MicroRNAs: Novel Diagnostic and Therapeutic Tools for Pancreatic Ductal Adenocarcinoma?

Mardin, Wolf Arif; Mees, Soeren Torge

doi:10.1245/s10434-009-0623-1

Cited by 49 publications

(30 citation statements)

References 45 publications

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“…The involvement of miRNAs in various human tumors suggests that they could also have regulatory functions in pancreatic cancer. Several miRNAs have been revealed as 'onco(genic)-miRs' or 'tumor-suppressor miRs' involved in pancreatic tumor development [17,18]. Yet, the molecular mechanisms of miRNAs in pancreatic cancer and their relationship with these regulatory factors are currently poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…And certain cancer histotypes can be classified based on miRNA expression profiles [14][15][16]. In pancreatic cancer, a multitude of misexpressed miRNAs have been reported, such as 'onco(genic)-miRs', miR-21 and miR-155, and 'tumor suppressor miRs', miR-29b and the miR-34 and let-7 families [17,18]. Moreover, it was recently found that miR-96 functions as a tumor-suppressor gene in pancreatic cancer by repressing KRAS expression [19].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer

et al. 2010

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a b s t r a c tBoth deregulation of tumor-suppressor genes and misexpression of microRNAs (miRNAs) have been implicated in the development of pancreatic cancer, but their relationship during this process remains less clear. Here, we report that the expression of miR-483-3p is strongly enhanced in pancreatic cancer tissues compared to side normal tissues using a miRNA-array differential analysis. Furthermore, DPC4/Smad4 is identified as a target of miR-483-3p and their expression levels are inversely correlated in human clinical specimens. Ectopic expression of miR-483-3p significantly represses DPC4/Smad4 protein levels in pancreatic cancer cell lines, and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-483-3p as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for the treatment of DPC4/ Smad4-driven pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer

et al. 2010

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“…5 These endogenous small noncoding RNA molecules of approximately 22 nucleotides display a critical role as epigenetic regulators of gene expression, acting posttranscriptionally through binding to their target messenger RNA (mRNA), resulting in translation inhibition. Microarray technology has revealed differential microRNA expression patterns depending on the tissue and cell type, and even on the developmental stages of a tumor.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer

Passadouro

Lima

Faneca

2014

IJN

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin–1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/−) (4/1) nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC.

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“…With profound understanding of the miRNA target genes and the cellular behaviors influenced by them, miRNA may become exciting targets for cancer therapy (Cho, 2010). Growing evidence suggests that aberrant miRNA expression contributes to the development and progression of PDAC (Bloomston et al, 2007;Szafranska et al, 2007;Mardin & Mees, 2009).…”

Section: Introductionmentioning

confidence: 99%