A5049466429- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Cancer-related gene regulation
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Gut microbiota and health
- Peptidase Inhibition and Analysis
- Diet and metabolism studies
- Immune cells in cancer
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Diet, Metabolism, and Disease
- Helicobacter pylori-related gastroenterology studies
- Gene expression and cancer classification
- Biochemical and Molecular Research
- Liver physiology and pathology
- Ion Transport and Channel Regulation
- Intracerebral and Subarachnoid Hemorrhage Research
- Peroxisome Proliferator-Activated Receptors
- Coronary Artery Anomalies
- Tryptophan and brain disorders
- Gene Regulatory Network Analysis
- Neuroblastoma Research and Treatments
The University of Sydney
2020-2025
Centenary Institute
2020-2025
University of Technology Sydney
2014-2016
Neuroblastoma is the most common solid tumor during early childhood. One of key features neuroblastoma extensive tumor-driven angiogenesis due to hypoxia. However, mechanism through which cells drive poorly understood. Here we show that long noncoding RNA MALAT1 was upregulated in human cell lines under hypoxic conditions. Conditioned media from transfected with small interfering RNAs (siRNA) targeting MALAT1, compared conditioned control siRNAs, induced significantly less endothelial...
Intensive research based on the inverse expression relationship has been undertaken to discover miRNA-mRNA regulatory modules involved in infection of Hepatitis C virus (HCV), leading cause chronic liver diseases. However, biological studies other fields have found that is not only between miRNAs and their targets, some can positively regulate a mRNA by binding at 5' UTR mRNA. This work focuses detection both positive relationships from paired miRNA data set HCV patients through...
Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in development function these cells. Using Illumina mRNA sequencing, Nanopore direct cDNA sequencing proteomics analysis, identify IR events affect expression key genes/proteins involved macrophage function. We demonstrate decreased nuclear-detained is coupled with increased genes encoding regulators transcription, phagocytosis inflammatory...
Abstract Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function this mark ESCs differentiating embryoid bodies. Transcriptome-wide mapping reveals hundreds messenger RNAs marked by 5hmC at sites characterized defined unique consensus sequence particular features....
DNA methyltransferases (DNMTs) catalyze methylation, and their functions in mammalian embryonic development diseases including cancer have been extensively studied. However, regulation of DNMTs remains under study. Here, we show that CCAAT/enhancer binding protein α (CEBPA) interacts with the long splice isoform DNMT3A, but not short DNMT3A2. CEBPA, by interacting DNMT3A N-terminus, blocks from accessing substrate thereby inhibits its activity. Recurrent tumor-associated CEBPA mutations,...
The innate immune response contributes to the development or attenuation of acute and chronic diseases, including cancer. Microbial DNA mislocalized from damaged host cells can activate different responses that shape disease outcomes. Here, we show mice humans lacking a single allele repair protein Ku70 had increased susceptibility intestinal Mechanistically, translocates nucleus into cytoplasm where it binds cytosolic interacts with GTPase Ras kinase Raf, forming tripartite complex docking...
Various types of mutation and editing (M/E) events in microRNAs (miRNAs) can change the stabilities pre-miRNAs and/or complementarities between miRNAs their targets. Small RNA (sRNA) high-throughput sequencing (HTS) profiles contain many mutated edited miRNAs. Systematic detection miRNA sites from huge volume sRNA HTS is computationally difficult, as high sensitivity low false positive rate (FPR) are both required. We propose a novel method (named MiRME) for an accurate fast M/E using...
Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR associated with numerous human diseases including several cancers. Despite consistent reports demonstrating that intrinsic sequence features can help introns evade splicing, conflicting findings about cell type- or condition-specific regulation by trans-regulatory and epigenetic mechanisms demand an unbiased systematic analysis a controlled experimental setting. We integrated matched mRNA...
Key Points Foxp1 is a key transcriptional factor for the differentiation of intercalated cells in collecting ducts. Dmrt2 and Hmx2 act downstream to control type A B cells, respectively. are essential body acid–base balance regulation. Background Kidney ducts comprise principal with playing crucial role kidney regulation through H + HCO 3 − secretion. Despite its significance, molecular mechanisms controlling cell development remain incompletely understood. Methods To investigate specific...
Mouse kidney parvovirus (MKPV) is a member of the provisional genus Chapparvovirus that causes renal disease in immune-compromised mice, with course reminiscent polyomavirus-associated nephropathy immune-suppressed transplant patients. Here we map four major MKPV transcripts, created by alternative splicing, to common initiator region, and use mass spectrometry identify "p10" "p15" as novel chapparvovirus accessory proteins produced MKPV-infected kidneys. p15 splicing-dependent putative...
