Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma

Cioce, Mario; Ganci, Federica; Canu, Valeria; Sacconi, Andrea; Mori, Federica; Canino, Claudia; Korita, Etleva; Casini, Beatrice; Alessandrini, Gabriele; Cambria, A; Carosi, Maria Antonia; Blandino, R.; Panebianco, Vincenzo; Facciolo, Francesco; Visca, P.; Volinia, Stefano; Muti, Paola; Strano, Sabrina; Croce, Carlo M.; Pass, Harvey I.; Blandino, Giovanni

doi:10.1038/onc.2013.476

Cited by 72 publications

(87 citation statements)

References 56 publications

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“…miRNAs, which usually induce gene silencing, can function as either tumor suppressors or oncogenes (17). Recent studies have identified several miRNAs with diagnostic, prognostic and therapeutic potential in pulmonary malignant diseases including NSCLC and MPM (18)(19)(20)(21). For example, the identification of low levels of miR-29c in MPM has provided both a new prognostic tool and has pointed to aberrant chromatin methylation as being involved in progression of the disease (20).…”

Section: Introductionmentioning

confidence: 97%

“…For example, the identification of low levels of miR-29c in MPM has provided both a new prognostic tool and has pointed to aberrant chromatin methylation as being involved in progression of the disease (20). A recent study demonstrated that loss of miR-145 affects tumorigenic properties of MPM cell lines (21). These findings have prompted the study of miRNA expression levels as potentially important diagnostic and prognostic tools in MPM.…”

Section: Introductionmentioning

confidence: 98%

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miR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma

et al. 2014

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Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence in Japan. In this study, we performed gene and microRNA (miRNA) expression profiling to identify novel therapeutic targets in MPM cells. Based on relative sensitivities to pemetrexed (PEM) and the histone deacetylase (HDAC) inhibitor, vorinostat (SAHA), 211H cells were determined to be the only sensitive MPM cell line out of the 6 tested. On the same series of cell lines, we performed whole genome transcriptomic profiling via DNA microarrays and pathway analysis of the derived data. Of particular note, IL-18 gene expression levels were significantly higher in the cell lines that were either drug resistant or displayed intermediate sensitivity, compared to the sensitive 211H cell line. Pathway analysis revealed IL-18 as an important gene associated with drug sensitivity of MPM cells. A relationship between IL-18 overexpression and drug resistance was also observed following targeted assessment of 10 cytokine genes using quantitative RT-PCR. miRNA expression profiles were evaluated in the MPM cell line panel in order to discern the mechanism of IL-18 induction in the drug-resistant lines. We found that miR-379 and miR-411 belonged to the same cluster of miRNAs located on chromosome 14q32 that commonly target the IL-18 gene. Luciferase reporter assays revealed that miR-379 and miR-411 directly target the IL-18 gene. Introduction of miR-379 plus miR-411, as well as IL-18 silencing, significantly suppressed the invasive capacity of MESO1 cells in vitro. Furthermore, the use of either PEM or SAHA together with miR-379 plus miR-411 mimics mediated increased sensitivity to these drugs in MESO1 cells. These results suggest that the miR-379/411 cluster may provide new therapeutic opportunities for advanced MPM patients, depending on the nature of IL-18 gene expression.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

miR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma

et al. 2014

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“…3 Emerging evidence has shown that miRNAs are involved in cancer initiation and progression. 4 MiR-145 has been reported as an important tumor suppressor gene in ovarian carcinoma, 5,6,7 malignant pleural mesothelioma, 8 breast cancer, 9 pancreatic cancer, 10,11 liposarcoma, 12 colorectal cancer, 13,14,15,16 neuroblastoma, 17 breast cancer, 18,19,20,21 esophageal cancer, 22 bladder cancer, 23,24 urothelial cancer, 25 prostate cancer, 26,27 gastric cancer, 28 and head and neck cancer, 29 and other types. MiR-145 was also implicated in the progression of NSCLC; 30,31,32 however, its exact mechanism is not well established.…”

Section: Introductionmentioning

confidence: 99%

Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1

Shen

Weng

et al. 2015

Cancer Biology & Therapy

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“…miR145-5p has been shown to act as a tumor suppressor in different tumor types (36). Its downregulation was associated with neoplastic cell growth, invasion, and metastasis and is paired with increased expression of different oncogenic mRNA targets expression, such as EGFR, MYC, MUC1, OCT4, and RTKN (8,36,43).…”

Section: Discussionmentioning

confidence: 99%

“…4,5). There is a growing consensus that miRNA downregulation has a profound impact on the genesis of tumors (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of microRNAs 145-3p and 145-5p Is a Long-term Predictor of Postmenopausal Breast Cancer Risk: The ORDET Prospective Study

Muti

Sacconi²,

Hossain

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: miRNAs have been implicated in the regulation of key metabolic, inflammatory, and malignant pathways; hence, they might be considered both predictors and players of cancer development.Methods: Using a case-control study design nested in the ORDET prospective cohort study, we addressed the possibility that specific mRNAs can serve as early predictors of breast cancer incidence in postmenopausal women. We compared leukocyte miRNA profiles of 133 incident postmenopausal breast cancer cases and profiles of 133 women who remained healthy over a follow-up period of 20 years.Results: The analysis identified 20 differentially expressed miRNAs, 15 of which were downregulated. Of the 20 miRNAs, miR145-5p and miR145-3p, each derived from another arm of the respective pre-miRNA, were consistently and significantly downregulated in all the databases that we surveyed. For example, analysis of more than 1,500 patients (the UK Metabric cohort) indicated that high abundance of miR145-3p and miR145-5p was associated with longer, and for miR145-3p also statistically significant, survival. The experimental data attributed different roles to the identified miRNAs: Although the 5p isoform was associated with invasion and metastasis, the other isoform seems related to cell proliferation.Conclusions: These observations and the prospective design of our study lend support to the hypothesis that downregulation of specific miRNAs constitutes an early event in cancer development. This finding might be used for breast cancer prevention.Impact: The identification of the miRNAs as long-term biomarkers of breast cancer may have an impact on breast cancer prevention and early detection. Cancer Epidemiol Biomarkers Prev; 23(11); 2471-81. Ó2014 AACR.

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Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma

Cited by 72 publications

References 56 publications

miR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma

miR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma

Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1

Downregulation of microRNAs 145-3p and 145-5p Is a Long-term Predictor of Postmenopausal Breast Cancer Risk: The ORDET Prospective Study

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