Contribution of microRNA analysis to characterisation of pancreatic lesions: a review

Visani, Michela; Acquaviva, Giorgia; Fiorino, Sirio; Reggiani, Maria Letizia Bacchi; Masetti, Michele; Franceschi, Enrico; Fornelli, Adele; Jovine, Elio; Fabbri, Carlo; Brandes, Alba Ariela; Tallini, Giovanni; Pession, Annalisa; Biase, Dario de

doi:10.1136/jclinpath-2015-203246

Cited by 16 publications

(17 citation statements)

References 99 publications

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“…In cyst fluid samples, miR-21 and miR-221 were significantly over-expressed in malignant cysts when compared with benign or premalignant [29]. Other miRNAs have been shown to be upregulated or downregulated in plasma, serum, stool and fluids of patients with pancreatic cancer [30,31]. Because these findings are consistent with those reported in pancreatic tissue, the less invasive procedures could be used for early diagnosis especially in patients at high risk to develop PDAC.…”

Section: Mirna and Pancreatic Diseases: Diagnosis Prognosis And Thersupporting

confidence: 71%

“…Therapeutic applications for miRNAs consist of two strategies: (1) miRNA replacement therapy against loss of function or (2) anti-miRNA therapy against gain of function [20,31,35]. The replacement therapy has the potential to replace malfunctioning tumor suppressor miRNAs and overcome carcinogenesis by reestablishing their normal levels.…”

Section: Mirna and Pancreatic Diseases: Diagnosis Prognosis And Thermentioning

confidence: 99%

“…The replacement therapy has the potential to replace malfunctioning tumor suppressor miRNAs and overcome carcinogenesis by reestablishing their normal levels. miRNAs Let-7, miR-34a, miR-96, miR-375 and the miR-200 family are the most promising candidates as tumor-suppressive miRNAs [31,35]. When downregulated, miRNA Let-7 is responsible for renewal and metastasis of pancreatic cancer cells.…”

Section: Mirna and Pancreatic Diseases: Diagnosis Prognosis And Thermentioning

confidence: 99%

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miRNA analysis in pancreatic cancer: the Dartmouth experience

Abreu

Tsongalis

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Pancreatic cancer is considered one of the most lethal cancers being the fourth leading cause of cancer deaths in adults in the United States because of the lack of early signs and symptoms and the lack of early detection. Pancreatic ductal adenocarcinoma (PDAC) is the most common histological type among pancreatic cancers, representing 80%-90% of all solid tumors of the pancreas. The majority of PDAC develops from three precursor lesions: pancreatic intraepithelial neoplasia, intraductual papillary mucinous neoplasm and mucinous cystic neoplasm.

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Section: Mirna and Pancreatic Diseases: Diagnosis Prognosis And Thersupporting

confidence: 71%

Section: Mirna and Pancreatic Diseases: Diagnosis Prognosis And Thermentioning

confidence: 99%

Section: Mirna and Pancreatic Diseases: Diagnosis Prognosis And Thermentioning

confidence: 99%

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miRNA analysis in pancreatic cancer: the Dartmouth experience

Abreu

Tsongalis

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…The findings of intermediate miR-216/-217 expression in the old P48 +/Cre ;LSL-KRAS G12D mice are not surprising due to the mosaic expression of Kras in these mice. A recent review of the differential miRNA expression in human PDAC tissues compiled an 18 miRNA signature of PDAC from the differentially expressed miRNAs (13 increased and 5 decreased) reported in at least three studies (Visani et al 2015). Our data from miRNA expression profiling in the KRAS G12D transgenic mouse model of PDAC report that 8 of the 18 miRNAs in the human signature were also differentially expressed in the mouse model of PDAC (5 increased and 3 decreased).…”

Section: Resultsmentioning

confidence: 99%

“…Numerous profiling studies over the past decade have shown that the expression miRNAs are altered in cancer, including pancreatic (Bloomston et al 2007, Lee et al 2007, Szafranska et al 2007, Volinia et al 2006). miRNAs reported as deregulated in human PDAC include overexpressed miRNAs (miR-21, miR-155, miR-181a/b, and miR-221/-222) and those with reduced expression in the tumor (miR-217, miR-216a/b, miR-375, and miR-148a) recently reviewed in Visani et al (2015). It was further noted that overexpression of certain miRNAs (i.e., miR-155 or miR-21) (Costinean et al 2006, Medina, Nolde, and Slack 2010) or knockout of other miRNAs such as miR-122 in the liver can contribute to the development of cancer in mice (Hsu et al 2012, Tsai et al 2012).…”

Section: Introductionmentioning

confidence: 99%

miR-216 and miR-217 expression is reduced in transgenic mouse models of pancreatic adenocarcinoma, knockout of miR-216/miR-217 host gene is embryonic lethal

Azevedo-Pouly

Sutaria

Jiang

et al. 2016

Funct Integr Genomics

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Mice harboring a G12D activating Kras mutation are among the most heavily studied models in the field of pancreatic adenocarcinoma (PDAC) research. miRNAs are differentially expressed in PDAC from patients and mouse models of PDAC. To better understand the relationship that Kras activation has on miRNA expression, we profiled the expression of 629 miRNAs in RNA isolated from the pancreas of control, young, and old P48+/Cre;LSL-KRASG12D as well as PDX-1-Cre;LSL-KRASG12D mice. One hundred of the differentially expressed miRNAs had increased expression in the advanced disease (old) P48+/Cre;LSL-KRASG12D compared to wild-type mice. Interestingly, the expression of three miRNAs, miR-216a, miR-216b, and miR-217, located within a ~30-kbp region on 11qA3.3, decreased with age (and phenotype severity) in these mice. miR-216/-217 expression was also evaluated in another acinar-specific ELa-KrasG12D mouse model and was downregulated as well. As miR-216/-217 are acinar enriched, reduced in human PDAC and target KRAS, we hypothesized that they may maintain acinar differentiation or represent tumor suppressive miRNAs. To test this hypothesis, we deleted a 27.9-kbp region of 11qA3.3 containing the miR-216/-217 host gene in the mouse's germ line. We report that germ line deletion of this cluster is embryonic lethal in the mouse. We estimate that lethality occurs shortly after E9.5. qPCR analysis of the miR-216b and miR-217 expression in the heterozygous animals showed no difference in expression, suggesting haplosufficiency by some type of compensatory mechanism. We present the differential miRNA expression in KrasG12D transgenic mice and report lethality from deletion of the miR-216/-217 host gene in the mouse's germ line.

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Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Duell

Luján-Barroso

Sala

et al. 2017

Intl Journal of Cancer

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Non-invasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate pre-diagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155, and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status, and age/date/time of blood collection. MiR levels in pre-diagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates, and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 yr of blood collection compared to matched controls (all P-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155, and -212) overall, and for four miRs (-10a, -10b, -21-5p, and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (P-value=0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-p).

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Contribution of microRNA analysis to characterisation of pancreatic lesions: a review

Abstract: Pancreatic tumours are usually very aggressive cancer with a poor prognosis.

Cited by 16 publications

References 99 publications

miRNA analysis in pancreatic cancer: the Dartmouth experience

miRNA analysis in pancreatic cancer: the Dartmouth experience

miR-216 and miR-217 expression is reduced in transgenic mouse models of pancreatic adenocarcinoma, knockout of miR-216/miR-217 host gene is embryonic lethal

Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

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