Dietary alterations modulate the microRNA 29/30 and IGF-1/AKT signaling axis in breast Cancer liver metastasis (original) (raw)
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Physiological …, 2011
1160: Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: Effect of a.JR, Ivanov I, Chapkin RS. Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: effect of a chemoprotective diet. We have recently demonstrated that nutritional bioactives (fish oil and pectin) modulate microRNA molecular switches in the colon. Since integrated analysis of microRNA and mRNA expression at an early stage of colon cancer development is lacking, in this study, four computational approaches were utilized to test the hypothesis that microRNAs and their posttranscriptionally regulated mRNA targets, i.e., both total mRNAs and actively translated mRNA transcripts, are differentially modulated by carcinogen and diet treatment. Sprague-Dawley rats were fed diets containing corn oil Ϯ fish oil with pectin Ϯ cellulose and injected with azoxymethane or saline (control). Colonic mucosa was assayed at an early time of cancer progression, and global gene set enrichment analysis was used to obtain those microRNAs significantly enriched by the change in expression of their putative target genes. In addition, cumulative distribution function plots and functional network analyses were used to evaluate the impact of diet and carcinogen combination on mRNA levels induced via microRNA alterations. Finally, linear discriminant analysis was used to identify the best single-, two-, and three-microRNA combinations for classifying dietary effects and colon tumor development. We demonstrate that polysomal profiling is tightly related to microRNA changes when compared with total mRNA profiling. In addition, diet and carcinogen exposure modulated a number of microRNAs (miR-16, miR-19b, miR-21, miR26b, miR27b, miR-93, and miR-203) linked to canonical oncogenic signaling pathways. Complementary gene expression analyses showed that oncogenic PTK2B, PDE4B, and TCF4 were suppressed by the chemoprotective diet at both the mRNA and protein levels.
Faculty of 1000 evaluation for Endogenous human microRNAs that suppress breast cancer metastasis
F1000 - Post-publication peer review of the biomedical literature, 2008
A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo. Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 inhibits metastatic cell invasion. miR-335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer. Although metastasis is the overwhelming cause of mortality in patients with solid tumours, our understanding of its molecular and cellular determinants is limited 1-3. Transcriptional profiling has revealed sets of genes, or `signatures', for which expression in primary tumours correlates with metastatic relapse or poor survival 4. Some of these genes endow cancer cells with a more invasive phenotype, enhanced angiogenic and intravasation activity, the ability to exit from the circulation, or an ability to modify the metastasis microenvironment 5,6. Such gene sets are thus providing numerous candidate mediators of metastasis to be validated through functional and clinical studies. Much less insight, however, has been gained into the ©2007 Nature Publishing Group Author Information The miR-335 microarray data is deposited at GEO under accession number GSE9586. Reprints and permissions information is available at www.nature.com/reprints. Correspondence and requests for materials should be addressed to J.M.
The Impact of microRNAs in Breast Cancer Angiogenesis and Progression
MicroRNA, 2019
Objective: The study aims to review the recent data considering the expression profile and the role of microRNAs in breast tumorigenesis, and their impact on -the vital for breast cancer progression- angiogenesis. Methods: PubMed was searched for studies focused on data that associate microRNA with breast cancer, using the terms ''breast”, “mammary gland”, “neoplasia'', “angiogenesis” and ''microRNA'' between 1997-2018. Results: Aberrant expression of several circulating and tissue miRNAs is observed in human breast neoplasms with the deregulation of several miRNAs having a major participation in breast cancer progression. Angiogenesis seems to be directly affected by either overexpression or down regulation of many miRNAs, defining the overall prognostic rates. Many miRNAs differentially expressed in breast cancer that reveal a key role in suppression - progression and metastasis of breast cancer along with the contribution of the EGF, TNF-a and EGF ...
Interplay Between Metabolism and Oncogenic Process: Role of microRNAs
Translational Oncogenomics, 2015
Cancer is a complex disease that arises from the alterations in the composition and regulation of several genes leading to the disturbances in signaling pathways, resulting in the dysregulation of cell proliferation and death as well as the ability of transformed cells to invade the host tissue and metastasize. It is increasingly becoming clear that metabolic reprograming plays a critical role in tumorigenesis and metastasis. Therefore, target ing this phenotype is considered as a promising approach for the development of therapeutics and adjuvants. The process of metabolic reprograming is linked to the activation of oncogenes and/or suppression of tumor suppressor genes, which are further regulated by microRNAs (miRNAs) that play important roles in the interplay between oncogenic process and metabolic reprograming. Looking at the advances made in the recent past, it appears that the translation of knowledge from research in the areas of metabolism, miRNA, and therapeutic response will lead to paradigm shift in the management of this disease.
Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity
Cancers
Background: Several studies have shown that healthy lifestyles prevent the risk of breast cancer (BC) and are associated with better prognosis. It was hypothesized that lifestyle strategies induce microRNA (miRNA) modulation that, in turn, may lead to important epigenetic modifications. The identification of miRNAs associated with BC, diet, and physical activity may give further insights into the role played by lifestyle interventions and their efficacy for BC patients. To predict which miRNAs may be modulated by diet and physical activity in BC patients, the analyses of different miRNA expression datasets were performed. Methods: The GEO DataSets database was used to select miRNA expression datasets related to BC patients, dietary interventions, and physical exercise. Further bioinformatic approaches were used to establish the value of selected miRNAs in BC development and prognosis. Results: The analysis of datasets allowed the selection of modulated miRNAs associated with BC deve...
