Biomedical subjects

Xun Wang

Publications and source records attributed to Xun Wang.

4 recordsLinked to original sources

PubMed2026

Loss of PBRM1 accelerates pancreatic cancer progression by inducing acquisition of mesenchymal phenotype and inflammatory cancer-associated fibroblasts reprogramming.

BACKGROUND: PBRM1 is an important subunit of the SWI/SNF complex, which broadly regulates gene transcription by chromatin remodeling. Genomic alterations of PBRM1 have been found in patients with pancreatic ductal adenocarcinoma (PDAC), but its molecular functions remain unclear. METHODS: Clinical relevance of PBRM1 was analyzed by using human PDAC samples and public genomic datasets. Mice with concomitant pancreas-specific Pbrm1 deletion in Kras-driven genetic PDAC models were generated. Single-cell transcriptomics were performed to determine tumor phenotype and microenvironment reprogramming. RESULTS: Reduction of PBRM1 expression was observed in human PDAC tissues and correlated with poor prognosis and metastasis. Pbrm1 loss promoted ductal metaplasia and delayed epithelial recovery in mice with caerulein-induced pancreatic injury. In PDAC model with either mutant Kras alone or in combination with Trp53 mutation, lack of Pbrm1 markedly accelerated tumor development and progression. Bulk transcriptomics and scRNA-seq identified reprogramming of both tumor compartment with mesenchymal phenotype acquisition and stroma compartment with inflammatory cancer-associated fibroblasts (iCAFs) transformation. Mechanistically, Pbrm1 deletion induced Zeb1 upregulation through epigenetic chromatin remodeling, thereby enhancing epithelial-mesenchymal and basal-like subtype transition. CONCLUSIONS: These findings indicated a tumor-suppressing role of PBRM1 in PDAC. PBRM1-deficient PDAC constitutes a specific subgroup of patients with aggressive phenotype and prognostic significance.

Animals↗

PubMed2026

Metagenomic insights into microbial drivers of organic micropollutant removal in wastewater-impacted riverbank filtration.

Organic micropollutants (OMPs) in wastewater treatment plant (WWTP) effluent pose persistent risks to aquatic ecosystems and drinking water sources. Riverbank filtration (RBF) is a nature-based treatment process, yet the compartment-specific roles of riverbed sediment and downstream soil in OMP attenuation remain poorly resolved under wastewater-impacted conditions. Here, we combined targeted chemical analysis, OMP property compilation, shotgun metagenomics, EnviPath-based biotransformation annotation, and exploratory network analysis to investigate OMP attenuation in a laboratory-scale RBF system treating real WWTP effluent for 10 months. Nineteen OMPs were monitored along a sequential sediment-soil filtration pathway. Sediment preferentially attenuated hydrophilic or charged compounds, including lidocaine, amantadine, and sotalol, whereas soil contributed more strongly to the attenuation of naproxen, atenolol, and losartan. Metagenomic profiling revealed distinct microbial communities and functional gene repertoires between sediment and soil after long-term operation. Sediment harbored higher relative abundances of genes associated with oxidative xenobiotic transformation, including cytochrome P450-related enzymes, demethylases, dehydrogenases, oxidases, and aromatic compound degradation pathways. An exploratory Spearman network further identified associations among microbial genera, EnviPath-annotated candidate biotransformation genes, and OMP removal rates, including 17 KO-OMP links supported by both correlation and pathway annotation. These findings indicate that sediment and soil develop complementary microbial functional potentials that may support compound-specific OMP attenuation. This study provides a mechanistic basis for optimizing sediment-soil configurations in wastewater-impacted RBF systems and for improving nature-based barriers against diverse OMP mixtures.

Wastewater↗

PubMed2025

Rho-dependent termination and RNase E-mediated cleavage: dual pathways for RNA 3' end processing in polycistronic mRNA.

"Pre-full-length" transcripts are produced at the end of the polycistronic galactose (gal) operon, 5' galE-galT-galK-galM 3', via Rho-dependent transcription termination (RDT) and -independent transcription termination. The 3' end of the full-length galETKM mRNA is acquired by exonucleolytic processing of the 3'-OH ends of the pre-full-length transcripts. However, the gal operon produces an mRNA termed galE whose 3' end forms approximately 120 nucleotides downstream of the galE stop codon, within the subsequent gene, galT, thereby establishing polarity in gene expression. In this study, we investigated the molecular processes that generate the 3' end of galE mRNA. We discovered that the 3' ends of pre-galE mRNA are produced in the middle of galT as a result of the combination of two separate molecular processes-one previously reported as RDT and the other as unreported RNase E-mediated transcript cleavage. The 3' ends of pre-galE mRNA undergo exonucleolytic processing to the 3' end of galE mRNA observed in vivo. A hairpin structure containing an 8 bp stem and a 4-nucleotide loop, located 5-10 nucleotides upstream of the 3' ends of galE mRNA, blocks exoribonuclease digestion and renders transcript stability. These findings demonstrate that RNase E-contrary to its general role in mRNA degradation-produces RNA 3' ends that regulate polarity in gene expression.IMPORTANCEThis study reports the findings of two molecular mechanisms that generate the 3' ends of pre-galE mRNA in the gal operon, viz., Rho-dependent transcription termination and RNase E-mediated cleavage. These 3' ends are subsequently processed to produce stable galE mRNA with a hairpin structure that prevents exoribonuclease degradation. This mechanism establishes gene expression polarity by generating the 3' end of galE mRNA within galT in contrast to the usual mRNA degradation role of RNase E. The study reveals a unique role of RNase E in mRNA processing and stability.

RNA, Messenger↗

PubMed2024

Reducing competition between msd and genomic DNA improves retron editing efficiency.

Retrons, found in bacteria and used for defense against phages, generate a unique molecule known as multicopy single-stranded DNA (msDNA). This msDNA mimics Okazaki fragments during DNA replication, making it a promising tool for targeted gene editing in prokaryotes. However, existing retron systems often exhibit suboptimal editing efficiency. Here, we identify the msd gene in Escherichia coli, which encodes the noncoding RNA template for msDNA synthesis and carries the homologous sequence of the target gene to be edited, as a critical bottleneck. Sequence homology causes the msDNA to bind to the msd gene, thereby reducing its efficiency in editing the target gene. To address this issue, we engineer a retron system that tailors msDNA to the leading strand of the plasmid containing the msd gene. This strategy minimizes msd gene editing and reduces competition with target genes, significantly increasing msDNA availability. Our optimized system achieves very high retron editing efficiency, enhancing performance and expanding the potential for in vivo techniques that rely on homologous DNA synthesis.

Gene Editing↗