https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37757 ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.]]> Wed 17 Nov 2021 16:28:34 AEDT ]]> LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50273 Wed 12 Jul 2023 14:18:12 AEST ]]> Skp2-mediated stabilization of MTH1 promotes survival of melanoma cells upon oxidative stress https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32181 Wed 09 Mar 2022 15:58:36 AEDT ]]> Cylindromatosis is required for survival of a subset of melanoma cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39074 Wed 04 May 2022 15:24:42 AEST ]]> The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51136 Tue 22 Aug 2023 15:58:29 AEST ]]> A p53-responsive miRNA network promotes cancer cell quiescence https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35745 chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment. Significance: Two novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize p27 to promote cell quiescence and may serve as therapeutic avenues for improving outcomes of cancer treatment.]]> Thu 28 Oct 2021 12:36:09 AEDT ]]> Visualization of endogenous p27 and Ki67 reveals the importance of a c-Myc-driven metabolic switch in promoting survival of quiescent cancer cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45318 Thu 27 Oct 2022 13:56:46 AEDT ]]> The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45314 Thu 27 Oct 2022 13:56:29 AEDT ]]> LncRNA REG1CP promotes tumorigenesis through an enhancer complex to recruit FANCJ helicase for REG3A transcription https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37758 regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA–DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.]]> Thu 27 Jan 2022 15:55:02 AEDT ]]> LncRNA MILIP links YBX1 to translational activation of Snai1 and promotes metastasis in clear cell renal cell carcinoma https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52635 Thu 19 Oct 2023 15:13:49 AEDT ]]> High nerve density in breast cancer is associated with poor patient outcome https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48186 Sat 11 Mar 2023 12:23:00 AEDT ]]> MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55358 Fri 17 May 2024 16:04:55 AEST ]]> KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55965 Fri 12 Jul 2024 13:48:32 AEST ]]>