Biology subjects

Oh, R.

Publications and source records attributed to Oh, R..

3 recordsLinked to original sources

bioRxiv2022

Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability

Tumour suppressor p53 (TP53) is the most frequently mutated gene in cancer. Several hotspot p53 mutants not only lose tumour suppressive capabilities, but also function in a dominant-negative manner, suppressing canonical wild-type p53 function. Furthermore, some hotspot p53 mutants promote oncogenesis by gain-of-function mechanisms. Levels of p53 are regulated predominantly through regulation of protein stability and while wild-type p53 is normally kept at very low levels at steady-state, p53 mutants are often stabilized in tumours, which may be vital for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. We found that most proteins that regulate wild-type p53 also regulate a subset of p53 mutants with the exception of p53 R337H regulators, which are largely private to this mutant. Mechanistically, we identified FBXO42 as a novel positive regulator of a subset of p53 mutants comprising R273H, R248Q and R248W. We show that FBXO42 acts together with CCDC6 to regulate USP28-mediated p53 stabilization. Our work also identifies C16orf72 as a negative regulator of the stability of wild-type p53 and of all p53 mutants tested. C16orf72 is amplified in breast cancer, and we show that C16orf72 regulates p53 levels in mammary epithelium of mice and its overexpression results in accelerated breast cancer with reduced p53 levels. Together, this work provides a network view of the processes that regulate p53 stability, which might provide clues for reinforcing wild-type p53 or targeting mutant p53 in cancer.

cancer biology↗

bioRxiv2021

Tapping into non-English-language science for the conservation of global biodiversity

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,680 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate, and can expand the geographical (by 12-25%) and taxonomic (by 5-32%) coverage of English-language evidence, especially in biodiverse regions, albeit often based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges.

scientific communication and education↗

bioRxiv2018

Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and upregulation of reactive oxygen species in non-small-cell lung cancer cells

BackgroundCalotropis gigantea (CG) plant grows in Asia and tropical Africa. However, the precise mechanisms of its anticancer effects have not yet been examined in human non-small cell lung cancer (NSCLC) cells, A549 and NCI-H1299 cells.\n\nPurposeThis study was focused on the anti-cancer effects of CG extract on non-small cell lung cancer (NSCLC) cells.\n\nMethodsThe cytotoxic effects of CG extract on NSCLC, A549 and NCI-H1299 cells, were detected by MTS assay, microscope and DAPI staining. Apoptosis was determined by annexin V-FITC/PI staining, cell cycle analysis, western blotting, quantitative polymerase chain reaction, and JC-1 staining.\n\nResultsFirst, CG showed significant dose-dependent cytotoxicity in NSCLC, A549, and NCI-H1299 cells. In addition to induction of caspase-8 processing, CG induced apoptosis by upregulating mRNA expression levels of extrinsic pathway molecules such as Fas, Fas ligand (FasL), Fas-associated protein with death domain (FADD) and death receptor 5 (DR5). Also, mitochondrial membrane potential (MMP) was collapsed, and intrinsic pathway molecules such as poly (ADP-ribose) polymerase (PARP), caspase-3, and caspase-9 were processed by CG. Moreover, reactive oxygen species (ROS) were generated in a CG dose-dependent manner, and inhibition of ROS by NAC, ROS scavenger, recovered A549 and NCI-H1299 cell viability.\n\nConclusionThese results indicate that CG causes apoptosis by activating the extrinsic and intrinsic pathways and generating ROS in NSCLC cells. These results suggest that CG can be used as a lung cancer therapeutic agent.

cancer biology↗