- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- RNA modifications and cancer
- Circular RNAs in diseases
- Prostate Cancer Treatment and Research
- RNA and protein synthesis mechanisms
- Pregnancy and preeclampsia studies
- Plant Stress Responses and Tolerance
- Extracellular vesicles in disease
- Plant Molecular Biology Research
- Cancer-related gene regulation
- Proteoglycans and glycosaminoglycans research
- Cancer Cells and Metastasis
- Bone and Joint Diseases
- Kruppel-like factors research
- Biomedical Text Mining and Ontologies
- Advanced Biosensing Techniques and Applications
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Wheat and Barley Genetics and Pathology
- FOXO transcription factor regulation
- Biomarkers in Disease Mechanisms
- Lymphatic System and Diseases
Centre for Cancer Biology
2015-2025
South Australia Pathology
2015-2025
University of South Australia
2015-2025
The University of Adelaide
2013-2025
Oregon State University
2013
Australian Centre for Plant Functional Genomics
2013
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, functioning in part by facilitating the degradation target mRNAs. They have an established role controlling epithelial-mesenchymal transition (EMT), a reversible phenotypic program underlying normal and pathological processes. Many studies demonstrate individual miRNAs using overexpression at levels greatly exceeding physiological abundance. This can influence transcripts with relatively poor targeting may...
Article6 June 2018Open Access Source DataTransparent process miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking Katherine A Pillman orcid.org/0000-0002-5869-889X Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Search more papers this author Caroline Phillips Suraya Roslan John Toubia B Kate Dredge Andrew G Bert Rachael Lumb Daniel P Neumann Xiaochun Li Simon J Conn...
p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs) regulate and themselves are direct transcriptional targets. We show here group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar (sno-miRNAs) transcriptionally repressed by through their host gene, SNHG1. The most abundant these, sno-miR-28, directly targets the p53-stabilizing TAF9B. Collectively, p53, SNHG1, sno-miR-28 TAF9B form loop...
Deep-sequencing reveals extensive variation in the sequence of endogenously expressed microRNAs (termed 'isomiRs') human cell lines and tissues, especially relation to 3′ end. From immunoprecipitation microRNA-binding protein Argonaute sequencing associated small RNAs, we observe 3′-isomiR variation, including for miR-222 where majority is extended by 1–5 nt compared canonical sequence. We demonstrate this heterogeneity has dramatic implications phenotype transfected cells, with longer...
Potent therapeutic inhibition of the androgen receptor (AR) in prostate adenocarcinoma can lead to emergence neuroendocrine cancer (NEPC), a phenomenon associated with enhanced cell plasticity. Here, we show that microRNA-194 (miR-194) is regulator epithelial-neuroendocrine transdifferentiation. In clinical samples, miR-194 expression and activity were elevated NEPC inversely correlated AR signaling. facilitated features cells, process mediated by its ability directly target suite genes...
Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes gene expression. While it well established that post-transcriptional regulation a significant role EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3' end anchored RNA sequencing, we mapped landscape following Transforming Growth Factor (TGF)-β-mediated induction human mammary epithelial cells found APA generally causes...
Abstract While the majority of circRNAs are formed from infrequent back-splicing exons protein coding genes, some can be produced at quite high level and in a regulated manner. We describe regulation, biogenesis function circDOCK1(2–27), large, abundant circular RNA that is highly during epithelial-mesenchymal transition (EMT) whose formation depends on epithelial splicing regulator ESRP1. CircDOCK1(2–27) synthesis cells represses cell motility both by diverting transcripts DOCK1 mRNA...
High-throughput sequencing reveals an abundance of microRNA-sized fragments derived from larger non-coding RNAs. Roles for these small RNAs in gene silencing are suggested by their co-precipitation with Argonaute, the microRNA effector protein, though extent to which they suppress expression endogenously remains unclear. To address this, we used luciferase reporters determine endogenous functionality a diverse range sources. We demonstrate snoRNAs have capacity act microRNA-like manner, note...
MicroRNAs (miRNAs) are increasingly seen as important regulators of placental development and opportunistic biomarker targets. Given the difficulty in obtaining samples from early gestation subsequent paucity same, investigation role miRNAs human placenta has been limited. To address this, we generated miRNA profiles using 96 placentas presumed normal pregnancies, across gestation, combination with matched maternal plasma. Placenta range 6 to 23 weeks' a time period that includes early,...