Background & AimsThe liver has complex interconnecting blood vessel and biliary networks; however, how the vascular network form regulate each other function are not well-understood. We aimed to examine role of Heg in mammalian development functional maintenance.MethodsGlobal (Heg-/-) or endothelial cell (EC)-specific deletion (Lyve1-Cre;Hegfl/fl ) mice were used study vivo liver. Carbon-ink anterograde retrograde injection visualize 3-dimensional patterning portal networks, respectively....
Abstract RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that regulate innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. While m 6 A has been widely studied, other modifications, including 5 hmC, remain poorly characterised. We profiled hmC epitranscriptomes, transcriptomes, translatomes proteomes monocytes macrophages at rest pro- anti-inflammatory states....
Gut microbiota has been shown to play an important role in the pathogenesis of liver injury and fibrosis, but specific microbial factors or pathways involved remain poorly defined. Here we show that gut metabolites, notably indole, activate cytochrome P450 (CYP) eicosanoid pathway protect against fibrosis. Using LC-MS/MS-based lipidomics compare conventionally raised mice with germ-free antibiotic-treated mice, induces CYP liver. Furthermore, by administering exogenous indole mono-colonizing...
Vascular smooth muscle cells (VSMCs) possess significant phenotypic plasticity, shifting between a contractile phenotype and synthetic state for vascular repair/remodelling. Dysregulated VSMC transformation, marked by excessive proliferation migration, primarily drives intimal hyperplasia. N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, plays critical role gene expression regulation; however, its impact on plasticity is not fully understood. This research...
Virilizer-like m6A methyltransferase-associated protein (VIRMA) maintains the stability of writer complex. Although VIRMA is critical for RNA deposition, impact aberrant expression in human diseases remains unclear. We show that amplified and overexpressed 15-20% breast cancers. Of two known isoforms, nuclear-enriched full-length but not cytoplasmic-localised N-terminal promotes m6A-dependent tumourigenesis vitro vivo. Mechanistically, we reveal overexpression upregulates m6A-modified long...
Human and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω-6), an essential fatty key component the human diet, increases risk colon cancer. However, results from have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given importance in is crucial better understand molecular mechanisms underlying its potential cancer-promoting effects. Using LC-MS/MS-based targeted lipidomics, we find cytochrome P450 (CYP)...
Abstract The aged brain is associated with an inevitable decline in cognitive function and increased vulnerability to neurodegenerative disorders. Multiple molecular hallmarks have been the aging nervous system through transcriptomics proteomic studies. Recently, epitranscriptomic analysis has highlighted role of RNA chemical modification various biological processes. In particular, N 6‐methyladenosine (m6A), most abundant internal eukaryotic mRNAs, functionally linked multiple aspects...
Abstract RNA modifications have emerged as central regulators of gene expression programs. Amongst are N6-methyladenosine (m 6 A) and 5-hydroxymethylcytosine (5hmC). While m A is established a versatile regulator metabolism, the functions 5hmC unclear. Despite some evidence linking to immunity, their implications in control macrophage development remain Here we present multi-omics dataset capturing different layers programs driving differentiation polarisation. We obtained mRNA-Seq,...
Altered expression profiles of microRNAs (miRNAs) are linked to many diseases including lung cancer. miRNA profiling is reproducible and miRNAs very stable. These characteristics make them ideal biomarker candidates. This work aimed detect 2-and 3-miRNA groups, together with specific ranges these miRNAs, form simple linear discriminant rules for identification biological interpretation. Our method based on a novel committee decision trees derive 100%-frequency rules. applied data set 61...
Abstract Monocytes play a crucial role in maintaining homeostasis and mediating successful innate immune response. They also act as central players diverse pathological conditions, thus making them an attractive therapeutic target. Within the bone marrow, monocytes arise from committed precursor termed Common Monocyte Progenitor (cMoP). However, molecular mechanisms that regulate differentiation of cMoP to various monocytic subsets remain unclear. Herein, we purified murine myeloid...
The epicardium provides epicardial-derived cells and molecular signals to support cardiac development regeneration. Zebrafish mouse studies have shown that ccm2, a cerebral cavernous malformation disease gene, is essential for development. Endocardial cell-specific deletion of Ccm2 in mice has previously established maintenance the jelly during early gestation. current study aimed explore function epicardial heart Through genetic cells, our vivo ex experiments revealed required by regulates...
Abstract Background and Aims Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk inflammatory bowel disease (IBD). PUFA highly prone to oxidation. To date, it unclear whether unoxidized or oxidized involved in the development IBD. Here, we aim compare effects vs on IBD colorectal cancer. Methods We evaluated dextran sodium sulfate (DSS)-induced IL-10 knockout-induced colitis, azoxymethane/DSS-induced colon tumorigenesis mice....
Summary Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR associated with numerous human diseases including cancer. Despite consistent reports demonstrating intrinsic sequence features that predispose introns to become retained, conflicting findings about cell type-specific regulation demand a systematic analysis controlled experimental setting. We integrated matched transcriptomics and epigenetics data (including DNA methylation,...