Biology subjects

CHANG, Y.

Publications and source records attributed to CHANG, Y..

3 recordsLinked to original sources

bioRxiv2026

CBX3 Deletion Overcomes Ferroptosis Resistance in Colorectal Cancer by Targeting IFNγ/SLC7A11/SLC3A2 Axis

System Xc- (SLC7A11/SLC3A2) maintains redox balance by supporting glutathione synthesis, thereby preventing lipid peroxidation and ferroptosis, and represents a promising therapeutic target in cancer. In this work, we revealed that an important epigenetic regulator, CBX3 deletion significantly increased intracellular ROS and lipid ROS level following ferroptosis inducing, particularly under IFN{gamma} stimulation, thereby sensitized CRC cells to ferroptosis in vitro using human CRC cells as well as in vivo using MC38 syngenetic tumors. RNAseq with mice syngeneic tumors revealed an 11-gene oxidative stress signature downregulated in Cbx3KO tumors after combined treatment; its low expression score correlated with improved overall survival in CRC patients. Among them, Slc7a11, Ptgs2, and Cth were identified as CBX3 direct target genes. Additionally, several amino acid transporters functionally coupled to Xc- antiporter, as Slc3a2, Slc7a5, Slc1a5 and Slc6a9, all significantly decreased in Cbx3KO tumor under RSL3+IFN{gamma} treatment. Mechanistically, CBX3 binds directly to the promoter of Slc7a11 or Slc3a2 to sustain their expression and redox balance to resist ferroptosis in CRC. Knockout of CBX3 in CRC cells significantly impaired RNA polymerase II recruitment to the promoter of SLC7A11 or SLC3A2 and reduced SLC7A11 and SLC3A2 expression, an effect that was further exacerbated under IFN{gamma} stimulation but restored by STAT1 deletion. Overall, CBX3 protects CRC from oxidative stress by maintaining the functional integrity of IFN{gamma}/STAT1/SLC7A11/SLC3A2 axis, positioning CBX3 as a potential therapeutic target for enhancing ferroptosis therapies in CRC.

cancer biology↗

bioRxiv2026

An active-matrix digital microfluidic platform for simultaneous short- and long-read viral genomic surveillance

The outbreak frequency and geographic distribution of viral pathogens are continuously expanding, making enhanced genomic surveillance an urgent global public health need. Parallel library preparation combining next-generation sequencing (NGS) and third-generation sequencing (TGS) can substantially improve the coverage and resolution of genomic surveillance, representing a key strategy for strengthening surveillance. Here we developed a complete sample-to-result system integrating a programmable active-matrix digital microfluidic (AM-DMF) chip with a bioinformatics analysis pipeline. Compared with conventional manual protocols used in public health laboratories, our system reduces reagent consumption by 72%, shortens library preparation time by 45% and decreases the inter-batch coefficient of variation (CV) by 20%. In 20 RT-qPCR-confirmed clinical samples, the system achieved complete concordance for viral identification and assigned serotypes/genotypes consistent with sequencing-based phylogenetic analysis. This system is field-deployable and enables rapid virus serotyping as well as in-depth genomic surveillance. TeaserA digital microfluidic platform integrating short- and long-read sequencing enables rapid comprehensive viral genome analysis.

bioengineering↗

bioRxiv2020

A Novel Regulatory Role for the Circadian Clock Protein TOC1 via RNA binding

The circadian clock enables plants to predict daily changes of external signals and synchronize them with internal processes, conferring enhanced fitness and growth vigor. The first described Arabidopsis circadian clock protein is TIMING OF CAB EXPRESSION 1 (TOC1), which functions in a transcriptional feedback loop with two myb transcription factors, CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Previous studies have shown that TOC1 is a DNA-binding transcriptional repressor of CCA1 and LHY. However, the DNA motifs enriched amongst TOC1 targets share weak sequence similarity and lack consensus, suggesting that TOC1 regulates the expression of its targets through a novel mechanism. Here we show that the TOC1 protein binds directly to RNA via its conserved CCT domain. Using in vitro RNA selection, we identified an RNA motif that is recognized by the TOC1-CCT domain. The TOC1-CCT domain binds to this RNA sequence with nanomolar affinity determined by quantitative electrophoretic mobility shift assays (EMSAs) and isothermal titration calorimetry (ITC). NMR experiments showed that two CCT fragments, CCT533-547 and CCT550-565, use basic residues to bind the RNA motif. Mutational analysis confirmed that lysyl and arginyl residues bind to RNA in a cooperative manner. Furthermore, transiently expressed wildtype and mutant TOC1 in protoplasts demonstrated that RNA binding activity of TOC1 is required for its function as a transcriptional repressor in vivo. Our results reveal a novel regulatory mechanism for TOC1 through RNA binding, suggesting that TOC1 might play key roles as a multi-function protein.

plant biology↗