A MicroRNA Targeting Dicer for Metastasis Control

Martello, Graziano; Rosato, Antonio; Ferrari, Francesco; Manfrin, Andrea; Cordenonsi, Michelangelo; Dupont, Sirio; Enzo, Elena; Guzzardo, Vincenza; Rondina, Maria; Spruce, Thomas; Parenti, Anna; Daidone, Maria Grazia; Bicciato, Silvio; Piccolo, Stefano

doi:10.1016/j.cell.2010.05.017

Cited by 605 publications

(548 citation statements)

References 46 publications

(48 reference statements)

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“…13,14 This is supported by a recent report, in which DICER was shown to be specifically targeted by the miR-103/107 family in breast cancer, where overexpression of miR-103/107 members induced epithelial-to-mesenchymal transition via reduced levels of miR-200b. 31 Therefore, direct regulation of DICER1 levels by miR-9 overexpression could contribute to transformation and invasiveness in HL.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo

et al. 2012

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MicroRNAs are important regulators of gene expression in normal development and disease. miR-9 is overexpressed in several cancer forms, including brain tumours, hepatocellular carcinomas, breast cancer and Hodgkin lymphoma (HL). Here we demonstrated a relevance for miR-9 in HL pathogenesis and identified two new targets Dicer1 and HuR. HL is characterized by a massive infiltration of immune cells and fibroblasts in the tumour, whereas malignant cells represent only 1% of the tumour mass. These infiltrates provide important survival and growth signals to the tumour cells, and several lines of evidence indicate that they are essential for the persistence of HL. We show that inhibition of miR-9 leads to derepression of DICER and HuR, which in turn results in a decrease in cytokine production by HL cells followed by an impaired ability to attract normal inflammatory cells. Finally, inhibition of miR-9 by a systemically delivered antimiR-9 in a xenograft model of HL increases the protein levels of HuR and DICER1 and results in decreased tumour outgrowth, confirming that miR-9 actively participates in HL pathogenesis and points to miR-9 as a potential therapeutic target.Oncogene ( Keywords: miR-9; cytokines; Hodgkin lymphoma; HuR; DICER1 INTRODUCTIONChronic inflammation is a well-recognized cause of cancer and up to 25% of all cancers are thought to be induced by either chronic infections or autoimmune diseases. 1 Inflammation not only works as a tumour-promoting agent but also influences other steps of tumorigenesis by inducing DNA damage, angiogenesis, invasion and metastasis. 2 Hodgkin lymphoma (HL) is one of the most frequent lymphomas in the western world 3 and it can be divided in several subtypes based on the morphology, composition of the infiltrates and the phenotype of the immune cells. The nodular sclerosis subtype is the most common subtype of classical HL (cHL) and accounts for about 60--70% of the cHL cases, followed by mixed cellularity cHL accounting for 20--25%.cHL is an unusual B-cell malignancy in which the tumour cells represent only 1% of the tumour bulk, whereas the vast majority of the cells are a mixture of infiltrating immune cells and fibroblasts actively attracted via chemokine secretion by the malignant cells, the so-called Hodgkin and Reed --Sternberg cells. 3 Several lines of evidence indicate that the infiltrating cells are necessary for the survival of the HL cells by providing growth and survival signals, and protection from NK cells. 3,4 MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level by base-pairing to target mRNAs and promoting transcript instability and/or translational repression. 5 Mature miRNAs derive from long hairpin precursors that are sequentially processed by the RNase-III-type enzymes DROSHA and DICER1, respectively. 5 miRNAs have been implicated in several physiological and pathological events and can act as both tumour suppressors and oncogenes. 6

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Section: Discussionmentioning

confidence: 99%

Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo

et al. 2012

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“…129 At the cellular level, one of the key events associated with miR-103/107 is the induction of EMT via the downregulation of miR-200 expression. 130 Song et al found that miR-22 triggered EMT, enhanced invasiveness, and promoted metastasis in mouse xenografts. They also demonstrated that miR-22 induced metastatic potential by silencing miR-200 through the targeting of ten-eleven translocation proteins, which are a family of methylcytosine dioxygenases.…”

Section: Mirna In Triple-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

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“…It often involves transforming growth factor (TGF)-b and SMAD (Derynck and Akhurst, 2007). EMT cells are presumed to be responsible for metastasis (Leroy et al, 1994;Christiansen and Rajasekaran, 2006;Alexander et al, 2008;Giampieri et al, 2009;Martello et al, 2010;Pantel and Alix-Panabieres, 2010). Here are some recent arguments for this statement.…”

Section: Epithelial-to-mesenchymal Transitionmentioning

confidence: 99%

Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

Floor¹,

Staveren²,

et al. 2011

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A MicroRNA Targeting Dicer for Metastasis Control

Cited by 605 publications

References 46 publications

Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo

Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

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