CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma—A miRNA microarray analysis

Guled, Mohamed; Lahti, Leo; Lindholm, Pamela; Salmenkivi, Kaisa; Bagwan, Izhar; Nicholson, Andrew G.; Knuutila, Sakari

doi:10.1002/gcc.20669

Cited by 250 publications

(198 citation statements)

References 43 publications

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“…The reduced miR-615-3p expression was then validated in the present study using 40 matched pairs of NSCLC and normal lung tissues, and the findings were consistent with the results reported in a previous study investigating malignant mesothelioma, which identified that miR-615-3p was downregulated in NSCLC tissues (14). Another study reported that miR-615-3p was upregulated and significantly associated with overall survival time in mantle-cell lymphoma (15).…”

Section: Discussionsupporting

confidence: 90%

Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer

Zhang

et al. 2017

Oncology Letters

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Abstract. Lung cancer is the most frequent cause of mortality in cancer patients; non-small-cell lung cancer (NSCLC) accounts for ~80% of lung cancer cases. MicroRNAs (miRNAs) have been revealed to perform an important role in cancer development and progression. Based on a custom miRNA microarray analysis of patients with NSCLC, miRNA-615-3p (miR-615-3p) downregulation was identified in NSCLC tissues compared with normal lung tissues, which suggested that miR-615-3p acted as a tumor suppressor in lung cancer. The overexpression of miR-615-3p was then validated using 40 pairs of NSCLC and adjacent normal tissue samples using a TaqMan reverse transcription-quantitative polymerase chain reaction assay. In order to investigate the tumor suppressor function of miR-615-3p, the ectopic expression of miR-615-3p in the NSCLC A549, H1299 and H1650 cell lines was established. The results revealed that overexpressed miR-615-3p markedly inhibited cell proliferation and colony formation in the 3 NSCLC cell lines compared with the cells overexpressing the negative control sequence (NC). Additional investigation revealed that miR-615-3p overexpression significantly induced apoptosis and cell cycle arrest at the G1 phase in the A549, H1299 and H1650 cell lines compared with the cells overexpressing NC. Finally, ectopic expression of miR-615-3p was found to repress the cell migration and invasion of the 3 lung cancer cell lines. The results of the present study demonstrate, for the first time, that miR-615-3p functions as a tumor suppressor in NSCLC, and may be a novel potential molecular therapeutic target for patients with NSCLC.

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Section: Discussionsupporting

confidence: 90%

Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer

Zhang

et al. 2017

Oncology Letters

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“…Human miR-483 is a microRNA located within intron 2 of the IGF2 locus. It has been found that mature miR-483-3p is overexpressed in malignant mesothelioma and Wilms' tumors [34,35]. In addition, the expression level of miR-483-3p is high or extremely high in many common adult human cancers, comprising 30% of cases of colon, breast and liver cancers [35].…”

Section: Discussionmentioning

confidence: 99%

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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“…Overexpression of the mature miRNA processed from the 3 0 arm of the stemloop miR-885 (miR-885-3p) has been previously reported in malignant mesothelioma tissues. 34 The relative underexpression of miR-885-5p in von Hippel-Lindau disease-related pheochromocytomas may be linked to the frequent loss of chromosome 3p25.3. Loss of 3p or that of whole chromosome 3 could be detected in 94% of von Hippel-Lindau disease pheochromocytomas.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas

et al. 2010

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MicroRNAs are involved in the pathogenesis of several tumors, however, there have been no data on microRNA expression in pheochromocytomas to date. The objective of our study was to perform microRNA expression profiling in sporadic and hereditary benign, and recurring adrenomedullary tumors. Furthermore, the applicability of formalin-fixed paraffin-embedded tissue samples for the analysis of microRNA expression in pheochromocytomas was examined. MicroRNA expression data of three matched frozen and formalin-fixed paraffin-embedded samples were correlated. A total of 21 formalin-fixed paraffin-embedded samples (sporadic benign, multiple endocrine neoplasia 2, von Hippel-Lindau disease, sporadic recurring) were subjected to microRNA expression profiling using microarrays. MicroRNAs with significant differences in expression were validated and sample sizes were extended including tumors from neurofibromatosis type 1 patients by real-time quantitative reverse-transcription PCR (n ¼ 33). MicroRNA target prediction was carried out by TargetScan and MicroCosm Targets. Pathway analysis of targets was performed by Ingenuity Pathway Analysis and DIANA mirPath. Furthermore, microRNA expression profiles of a malignant pheochromocytoma and a pair of primary and recurrent tumors were studied by TaqMan Human MicroRNA Cards. MicroRNA expression correlated well between frozen and formalin-fixed paraffinembedded samples (70-92%). Microarray analysis revealed 16 significantly differentially expressed microRNAs. Five of these were validated by real-time RT-PCR. miR-139-3p, miR-541 and miR-765 were significantly differentially expressed between sporadic benign and von Hippel-Lindau-related pheochromocytomas. Significantly higher expression of miR-885-5p and miR-1225-3p was found in multiple endocrine neoplasia type 2 and sporadic recurring pheochromocytomas, respectively. Pathway analysis revealed the possible involvement of Notch-and G-proteincoupled receptor signaling in tumor recurrence. MicroRNA expression profiles in the primary recurrent and recurring malignant comparisons have been similar. In conclusion, we have proved that formalin-fixed paraffinembedded samples can be used for the analysis of microRNA expression in pheochromocytomas. MicroRNA expression patterns differ between various sporadic, hereditary and recurring tumors and miR-1225-3p may be useful for identifying recurring pheochromocytomas.

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CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma—A miRNA microarray analysis

Cited by 250 publications

References 43 publications

Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer

Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer

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

MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas

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