Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer

Valcárcel-Jiménez, Lorea; Macchia, Alice; Martín-Martín, Natalia; Cortazar, Ana R.; Schaub-Clerigué, Ariane; Pujana-Vaquerizo, Mikel; Fernández-Ruiz, Sonia; Lacasa-Viscasillas, Isabel; Santos-Martin, Aida; Loizaga-Iriarte, Ana; Unda, Miguel; Heřmanová, Ivana; Astobiza, Ianire; Graupera, Mariona; Starková, Júlia; Sutherland, James D.; Barrio, Rosa; Aransay, Ana M.; Carracedo, Arkaitz; Torrano, Verónica

doi:10.1038/s41419-018-1096-6

Cited by 15 publications

(13 citation statements)

References 66 publications

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“…Additional personalized cutoffs can be established through the access to raw data files provided in the custom analysis. Indeed, the inverse association of MITF to disease-free survival was significant in two out of three datasets analyzed when the patients within the first quartile of gene expression were compared with the rest of the cohort (18). Of note, in support of the possibility of monitoring the expression of LINCs in CANCERTOOL, Supplementary Fig.…”

Section: Basic Analysesmentioning

confidence: 76%

“…1, we depict an illuminating example of the analysis of a gene identified as potential regulator of prostate cancer biology using this type of Basic Analyses tool. This gene was subsequently corroborated as an important player in this tumor type (18). The Representative heatmap provided by CANCERTOOL for the correlation analyses of MITF against the indicated genes in multiple prostate cancer datasets.…”

Section: Basic Analysesmentioning

confidence: 97%

“…Coherence estimates consistent correlations when more than 50% of the datasets show a significant and unidirectional correlation with correlation coefficient greater than 0.2 (for direct correlations) or lower than À0.2 (for inverse correlations; Supplementary Table S2). The Correlations section in CANCERTOOL can aid the researcher in the screening and selection of the best potential gene associations to uncover functional implications in cancer (18).…”

Section: Correlationsmentioning

confidence: 99%

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CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

et al. 2018

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With the advent of OMICs technologies, both individual research groups and consortia have spear-headed the characterization of human samples of multiple pathophysiologic origins, resulting in thousands of archived genomes and transcriptomes. Although a variety of web tools are now available to extract information from OMICs data, their utility has been limited by the capacity of nonbioinformatician researchers to exploit the information. To address this problem, we have developed CANCERTOOL, a web-based interface that aims to overcome the major limitations of public transcriptomics dataset analysis for highly prevalent types of cancer (breast, prostate, lung, and colorectal). CANCERTOOL provides rapid and comprehensive visualization of gene expression data for the gene(s) of interest in well-annotated cancer datasets. This visualization is accompanied by generation of reports customized to the interest of the researcher (e.g., editable figures, detailed statistical analyses, and access to raw data for reanalysis). It also carries out gene-to-gene correlations in multiple datasets at the same time or using preset patient groups. Finally, this new tool solves the time-consuming task of performing functional enrichment analysis with gene sets of interest using up to 11 different databases at the same time. Collectively, CANCERTOOL represents a simple and freely accessible interface to interrogate well-annotated datasets and obtain publishable representations that can contribute to refinement and guidance of cancer-related investigations at all levels of hypotheses and design. In order to facilitate access of research groups without bioinformatics support to public transcriptomics data, we have developed a free online tool with an easy-to-use interface that allows researchers to obtain quality information in a readily publishable format. .

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Section: Basic Analysesmentioning

confidence: 76%

Section: Basic Analysesmentioning

confidence: 97%

Section: Correlationsmentioning

confidence: 99%

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CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

et al. 2018

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“…CRYAB may be regulated by Ets1 (breast cancer) 47 , KLF4 (osteosarcoma) 48 , HSFI (hepatocellular carcinoma) 49 . Valcarcel-Jimenez et al 50 found MITF exerted tumor-suppressive activity in PCa, and CRYAB was the direct target of MITF. However, there was a complex regulatory network between molecules.…”

Section: Discussionmentioning

confidence: 99%

MiRNA-671-5p Promotes prostate cancer development and metastasis by targeting NFIA/CRYAB axis

et al. 2020

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Prostate cancer (PCa) is the second cause of death due to malignancy among men, and metastasis is the leading cause of mortality in patients with PCa. MicroRNAs (miRNAs) play important regulatory roles in tumor development and metastasis. Here, we identified 13 miRNAs related to PCa metastasis by bioinformatics analysis. Moreover, we found that miR-671-5p was increased in metastatic PCa tissues, and its high expression indicated poor prognosis of PCa. MiR-671-5p could facilitate PCa cells proliferation, migration, and invasion in vitro and vivo. We confirmed that miR-671-5p directly bound to the 3’ untranslated regions of NFIA mRNA, and NFIA directly bound to the CRYAB promoter. High expression of NFIA and CRYAB negatively correlated with the advanced clinicopathological characteristics and metastasis status of PCa patients. Our study demonstrated that miR-671-5p promoted PCa development and metastasis by suppressing NFIA/ CRYAB axis.

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“…Furthermore, MITF is involved in cell cycle regulation [ 11 , 12 ], cell survival [ 13 , 14 ], cell differentiation [ 15 ], and cell migration [ 16 , 17 ]. In addition to melanoma, several tumors are associated with the dysregulation of the MITF gene, including renal cell carcinoma [ 18 ], clear cell sarcoma [ 19 ], prostate cancer [ 20 ], and chronic myeloid leukemia [ 21 ], but there are no reports of its involvement in OvCa.…”

Section: Introductionmentioning

confidence: 99%

Microphthalmia-Associated Transcription Factor-Dependent Melanoma Cell Adhesion Molecule Activation Promotes Peritoneal Metastasis of Ovarian Cancer

Kitami

Yoshihara

Koya

et al. 2020

IJMS

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Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.

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Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer

Cited by 15 publications

References 66 publications

CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

MiRNA-671-5p Promotes prostate cancer development and metastasis by targeting NFIA/CRYAB axis

Microphthalmia-Associated Transcription Factor-Dependent Melanoma Cell Adhesion Molecule Activation Promotes Peritoneal Metastasis of Ovarian Cancer

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