Biology subjects

xu, w.

Publications and source records attributed to xu, w..

3 recordsLinked to original sources

bioRxiv2024

RFX6 at locus 6q22 confers metastasis and drug resistance in prostate cancer

Genetic and nonmutational epigenetic alterations are cancer hallmark characteristics. However, the role of inherited cancer predisposition alleles in co-opting lineage factor epigenetic reprogramming and contributing to tumor progression remains elusive. Here the FinnGen cohort phenome-wide analysis, along with recent multiple genome-wide association studies, has consistently identified the rs339331-RFX6/6q22 locus associated with prostate cancer (PCa) risk across diverse populations. We uncover that rs339331 resides at a reprogrammed androgen receptor (AR) binding site in PCa tumors, with the T risk allele enhancing AR chromatin occupancy under androgen signaling. We establish that RFX6 is an AR-regulated gene, intricately linked with rs339331, exhibiting synergistic prognostic value for PCa recurrence and metastasis. Through comprehensive in vitro and in vivo studies, we establish the oncogenic functions of RFX6 in promoting PCa cell proliferation and metastasis. Mechanistically, RFX6 upregulates transcription factor HOXA10 that profoundly correlates with adverse PCa outcomes and is pivotal in RFX6-mediated PCa progression, facilitating the epithelial-mesenchymal transition (EMT) process and modulating the TGF{beta}/SMAD signaling axis. Clinically, HOXA10 elevation is associated with increased EMT scores, tumor advancement and PCa recurrence. Remarkably, reducing RFX6 expression restores responsiveness of enzalutamide-resistant PCa cells and tumors to treatment. Our study highlights an interplay of disrupted genetic and epigenetic mechanisms converging on prostate lineage AR signaling, resulting in abnormal expression of RFX6 conferring PCa pathogenesis and enzalutamide resistance.

cancer biology↗

bioRxiv2022

Novel Viroid-like RNAs Naturally Infect a Filamentous Fungus

Viroids have been found to naturally infect only plants, resulting in big losses for some crops, but whether viroids or viroid-like RNAs naturally infect non-plant hosts remains unknown. Here we report the existence of a set of exogenous, single-stranded circular RNAs, ranging in size between 157-450 nucleotides (nt), isolated from the fungus Botryosphaeria dothidea and nominated Botryosphaeria dothidea circular RNAs (BdcRNAs). BdcRNA(s) replicate autonomously in the nucleus via a rolling-circle replication mechanism following symmetric pathways with distribution patterns depending on strand polarity and species. BdcRNAs can modulate to different degrees specific biological traits (e.g., alter morphology, decrease growth rate, attenuate virulence, and increase or decrease tolerance to osmotic stress and oxidative stress) of the host fungus by regulating related metabolic pathways. Overall, BdcRNA(s) have genome characteristics similar to those of viroids and exhibit pathogenic effects on the fungal hosts. These novel viroid-like RNAs infecting fungi are proposed to be termed as mycoviroids. BdcRNA(s) may be regarded as additional inhabitants at the frontier of life in terms of genomic complexity, and represent a new class of acellular entities endowed with regulatory functions, and novel epigenomic carriers of biological information. Significance statementSeveral viroids have been transfected into unicellular and filamentous fungi to assess whether they can replicate, but no natural infections of fungi with viroid or viroid-like RNAs have been reported before. Here we describe a set of exogenous circular RNAs (cRNAs) in a phytopathogenic fungus. These cRNAs display molecular and biological features which might represent a new class of viroid-like cRNAs endowed with regulatory functions, and novel epigenomic carriers of biological information. This is the first report of infectious viroid-like RNAs (or exogenous small cRNAs) in a life kingdom (fungi) other than plants. We also present a subcellular analysis of cRNAs in a fungus for the first time and provide useful understanding in how cRNAs replicate, move, and are distributed in fungal cells.

microbiology↗

bioRxiv2021

Deep Learning Genome-wide Linkage Association Study for Wheat Fusarium Head Blight Resistance Genes Discovery

BackgroundFusarium head blight (FHB) is one of the most devastating diseases of wheat worldwide and artificial intelligence can assist with understanding resistance to the disease. Considering different sample populations, marker types, reference maps, and statistical methods, we developed a Deep Learning Genome-wide Linkage Association Study (dpGLAS) of FHB resistance in wheat. ResultsThe dpGLAS was first applied to two bi-parental population datasets in which the cultivar AC Barrie was a common parent for FHB resistance. Eight candidate gene markers were discovered in the one AC Barrie population and 10 in the other associated with FHB resistance. Eight of these markers were also supported by the conventional QTL mapping. Most of these candidate marker genes were found associated with the Reactive Oxygen Species (ROS) and Abscisic acid (ABA) axes. These ROS and ABA pathways were further supported by RNA-seq transcriptome data of FHB resistant cv. AAC Tenacious, a parent of the third bi-parental population. In this dataset, the ROS-centered Panther protein families were significantly enriched in those genes that had most different response to FHB when compared the resistance Tenacious and the susceptible Roblin. ConclusionsThis study developed the framework of dpGLAS and identified candidate genes for FHB resistance in the Canadian spring wheat cultivars AC Barrie and AAC Tenacious.

bioinformatics↗