MicroRNAs in Cancer: Small Molecules With a Huge Impact

Iorio, Marilena V.; Croce, Carlo M.

doi:10.1200/jco.2009.24.0317

Cited by 880 publications

(722 citation statements)

References 103 publications

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“…[15][16][17][18][19] In pancreatic adenocarcinomas, the expression of miR-15b, miR-21, miR-95, miR-103, miR-107, miR-148a, miR-155, miR-196a, miR-200, miR-210, miR-217, miR-221, miR-222 and miR-375 are different from tissue of normal pancreas and chronic pancreatitis. 17,[20][21][22][23][24][25][26][27] The results reported by Bloomston et al 20 and Szafranska et al 26 give promises of significant clinical impact of microRNA expression profiles to separate tissue from pancreatic adenocarcinomas from normal pancreas and chronic pancreatitis. The study by Szafranska et al 26 included a combination of two microRNAs (the difference between miR-196a and miR-217) to separate pancreatic adenocarcinomas and chronic pancreatitis (ASURAGEN-test).…”

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confidence: 97%

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Schultz

Werner

Willenbrock³

et al. 2012

Modern Pathology

132

106

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MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b* and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P ¼ 2.06 Â 10 À 54 ) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from nonneoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer. Modern Pathology (2012Pathology ( ) 25, 1609Pathology ( -1622 doi:10.1038/modpathol.2012; published online 10 August 2012Keywords: ampullary adenocarcinoma; chronic pancreatitis; microRNA; normal pancreas; pancreatic adenocarcinoma; pancreatic cancer Pancreatic cancer is the fourth most common cause of cancer death in United States and Europe. 1,2 Less than 20% of the patients can be operated with curative intent and the 5-year survival after surgery is below 20%. 3 Early diagnosis is difficult and the clinical and histological similarities between pancreatic cancer and chronic pancreatitis further complicate the differentiation between inflammation and cancer.

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confidence: 97%

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Schultz

Werner

Willenbrock³

et al. 2012

Modern Pathology

132

106

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“…2,3,12,13 Therefore, miRNAs are involved in a wide range of biological functions, including cellular proliferation, differentiation, angiogenesis, apoptosis, and metastatic potential. 2,[12][13][14][15][16][17] Aberrant miRNA expression has been reported to be involved in the pathogenesis of Alzheimer's disease, 18 cardiovascular disease, 19 spinal motor neuron anomalies, 20 and numerous others. 2 Furthermore, deregulated expression of miRNAs has been identified in a variety of human malignancies, 12,13,[21][22][23][24][25][26][27][28][29] suggesting that miRNAs function as potential oncogenic factors or tumor suppressors, depending on the cell type or tissue investigated and their target genes.…”

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confidence: 99%

Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: results of a profiling study

et al. 2014

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“…Introduction microRNA (miRNA) expression is deregulated in many human cancers (Calin and Croce, 2006;Iorio and Croce, 2009). In most cases, miRNAs binding to the 3 0 -untranslated regions (3 0 -UTR) of the targeted mRNA leads to degradation or translational repression (Bartel, 2004).…”

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confidence: 99%

miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1

et al. 2011

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MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from the CD44 þ /CD24 À/low sub-population, we have isolated a novel PROCR þ /ESA þ BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR þ /ESA þ cells. Coincidently, high upregulation of miR-495 was also found in CD44 þ /CD24 À/low BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through posttranscriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.

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MicroRNAs in Cancer: Small Molecules With a Huge Impact

Cited by 880 publications

References 103 publications

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: results of a profiling study

miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1

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