Post-transcriptional Regulation of Human Breast Cancer Cell Proteome by Unliganded Estrogen Receptor β via microRNAs

Nassa, Giovanni; Tarallo, Roberta; Giurato, Giorgio; Filippo, Maria Rosaria De; Ravo, Maria; Rizzo, Francesca; Stellato, Claudia; Ambrosino, Concetta; Baumann, Marc; Lietzén, Niina; Nyman, Tuula A.; Weisz, Alessandro

doi:10.1074/mcp.m113.030403

Cited by 34 publications

(40 citation statements)

References 79 publications

(95 reference statements)

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“…The data obtained from the sequencer were analyzed using iMir, a modular pipeline for comprehensive analysis of small RNA-Seq data, comprising specific tools for adapter trimming, quality filtering, identification of known sncRNAs, novel miRNA prediction, differential expression analysis and target prediction [72, 73]. …”

Section: Methodsmentioning

confidence: 99%

“…Identification of differentially expressed sncRNAs was performed with the Bioconductor DESeq package available in iMir tool [72, 73]. A negative binomial distribution model was used to test differential expression in deep sequencing datasets.…”

Section: Methodsmentioning

confidence: 99%

“…Gene expression profiling was performed using 500 ng of each RNA Pool as described before [73]. For each Pool, 750 ng of cRNA were hybridized for 18 hrs at 55°C on Illumina HumanHT-12 v4.0 BeadChips (Illumina Inc.), according to the manufacturer's instructions and subsequently scanned with the Illumina iSCAN.…”

Section: Methodsmentioning

confidence: 99%

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Small non-coding RNA deregulation in endometrial carcinogenesis

et al. 2015

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Small non-coding RNAs (sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising microRNAs, PIWI-interacting RNAs (piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and pathological processes such as carcinogenesis and tumor progression. Aberrant sncRNA expression in cancer has been associated with specific clinical phenotypes, grading, staging, metastases development and resistance to therapy.Aim of the present work is to study the role of sncRNAs in endometrial carcinogenesis. Changes in sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies (n = 10). Using smallRNA sequencing and microarrays we identified significant differences in sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a sncRNA signature (129 microRNAs, 2 of which not previously described, 10 piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-catenin, and ERK/MAPK and TGF-β-Signaling.Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Small non-coding RNA deregulation in endometrial carcinogenesis

et al. 2015

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“…2E) [3,73,74]. In BC, unliganded ER␣ has been found able to regulate genes linked to development and differentiation [27] while unliganded ER␤ strongly affects both the genome and the proteome of BC cells by inducing also microRNA expression changes [75,76]. In prostate cancer, the presence of unliganded ER␤ seems to induce apoptosis by a KLF5 tethering mechanism [77].…”

Section: Ligand-independent Signalingmentioning

confidence: 96%

“…A first study reported the effect of unliganded ER␤ expression on BC cell miRNome [109]. Subsequently, Nassa et al [75], considering that ER␤ subtype seems to be the most active in absence of ligand and taking into account its inhibitory role in respect to ER␣ in BC, investigated the activity of unliganded ER␤ in MCF-7 and ZR-75.1 BC cell lines by means of microRNA sequencing (miRNA-Seq). They found 30 miRNAs affected by the presence of unliganded ER␤.…”

Section: Unliganded Ers and Regulation Of Noncoding Rna And Proteomementioning

confidence: 99%

The “busy life” of unliganded estrogen receptors

et al. 2015

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Understanding of the role of estrogen receptors (ERα and ERβ) in the pathophysiology of breast cancer (BC) has considerably increased in last decades. Despite sharing a similar structure, these two transcription factors often exert opposite roles in BC. In addition, it has been shown that their transcriptional activity is not strictly associated to ligand activation and that unliganded ERs are able to "have a life on their own." This appears to be mainly due to ligand-independent mechanisms leading to ERs PTMs or to their recruitment to specific protein complexes, dependent on cellular context. Furthermore, a significant unliganded ER activity, probably independent by the activation of other pathways, has been recently reported to affect gene transcription, microRNA expression, and downstream proteome. In this review, we describe recent findings on nuclear and cytoplasmic unliganded ERα and ERβ activity. We focus on functional genomics, epigenomics, and interaction proteomics data, including PTM induced by ERs-modulated miRNAs in the BC context. A better comprehension of the molecular events controlled by unliganded ERs activity in BC pathogenesis is crucial since it may impact the therapeutic approach to the initial or acquired resistance to endocrine therapies, frequently experienced in the treatment of BC.

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Identification of Genes Selectively Regulated in Human Hepatoma Cells by Treatment With Dyslipidemic Sera and PUFAs

Rosa

Caputo

Zirpoli

et al. 2015

Journal Cellular Physiology

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Serum composition is linked to metabolic diseases not only to understand their pathogenesis but also for diagnostic purposes. Quality and quantity of nutritional intake can affect disease risk and serum composition. It is then possible that diet derived serum components directly affect pathogenetic mechanisms. To identify involved factors, we evaluated the effect on gene expression of direct addition of dyslipidemic human serum samples to cultured human hepatoma cells (HepG2). Sera were selected on the basis of cholesterol level, considering this parameter as mostly linked to dietary intake. Cells were treated with 32 sera from hypercholesterolemic and normocholesterolemic subjects to identify differentially regulated mRNAs using DNA microarray analysis. We identified several mRNAs with the highest modulations in cells treated with dyslipidemic sera versus cells treated with normal sera. Since the two serum groups had variable polyunsaturated fatty acids (PUFAs) contents, selected mRNAs were further assessed for their regulation by docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AA). Four genes resulted both affected by serum composition and PUFAs: 3-hydroxy-3-methylglutaryl-CoenzymeA synthase 2 (HMGCS2), glutathione S-transferase alpha 1 (GSTA1), liver expressed antimicrobial peptide 2 (LEAP2) and apolipoprotein M (ApoM). HMGCS2 expression appears the most relevant and was also found modulated via transcription factors peroxysome proliferator activated receptor α (PPARα) and forkhead box O1 (FoxO1). Our data indicate that expression levels of the selected mRNAs, primarily of HMGCS2, could represent a reference of nutritional intake, PUFAs effects and dyslipidemic diseases pathogenesis.

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Post-transcriptional Regulation of Human Breast Cancer Cell Proteome by Unliganded Estrogen Receptor β via microRNAs

Abstract: Estrogen receptor ␤ (ER␤) is

Cited by 34 publications

References 79 publications

Small non-coding RNA deregulation in endometrial carcinogenesis

Small non-coding RNA deregulation in endometrial carcinogenesis

The “busy life” of unliganded estrogen receptors

Identification of Genes Selectively Regulated in Human Hepatoma Cells by Treatment With Dyslipidemic Sera and PUFAs

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