901-1908
- MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival.J Gastrointest Surg. 2008; 12: 2171-2176
- Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.Proc Natl Acad Sci U S A. 2008; 105: 7004-7009
- MicroRNA signatures in human ovarian cancer.Cancer Res. 2007; 67: 8699-8707
- Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: evidence supporting a mesothelial-to-epithelial transition.Gynecol Oncol. 2010; 116: 117-125
- A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer.Gynecol Oncol. 2009; 114: 457-464
- MicroRNA microarray identifies let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer.Cancer Res. 2008; 68: 10307-10314
- A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk.Cancer Res. 2010; 70: 6509-6515
- Targeting microRNAs in cancer: rationale, strategies and challenges.Nat Rev Drug Discov. 2010; 9: 775-789
- MicroRNA sponges: progress and possibilities.RNA. 2010; 16: 2043-2050
- A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis.Cell. 2009; 137: 1032-1046
- Emerging roles for natural microRNA sponges.Curr Biol. 2010; 20: R858-R861
- Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy.Mol Ther. 2010; 18: 1650-1656
- Efficient in vivo microRNA targeting of liver metastasis.Oncogene. 2010; ([Epub ahead of print])
- Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection.Science. 2010; 327: 198-201
- Resistance may not be futile: microRNA biomarkers for chemoresistance and potential therapeutics.Mol Cancer Ther. 2010; 9: 3126-3136
- Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1.J Biol Chem. 2008; 283: 33394-33405
- MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer.J Biol Chem. 2010; 285: 17869-17879
- MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity.Cancer Res. 2010; 70: 4528-4538
- MicroRNA 92a-2∗: a biomarker predictive for chemoresistance and prognostic for survival in patients with small cell lung cancer.J Thorac Oncol. 2010; 5: 1273-1278
- MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia.Mol Cancer. 2010; 9: 123
- Determination of genes and microRNAs involved in the resistance to fludarabine in vivo in chronic lymphocytic leukemia.Mol Cancer. 2010; 9: 115
- MicroRNAs modulate the chemosensitivity of tumor cells.Mol Cancer Ther. 2008; 7: 1-9
- MicroRNA expression profiles for the NCI-60 cancer cell panel.Mol Cancer Ther. 2007; 6: 1483-1491
- mRNA and microRNA expression profiles of the NCI-60 integrated with drug activities.Mol Cancer Ther. 2010; 9: 1080-1091
- A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis.Eur J Cancer. 2010; ([Epub ahead of print])
- Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer.J Clin Oncol. 2010; 28: 1721-1726
- The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform.Gynecol Oncol. 2009; 112: 55-59
- Circulating microRNAs as stable blood-based markers for cancer detection.Proc Natl Acad Sci U S A. 2008; 105: 10513-10518
- Detection of microRNA expression in human peripheral blood microvesicles.PLoS ONE. 2008; 3: e3694
- Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR).Methods. 2010; 50: 298-301
Article info
Publication history
Published online: February 07, 2011
Accepted:
January 19,
2011
Received in revised form:
January 19,
2011
Received:
December 2,
2010
Identification
Copyright
© 2011 Published by Elsevier Inc.
