miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response

Mateescu, Bogdan; Batista, Luciana; Cardon, Mélissa; Gruosso, Tina; Feraudy, Yvan de; Mariani, Odette; André, Nathalie; Meyniel, Jean-Philippe; Cottu, Paul; Sastre-Garau, Xavier; Mechta‐Grigoriou, Fatima

doi:10.1038/nm.2512

Cited by 434 publications

(430 citation statements)

References 60 publications

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“…These results intensively imply that miR-141 acts as an inhibitor of pancreatic cancer tumorigenesis. Our data are in accordance with those of Du and colleagues (25) who showed miR-141 inhibited the proliferation of gastric cancer cells, but is in contrast to other studies that suggest miR-141 acts as an oncogene in ovarian (20) and colon cancers (21). These observations suggest that miR-141 has a heterogeneous role in tumorigenesis that may be highly dependent on its targets in different cells.…”

Section: Discussionsupporting

confidence: 92%

“…Recent data have shown that miR-141 and miR-200c play important roles in tumorigenesis. For example, miR-141 increases in ovarian cancer (20) and colon cancer (21) and acts as an oncogene. Other researches show miR-141 is downregulated in renal cell carcinoma (22), breast cancer (23), and pancreatic cancer (24), and can inhibit cell growth in gastric cancer (25).…”

Section: Introductionmentioning

confidence: 99%

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miRNA-141, Downregulated in Pancreatic Cancer, Inhibits Cell Proliferation and Invasion by Directly Targeting MAP4K4

Zhao

Wang

Liu

et al. 2013

Molecular Cancer Therapeutics

138

110

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miRNAs are associated with various types of cancer due to their ability to affect expression of genes that modulate tumorigenesis. In this study, we explored the role of miR-141 in pancreatic cancer. The analysis of clinical characteristics showed that miR-141 was significantly downregulated in tissues and cell lines of pancreatic cancer. Moreover, the decreased miR-141 level was significantly associated with tumor size and TNM stage, as well as lymph node and distant metastasis. Meanwhile, both Kaplan-Meier and multivariate survival analysis showed decreased miR-141 were associated with overall survival. Overexpression of miR-141 in pancreatic cancer cells inhibited cell proliferation, clonogenicity, and invasion; induced G 1 arrest and apoptosis; and enhanced chemosensitivity. To understand how miR-141 mediates the phenotype of pancreatic cancer cells, a bioinformatics tool was used to identify MAP4K4 as a potential target of miR-141. The DualLuciferase reporter gene assay showed that miR-141 binds directly to the 3 0 -untranslated region (3 0 UTR) of MAP4K4 to inhibit MAP4K4 expression. Western blot and quantitative real-time PCR (qRT-PCR) analyses revealed that MAP4K4 expression was inversely correlated with miR-141 expression both in pancreatic cancer samples and cell lines. Knockdown of MAP4K4 inhibited cell proliferation, clonogenicity, and invasion, induced G 1 arrest and apoptosis, and enhanced chemosensitivity. In a nude mouse xenograft model, both overexpression of miR-141 and knockdown of MAP4K4 significantly repressed pancreatic cancer cell growth. Therefore, we conclude that miR-141 targets MAP4K4, acts as a tumor suppressor in pancreatic cancer cells, and may serve as a novel therapeutic agent for miRNA-based pancreatic cancer therapy. Mol Cancer Ther; 12(11); 2569-80. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

miRNA-141, Downregulated in Pancreatic Cancer, Inhibits Cell Proliferation and Invasion by Directly Targeting MAP4K4

Zhao

Wang

Liu

et al. 2013

Molecular Cancer Therapeutics

138

110

View full text Add to dashboard Cite

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“…miR-141 and miR-200a have been found to act as repressors of Dlx5 and Osx expression, and it has been demonstrated that both bind to Dlx5 mRNA in vitro (Itoh et al 2009). Moreover, miR-141 and miR-200a target p38a (Mapk14) in mouse models of ovarian cancer, in agreement with previous screenings in human ovarian adenocarcinomas (Mateescu et al 2011). Positive effects of p38 phosphorylation have been observed on Dlx5 transcriptional activity and on Osx stability (Ulsamer et al 2008, Ortuno et al 2010; consequently, the activity of miR-141 and miR-200a in osteoblast lineages is also probably mediated by changes in p38 phosphorylation of Dlx5 and Osx.…”

Section: Mirnas and Osteoblast Differentiationsupporting

confidence: 88%

MicroRNAs and post-transcriptional regulation of skeletal development

Gámez¹,

Rodríguez-Carballo²,

Ventura³

2014

Journal of Molecular Endocrinology

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MicroRNAs (miRNAs) have become integral nodes of post-transcriptional control of genes that confer cellular identity and regulate differentiation. Cell-specific signaling and transcriptional regulation in skeletal biology are extremely dynamic processes that are highly reliant on dose-dependent responses. As such, skeletal cell-determining genes are ideal targets for quantitative regulation by miRNAs. So far, large amounts of evidence have revealed a characteristic temporal miRNA signature in skeletal cell differentiation and confirmed the essential roles that numerous miRNAs play in bone development and homeostasis. In addition, microarray expression data have provided evidence for their role in several skeletal pathologies. Mouse models in which their expression is altered have provided evidence of causal links between miRNAs and bone abnormalities. Thus, a detailed understanding of the function of miRNAs and their tight relationship with bone diseases would constitute a powerful tool for early diagnosis and future therapeutic approaches.

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“…Some of the first studies demonstrated that the expression of the miR-200 family was correlated with the epithelial/mesenchymal phenotype of ovarian cancer cell lines . This study as well as other studies (Bendoraite et al 2010) demonstrated that miR-200a/b/c, miR-141, and miR-429 determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressor proteins ZEB1 and ZEB2 as well as regulating oxidative stress via p38a (Mateescu et al 2011).…”

Section: Ndsupporting

confidence: 75%

The role of micro-RNAs in the female reproductive tract

Nothnick

2012

Reproduction

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Proper development and function of the female reproductive tract are essential for successful reproduction. Regulation of the differentiated functions of the organs that make up the female reproductive tract is well established to occur at multiple levels including transcription, translation, and posttranslational modifications. Micro-RNA (miRNA)-mediated posttranscriptional gene regulation has emerged as a fundamental mechanism controlling normal tissue development and function. Emerging evidence indicates that miRNAs are expressed within the organs of the female reproductive tract where they function to regulate cellular pathways necessary for proper function of these organs. In this review, the functional significance of miRNAs in the development and function of the organs of the female reproductive tract is discussed. Initial discussion focuses on the role of miRNAs in the development of the organs of the female reproductive tract highlighting recent studies that clearly demonstrate that mice with disrupted Dicer1 expression are sterile, fail to develop uterine glands, and have muted estrogen responsiveness. Next, emphasis moves to discussion on our current knowledge on the characterization of miRNA expression in each of the organs of the female reproductive tract. When possible, information is presented and discussed with respect to regulation, function, and/or functional targets of these miRNA within each specific organ of the female reproductive tract.

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miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response

Cited by 434 publications

References 60 publications

miRNA-141, Downregulated in Pancreatic Cancer, Inhibits Cell Proliferation and Invasion by Directly Targeting MAP4K4

miRNA-141, Downregulated in Pancreatic Cancer, Inhibits Cell Proliferation and Invasion by Directly Targeting MAP4K4

MicroRNAs and post-transcriptional regulation of skeletal development

The role of micro-RNAs in the female reproductive tract

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