MiRNAs post-transcriptionally repress gene expression by binding to mRNA 3'UTRs, but the extent which they act through protein coding regions (CDS regions) is less well established. MiRNA interaction studies show a substantial proportion of occurs in CDS regions, however sequencing much weaker effects on levels than from 3'UTR interactions, presumably due competition translating ribosome. Consequently, most target prediction algorithms consider only interactions. However, consequences...
MicroRNAs (miRNAs) are important regulators of gene expression whose dysregulation is widely linked to tumourigenesis, tumour progression and Epithelial-Mesenchymal Transition (EMT), a developmental process that promotes metastasis when inappropriately activated. However, controversy has emerged regarding how many functional miRNAs encoded in the genome, what extent non-regulatory products RNA degradation have been mis-identified as miRNAs. Central miRNA function their capacity associate...
Background and Aims: Genetic heterogeneity in ovarian cancer drives frequent aberrant expression of cell surface proteins including G-protein coupled receptors (GPCRs), which harbour untapped potential for active targeting with nanomedicines. Our goal was to systematically identify GPCRs significant overexpression biopsies assessing their suitability develop personalized GPCR-targeted nanomedicines precise drug delivery. Methods: We ran a systematic analysis public RNA-seq gene data, reveal...
Endogenous microRNAs (miRNAs) often exist as multiple isoforms (known “isomiRs”) with predominant variation around their 3′-end. Increasing evidence suggests that different isomiRs of the same family can have diverse functional roles, recently demonstrated example miR-222-3p 3′-end variants. While isomiR levels from a miRNA vary between tissues and cell types, change templated stoichiometry to stimulation has not been reported date. Relying on small RNA-sequencing analyses, we demonstrate...
Expression of the wheat dehydrin gene Cor410b is induced several fold above its non-stressed levels upon exposure to stresses such as cold, drought and wounding. Deletion analysis TdCor410b promoter revealed a single functional C-repeat (CRT) element. Seven transcription factors (TFs) were shown bind this CRT element using yeast one-hybrid screens barley cDNA libraries, which only one belonged DREB class TFs. The remaining six encoded ethylene response (ERFs) belong three separate...
The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed locus for epigenetic modifications in breast epithelial mesenchymal cell lines using chromatin immunoprecipitation assays DNA methylation analysis. discovered novel enhancer located approximately 5.1kb upstream transcriptional start site. This region was associated with active...
The abundance of cell-free microRNA (miRNA) has been measured in blood plasma and proposed as a source novel, minimally invasive biomarkers for several diseases. Despite improvements quantification methods, there is no consensus regarding how haemolysis affects miRNA content. We propose method detection high-throughput sequencing (HTS) data from libraries prepared using human plasma. To establish signature we tested differential between samples with known status. Using these miRNAs...
Most microRNAs (miRNAs) are expressed as a mix of length isoforms (referred to isomiRs). IsomiR stoichiometry can be differentially impacted upon cell stimulation, recently evidenced by our group in the context immune responses induced type-I interferon (IFN). Here, we revisit published RNA-seq data sets human and mouse macrophages stimulated with bacterial products at isomiR level. We demonstrate that for several miRNAs, macrophage stimulation induces changes stoichiometry. Critically, find...
Abstract The attachment of unique molecular identifiers (UMIs) to RNA molecules prior PCR amplification and sequencing, makes it possible amplify libraries a level that is sufficient identify rare molecules, whilst simultaneously eliminating bias through the identification duplicated reads. Accurate de-duplication dependent upon sufficiently complex pool UMIs allow labelling. In applications dealing with libraries, such as total RNA-seq, only limited variety are required variation in be...
Epithelial-mesenchymal transition is essential for tissue patterning and organization. It involves both regulation of cell motility alterations in the composition organization ECM-a complex environment proteoglycans fibrous proteins homeostasis, signaling response to chemical biomechanical stimuli, often dysregulated under conditions such as cancer, fibrosis, chronic wounds. Here, we demonstrate that basonuclin-2 (BNC2), a mesenchymal-expressed gene, is, strongly associated with cancer...