Biology subjects

Wang, J.-M.

Publications and source records attributed to Wang, J.-M..

6 recordsLinked to original sources

bioRxiv2025

SELEX-HTCFQ Platform: Developing DNA Enhancers of ADAR1 to Suppress ZBP1-Dependent Immunopathology

Excessive immune activation drives pathological inflammation through dysregulated ZBP1 signaling, yet this sensor remains crucial for immune surveillance, necessitating targeted therapies that selectively inhibit pathology while preserving protective functions. Here, we developed an innovative SELEX-HTCFQ platform that combines Systematic Evolution of Ligands by Exponential Enrichment (SELEX) with high-throughput competitive fluorescence quenching (HTCFQ) to identify ADAR1-specific enhancers. Capitalizing on ADAR1s natural ability to suppress ZBP1 via competitive Z-nucleic acid binding, this platforms dual assessment of affinity and selectivity identified aptamer A4, a highly specific ADAR1 enhancers demonstrating over 40-fold selectivity over ZBP1. A4 allosterically modulates ADAR1s activity, thereby potentiating its inhibitory effect on ZBP1, which not only mitigates the excessive inflammatory response but also maintains the delicate balance of the immune system. These ADAR1 enhancers represent precision molecular tools for reprogramming Z-nucleic acid sensing, offering a promising therapeutic paradigm for cytokine storm syndromes and necroptosis-driven disorders through selective pathway modulation.

biochemistry↗

bioRxiv2023

Inhibition of miR-199b-5p reduces pathological alterations in Osteoarthritis by targeting Fzd6 and Gcnt2

Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miRNA-199b-5p. In vitro cell experiments demonstrated that miRNA-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miRNA-199b-5p under inflammatory conditions exhibited protective effects against damage. Local viral injection of miRNA-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miRNA-199b-5p alleviated the pathological progression of OA. Furthermore, bioinformatics analysis and experimental validation identified Gcnt2 and Fzd6 as potential target genes of miRNA-199b-5p. Thus, these results indicated that miRNA-199b-5p/Gcnt2 and Fzd6 axis might be a novel therapeutic target for the treatment of OA.

molecular biology↗

bioRxiv2021

Characterization of epigenetic alterations in esophageal cancer by whole-genome bisulfite sequencing

Esophageal carcinoma is a common and aggressive malignancy, and its patients have dismal clinical outcomes. The epigenetic dysregulation in both major subtypes, esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), awaits further characterization. Here, we perform whole-genome bisulfite sequencing (WGBS) on a total of 43 esophageal cancer and normal samples, generating one of the largest WGBS datasets in this cancer to date. Focusing on hypomethylated regions in cancer, we show that they are associated with increased chromatin activity and enhancer RNA expression. Using this large collection of WGBS dataset, we reveal and validate novel clusters in both ESCC and EAC. We further identify specific molecular features in each cluster, with potential clinical implications. These data together advance our understanding of the epigenetic alterations in esophageal cancer and provide a rich resource for the research community of this disease.

cancer biology↗

bioRxiv2019

Insulin signal transduction is impaired in the type 2 diabetic retina

Rates of type 2 diabetes are reaching epidemic levels. Yet, the tissue specific alterations due to insulin resistance are only recently being investigated. The goal of the present study was to evaluate retinal insulin signal transduction in a common mouse model of type 2 diabetes, the db/db mouse. Retinal lysates from five month old male db/db and db/+ (control) mice were collected and processed for Western blotting or ELISA analyses for insulin receptor, insulin receptor substrate-1 (IRS-1), Akt, tumor necrosis factor alpha (TNF) and caspase 3 levels. Data demonstrate increased TNF and IRS-1 phosphorylation on serine 307. This led to decreased Akt phosphorylation on serine 473 and increased cleavage of caspase 3. Taken together, the data suggest dysfunctional insulin signaling in the retina of the db/db mouse.

cell biology↗

bioRxiv2018

HBx enhances CPAP expression via interacting with CREB to promote hepatocarcinogenesis in HBV-associated HCC

Hepatitis B virus (HBV) encoded non-structure protein X (HBx) can promote cell proliferation, migration, and anti-apoptosis via activating several transcription factors and increasing their downstream gene expression in HBV-infected liver cells. Our previous report suggested that centrosomal P4.1-associated protein (CPAP) is required for HBx-mediated NF-{kappa}B activation. Here, we found that, upon HBV infection, overexpressed HBx can transcriptionally up-regulate CPAP via interacting with CREB. CPAP can directly interact with HBx to promote HBx-mediated cell proliferation and migration; and SUMO modification of CPAP is involved in interacting with HBx. Interestingly, CPAP can increase the HBx protein stability in an NF-{kappa}B-dependent manner; and overexpressed CPAP and HBx is positively correlated with the activation status of NF-{kappa}B in HCC. Increased expression of CREB and CPAP mRNAs exists in the high-risk group with a lower survival rate in hepatocellular carcinoma (HCC). These results suggest that the reciprocal regulation between CPAP and HBx may provide a microenvironment to facilitate HCC development via enhancing NF-{kappa}B activation, inflammatory cytokine production, and cancer maligancies. The findings of this study not only shed light on the role of CPAP in HBV-associated HCC, but also provide CPAP as a potential target for HBV-related HCC therapy.\n\nAuthor SummaryIn this study, we address a novel molecular mechanism for the collaboration between overexpressed HBx and CPAP in promoting hepatocarcinogenesis in HBV-associated HCC. Upon HBV infection, HBx is overexpressed and interacts with CREB to transcriptionally activate CPAP; the HBx/CPAP interaction promotes hepatocarcinogenesis. Clinical analysis found that co-overexpressed CPAP and CREB exist in the high-risk group with a lower survival rate in HCC. Additionally, overexpressed CPAP contributes to HBx protein stability in a NF-{kappa}B-dependent pathway. Our study provides a potential translational application in targeting CREB-CPAP axis in HBV-associated HCC.

cancer biology↗

bioRxiv2018

HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer

Pancreatic cancer is refractory and characterized by extensively surrounding- and intra-tumor fibrotic reactions that are contributed by activated pancreatic stellate cells (PSCs). Activation of PSCs plays a pivotal role for developing fibrotic reactions to affect themselves or pancreatic cancer cells (PCCs). In the current study, we demonstrated that hepatoma-derived growth factor (HDGF) was secreted from transforming growth factor-{beta}1 (TGF-{beta}1)-treated PSCs. We found that HDGF contributed to anti-apoptosis of PSCs and led to synthesis and depositions of extracellular matrix proteins for stabilizing PSCs/PCCs tumor foci. CCAAT/enhancer binding protein {delta} (CEBPD) responds to TGF-{beta}1 through a reciprocal loop regulation and further activated hypoxia inducible factor-1 (HIF-1) contributed to up-regulation of HDGF gene. It agrees with the observation that severe stromal growth positively correlated with stromal HDGF and CEBPD in pancreatic cancer specimens. Collectively, the identification of TGF-{beta}1-activated CEBPD/HIF-1/HDGF axis provides new insights for the novel discoveries of HDGF in anti-apoptosis and pro-fibrosis of PSCs and outgrowth of pancreatic cancer cells.

cancer biology↗