MicroRNAs in pancreatic cancer metabolism
Nature Reviews Gastroenterology & Hepatology, 2012
Advances in understanding the biology of tumour progression and metastasis have clearly highlighted the importance of aberrant tumour metabolism, which supports not only the energy requirements but also the enormous biosynthetic needs of tumour cells. Such metabolic alterations modulate glucose, amino acid and fatty-acid-dependent metabolite bio-synthesis and energy production. Although much progress has been made in understanding the somatic mutations and expression genomics behind these alterations, the regulation of these processes by microRNAs (miRNAs) is only beginning to be appreciated. This Review focuses on the miRNAs that are potential regulators of the expression of genes whose protein products either directly regulate metabolic machinery or serve as master regulators, indirectly modulating the expression of metabolic enzymes. We focus particularly on miRNAs in pancreatic cancer.
MicroRNA-710 regulates multiple pathways of carcinogenesis in murine metastatic breast cancer
PLOS ONE
Prior research has shown that critical differences between non-metastatic and metastatic tumor cells are at the level of microRNA. Consequently, harnessing these molecules for the treatment of metastatic cancer could have significant clinical impact. In the present study, we set out to identify metastasis-specific microRNAs which drive metastatic colonization of distant organs. Using a murine model of metastatic breast cancer, we employed a directed approach in which we screened for microRNAs that are differentially expressed between the primary tumors and metastatic lesions but concordantly expressed in all of the metastatic lesions irrespective of the tissue that is colonized. Of the identified targets, we focused on miR-710, which was consistently and significantly downregulated in the metastatic lesions relative to the primary tumors. The level of downregulation was independent of the distant organ that is involved, suggesting that miR-710 plays a fundamental role in metastatic colonization. Computational target prediction suggested a pleiotropic role for miR-710 in apoptosis, migration and invasion, and stemness. Using a previously validated oligonucleotide delivery system, we introduced miR-710 mimics into 4T1 metastatic breast adenocarcinoma cells and assessed the resultant phenotypic effects. We demonstrated significant inhibition of cell viability, migration, and invasion. We also showed that the treatment profoundly enhanced cell senescence, reduced stemness, and influenced markers of epithelial to mesenchymal transition, as evidenced by enhanced E-cadherin and reduced vimentin expression. This knowledge represents a first step towards harnessing a similar approach to discover novel microRNA targets with therapeutic potential in metastasis. OPEN ACCESS Citation: Yoo B, Meka N, Sheedy P, Billig A-M, Pantazopoulos P, Medarova Z (2019) MicroRNA-710 regulates multiple pathways of carcinogenesis in murine metastatic breast cancer. PLoS ONE 14 (12): e0226356. https://doi.org/10.
MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis
International Journal of Molecular Sciences, 2016
The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic reprogramming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance.
MicroRNA involvement in the pathogenesis and management of breast cancer
Journal of Clinical Pathology, 2009
MicroRNAs (miRNAs) are a highly abundant class of endogenous small non-coding RNAs (18–25 nucleotides in length) that regulate gene expression by targeting protein-coding mRNAs post-transcriptionally. miRNAs have been implicated in cancer development and progression. As miRNAs and their regulatory functions are further revealed, the more the importance of miRNA-directed gene regulation is emphasised. In the human genome, 695 mature miRNAs have been identified, although computational calculation predicts that this may increase to >1000. Deregulation of miRNA expression profiles is thought to be implicated in the pathogenesis of many human cancers including breast tumours. Breast cancer subtypes are observed to have deranged miRNA expression signatures, which makes miRNAs important targets for developing a novel molecular classification of breast cancer and opening avenues for more individualised treatment strategies for patients with breast cancer.
Dietary Methyl Deficiency, microRNA Expression and Susceptibility to Liver Carcinogenesis
Journal of Nutrigenetics and Nutrigenomics, 2010
MicroRNAs (miRNAs) are small 21-25 nucleotide-long non-coding RNAs that have emerged as key negative post-transcriptional regulators of gene expression [1, 2]. Currently there are more than 700 mammalian miRNAs that can potentially target up to one-third of protein-coding human genes [1] involved in diverse physiological and pathological processes, including cancer [3, 4]. Indeed, aberrant levels of miRNAs have been reported in all major human malignancies [5, 6]. In tumors, altered expression of miRNAs has been demonstrated to inhibit tumor suppressor genes or inappropriately activate oncogenes and has been associated with every aspect of tumor biology, including tumor progression, invasiveness, metastasis, and acquisition of resistance by malignant cells to chemotherapeutic agents [3, 4, 7, 8]. These observations lead to the suggestion that aberrant expression of miRNAs may contribute to tumorigenesis [9]. However, most of the tumor-miRNA-related studies are based on expression analysis of miRNAs in tumors in comparison with corresponding adjacent normal tissues [4-6]. The altered expression of any given miRNA in neoplastic cells is not sufficient to address conclusively the role of these changes in tumorigenesis [10]. Additionally, despite the established biological significance of miRNA dysregulation in neoplastic cells, there is a lack of knowledge on the role of miRNAs during early stages of tumor development, especially if variations in the expression of specific miRNAs are associated with differences in the susceptibility to tumorigenesis.