ORCID Profile
0000-0002-4471-9768
Current Organisation
University of South Australia
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Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.CELL.2015.02.014
Abstract: Circular RNAs (circRNAs), formed by non-sequential back-splicing of pre-mRNA transcripts, are a widespread form of non-coding RNA in animal cells. However, it is unclear whether the majority of circRNAs represent splicing by-products without function or are produced in a regulated manner to carry out specific cellular functions. We show that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and find that the production of over one-third of abundant circRNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT. Furthermore, by modulating QKI levels, we show the effect on circRNA abundance is dependent on intronic QKI binding motifs. Critically, the addition of QKI motifs is sufficient to induce de novo circRNA formation from transcripts that are normally linearly spliced. These findings demonstrate circRNAs are both purposefully synthesized and regulated by cell-type specific mechanisms, suggesting they play specific biological roles in EMT.
Publisher: EMBO
Date: 06-06-2018
Publisher: MDPI AG
Date: 04-11-2021
Abstract: Urine-based biomarkers have shown suitable diagnostic potential for prostate cancer (PCa) detection. Yet, until now, prostatic massage remains required prior to urine s ling. Here, we test a potential diagnostic approach using voided urine collected without prior digital rectal examination (DRE). In this study, we evaluated the diagnostic performance of a microfluidic-based platform that combines the principle of photodynamic diagnostic with immunocapture for the detection of PCa cells. The functionality and sensitivity of this platform were validated using both cultured cells and PCa patient urine s les. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) demonstrated this platform had a detection limit of fewer than 10 cells per 60 µL and successfully validated the presence of a PCa biomarker in the urine of cancer patients without prior DRE. This biosensing platform exhibits a sensitivity of 72.4% and a specificity of 71.4%, in suitable agreement with qRT-PCR data. The results of this study constitute a stepping stone in the future development of noninvasive prostate cancer diagnostic technologies that do not require DRE.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.ABB.2019.108169
Abstract: Pyruvate carboxylase (PC) is a biotin-containing enzyme that converts pyruvate to oxaloacetate. We have previously shown that PC is overexpressed in highly invasive cancer cell lines where it supports biosynthesis during rapid cell growth. Here, we show that miR-143-3p suppresses the expression of PC in MDA-MB-231 cells by targeting its conserved binding site in the 3'-untranslated region (UTR) of human PC mRNA. Incorporation of the PC 3'UTR into a luciferase reporter gene inhibited expression of luciferase by 50% while mutation of the miR-143-3p binding site abrogated this inhibitory effect in MDA-MB-231 cells but not in low aggressive MCF-7 cell line. Transfection of miR-143-3p mimic or overexpression of miR-143-3p using tetracycline-inducible system in MDA-MB-231 cells down-regulated expression of both endogenous PC mRNA and protein by 40% and 50% respectively, confirming the regulatory role of miR-143-3p in PC expression. Induction of miR-143-3p expression at low and high levels lowered proliferation, metabolic activity and migration of MDA-MB-231 cells, in a dose-dependent manner. Re-expression of PC in MDA-MB-231 cells which were induced to express miR-143-3p partially restored migration but not proliferation, indicating that miR-143-3p regulates proliferation and migration through multiple pathways.
No related grants have been discovered for Caroline Phillips.