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

Mairinger, Fabian; Ting, Saskia; Werner, Robert A.; Walter, Robert Fred Henry; Hager, Thomas; Vollbrecht, Claudia; Christoph, Daniel C.; Worm, Karl; Mairinger, Thomas; Sheu-Grabellus, Sien-Yi; Theegarten, Dirk; Schmid, Kurt Werner; Wohlschlaeger, Jeremias

doi:10.1038/modpathol.2014.74

Cited by 75 publications

(74 citation statements)

References 55 publications

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“…Different studies have examined miRNA expression in pulmonary carcinoids using different profiling platforms comparing normal lung tissue and tumour, carcinoids and high-grade NEC as well as localized and metastatic disease (Lee et al 2012, Deng et al 2014, Mairinger et al 2014, Rapa et al 2015. Although these studies are difficult to merge, some recurrent deregulated miRNAs in lung NET progression were identified, including miR-129-5p, miR-409-3p and miR-155.…”

Section: Pulmonary Carcinoidsmentioning

confidence: 99%

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Domenico

Wiedmer

Perren

2017

Endocrine-Related Cancer

111

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Neuroendocrine tumours (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumours. The molecular characterization and the clinical classification of these tumours have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole-exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well-differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging. Indeed, mutations in genes encoding for proteins directly involved in chromatin remodelling, such as DAXX and ATRX are a frequent event in NET. Epigenetic changes are reversible and targetable; therefore, an attractive target for treatment. The discovery of the mechanisms underlying the epigenetic changes and the implication on gene and miRNA expression in the different subgroups of NET may represent a crucial change in the diagnosis of this disease, reveal new therapy targets and identify predictive markers. Molecular profiles derived from omics data including DNA mutation, methylation, gene and miRNA expression have already shown promising results in distinguishing clinically and molecularly different subtypes of NET. In this review, we recapitulate the major genetic and epigenetic characteristics of pancreatic, lung and small intestinal NET and the affected pathways. We also discuss potential epigenetic mechanisms leading to NET development.

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Section: Pulmonary Carcinoidsmentioning

confidence: 99%

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Domenico

Wiedmer

Perren

2017

Endocrine-Related Cancer

111

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“…In the study by Lee et al [14], the expression levels of miR-21 and miR-155 were much higher in high-grade carcinomas than in carcinoids, and in the latter group, they were more frequently associated with carcinoids with lymph node metastases but were not helpful in distinguishing typical from atypical carcinoids. In contrast, in a very recent study, Mairinger et al [15] applied a microRNA profiling approach to a limited series of cases but without carcinoid-specific clinical or pathological correlations nor a validation cohort.…”

Section: Introductionmentioning

confidence: 99%

“…In the lung, a study reported the validation of a microRNA-based assay developed to differentiate between the 4 main types of lung cancer, i.e., adenocarcinoma, squamous-cell carcinoma, carcinoids and small-cell carcinoma [13]. Apart from that, 2 other studies dedicated to lung neuroendocrine tumors are on record encompassing the whole spectrum of histological types (from carcinoids to high-grade neuroendocrine carcinomas) [14,15]. In the study by Lee et al [14], the expression levels of miR-21 and miR-155 were much higher in high-grade carcinomas than in carcinoids, and in the latter group, they were more frequently associated with carcinoids with lymph node metastases but were not helpful in distinguishing typical from atypical carcinoids.…”

Section: Introductionmentioning

confidence: 99%

Identification of MicroRNAs Differentially Expressed in Lung Carcinoid Subtypes and Progression

et al. 2015

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Aim: To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features. Methods: A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 atypical (3 with lymph node metastasis). The results were validated by means of real-time PCR in 37 carcinoids, including 22 typical (4 with lymph node metastasis) and 15 atypical (7 with lymph node metastasis), and 19 high-grade neuroendocrine carcinomas. Results: Unsupervised cluster analysis segregated the pilot cases into 3 distinct groups. Twenty-four microRNAs were differentially regulated in atypical versus typical carcinoids, and 29 in metastatic versus nonmetastatic cases. Eleven microRNAs were selected for validation. All but 1 were significantly different among lung neuroendocrine tumor histotypes. Moreover, 5 (miR-129-5p, miR-409-3p, miR-409-5p, miR-185 and miR-497) were significantly upregulated in typical compared to atypical carcinoids. MiR-409-3p, miR-409-5p and miR-431-5p were also significantly downregulated in carcinoids metastatic to the lymph nodes. Predictive in silico analysis of specific target genes showed that these 3 latter microRNAs linked to metastatic potential are implicated in several cellular functions and highlighted several novel genes which may be worth exploring. Conclusions: Our findings demonstrate that lung carcinoids have distinct microRNA expression profiles as compared to high-grade neuroendocrine carcinomas and that specific microRNAs might have potential implications as diagnostic tools or clinical biomarkers.

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“…Over expression of miR18a enhanced the colony-forming capacity of mouse bone marrow progenitor cells and it targets Smad2 and Smad4 in TGF-β signaling pathways [40]. Previous studies have shown that miR-18a was over expressed [42] and also down regulation of miR-18a sensitizes lung cancer cells to radiation treatment [43]. They are highly elevated to promote cancer through directly targeting STK4 gene and suppress apoptosis process [44].…”

Section: Discussionmentioning

confidence: 99%

Untitled

2017

RJLBPCS

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ABSTRACT:The complex history of consensus sequence in microRNA family appears to be closely linked to the early evolution of primates. Each miRNA is predicted to target several hundred genes and the expression pattern of conserved miRNA among species through evolutionary time is an important phenomenon in cancer.Since miRNAs are major post-transcriptional negative regulators of target gene transcript; their origins and functional evolution in primates still remains unclear and controversial. Sixteen miRNAs from seven different types of cancers were analyzed to identify the conserved miRNAs in human and to assess their expression patterns. Evolutionarily conserved sequences were identified among primates for 16 miRNAs by ClustalV algorithm. The expression patterns of 16 miRNAs were confirmed by RT-qPCR. The consensus sequence match was observed in cancer with GU-rich region among globally expressed miRNAs. However, there was an AU-rich region was observed in all sixteen matured miRNAs. Moreover, GU-rich region was observed in stem-loop structured miRNAs. This result indicated that CU-region does not or less evolutionary conserved in cancer and it was replaced by other regions during evolution. The result reveals that these 16 miRNAs showed similar sequence conservation among primates and differentially expressed in seven different types of human cancer cell lines. The present research work reports the sequence conservation of globally expressed miRNA through evolution among primates located on the top branch of the phylogenetic tree and the conserved miRNAs are the major regulators in cancer.

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

Cited by 75 publications

References 55 publications

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Identification of MicroRNAs Differentially Expressed in Lung Carcinoid Subtypes and Progression

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