Publications
73 results found
Ali S, Patel H, Periyasamy M, et al., 2016, ICEC0942, an orally bioavailable selective inhibitor of CDK7 for breast cancer, UK Breast Cancer Research Symposium, Publisher: Springer Verlag, Pages: 195-195, ISSN: 0167-6806
Miller HC, Frampton AE, Malczewska A, et al., 2016, MicroRNAs associated with small bowel neuroendocrine tumours and their metastases, Endocrine-Related Cancer, Vol: 23, Pages: 711-726, ISSN: 1479-6821
Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n=90), including primary SBNETs (n=28), adjacent normal small bowel (NSB; n=14), matched lymph node (LN) metastases (n=24), normal LNs (n=7), normal liver (n=2) and liver metastases (n=15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA–mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.
Stebbing J, Frampton AE, Miller HC, et al., 2016, MicroRNAs associated with small bowel neuroendocrine tumors and their metastases., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Lin M-L, Patel H, Remenyi J, et al., 2015, Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer, Oncotarget, Vol: 6, Pages: 21685-21703, ISSN: 1949-2553
he Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-α (ERα), which is a key therapeutic target. ERα action is facilitated by co-operativity with other NR and there is evidence that ERα function may be recapitulated by other NRs in ERα-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERα and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORγ is identified as being co-expressed with ERα, whilst several NRs are preferentially expressed in ERα-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERα-negative breast cancer cells.
Cathcart P, Lucchesi W, Ottaviani S, et al., 2015, Noncoding RNAs and the control of signalling via nuclear receptor regulation in health and disease, BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 29, Pages: 529-543, ISSN: 1521-690X
Ottaviani S, de Giorgio A, Harding V, et al., 2014, Noncoding RNAs and the control of hormonal signaling via nuclear receptor regulation, JOURNAL OF MOLECULAR ENDOCRINOLOGY, Vol: 53, Pages: R61-R70, ISSN: 0952-5041
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- Citations: 8
Krell J, Frampton AE, Mirnezami R, et al., 2014, Growth Arrest-Specific Transcript 5 Associated snoRNA Levels Are Related to p53 Expression and DNA Damage in Colorectal Cancer, PLOS One, Vol: 9, ISSN: 1932-6203
Background: The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts anumber of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer.Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into thepotential role of this locus in cell survival and oncogenesis both in vivo and in vitro.Methods: We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assessthe relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignanthuman colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damageresponse.Results: GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancercell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNAexpression in colorectal tissue.Conclusions: In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they havean important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome.We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used asendogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experimentscan lead to inaccurate results.
Lai C-F, Flach KD, Alexi X, et al., 2013, Co-regulated gene expression by oestrogen receptor α and liver receptor homolog-1 is a feature of the oestrogen response in breast cancer cells, NUCLEIC ACIDS RESEARCH, Vol: 41, Pages: 10228-10240, ISSN: 0305-1048
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- Citations: 36
Ottaviani S, Brooke GN, O'Hanlon-Brown C, et al., 2013, Characterisation of the androgen regulation of glycine <i>N</i>-methyltransferase in prostate cancer cells, JOURNAL OF MOLECULAR ENDOCRINOLOGY, Vol: 51, Pages: 301-312, ISSN: 0952-5041
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- Citations: 13
Pellegrino L, Stebbing J, Braga VM, et al., 2013, miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts, Nucleic Acids Research, Vol: 41, Pages: 5400-5412, ISSN: 1362-4962
Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.
Alshaker H, Sauer L, Monteil D, et al., 2013, Therapeutic Potential of Targeting SK1 in Human Cancers, ROLE OF SPHINGOLIPIDS IN CANCER DEVELOPMENT AND THERAPY, Vol: 117, Pages: 143-200, ISSN: 0065-230X
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- Citations: 40
Ottaviani S, Brown CO, Waxman J, et al., 2012, Identification of glycine N-methyltransferase-regulated genes in prostate cancer cells, CANCER RESEARCH, Vol: 72, ISSN: 0008-5472
Castellano L, Ottaviani S, Frampton AE, ATGF-β-lin28b-miRNA Circuit Regulates EMT and Stemness in Pancreatic Cancer, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 1393-1393, ISSN: 0885-3177
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