Biomedical subjects

Qian Xiao

Publications and source records attributed to Qian Xiao.

3 recordsLinked to original sources

PubMed2026

ADCY2 promoter hypomethylation in adolescents with borderline personality disorder: An RRBS study with targeted BSP replication.

BACKGROUND: Borderline Personality Disorder (BPD) is characterized by emotional dysregulation, impulsivity, and interpersonal instability. Although genetic and environmental contributions to BPD have been investigated, epigenetic correlates in adolescents remain poorly understood. The cyclic adenosine monophosphate (cAMP) signaling pathway is implicated in stress responsivity and emotion regulation, but its epigenetic variation in adolescent BPD remains understudied. METHODS: DNA methylation profiling was performed using Reduced Representation Bisulfite Sequencing (RRBS) in buccal epithelial DNA from adolescents with BPD (n = 15) and healthy controls (HC; n = 15). Differentially methylated regions (DMRs) were identified using metilene, a computational tool for detecting DMRs from bisulfite sequencing data, and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Associations between methylation signals and borderline personality features were examined. Adenylate cyclase 2 (ADCY2) promoter methylation was examined using targeted bisulfite sequencing PCR (BSP) in an independent cohort (BPD n = 5; HC n = 5). RESULTS: RRBS identified 7641 DMRs between BPD and HC, with enrichment in pathways related to neuronal signaling and synaptic organization. A hypomethylated DMR was detected in the ADCY2 promoter, a gene implicated in cAMP signaling. Lower ADCY2 promoter methylation was associated with greater clinical severity, including emotional dysregulation, borderline traits, anxiety symptoms, and self-injury behaviors (r=-0.71 to -0.83; all p < 0.0001). Hypomethylation of the ADCY2 promoter was replicated in the independent cohort. CONCLUSIONS: This exploratory two-stage epigenetic study suggests that ADCY2 promoter hypomethylation in peripheral buccal epithelial DNA is associated with core symptom dimensions of adolescent BPD. These findings support a role for cAMP-related epigenetic variation in BPD and warrant replication in longitudinal studies.

ADCY2↗

PubMed2026

Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy.

The liver undergoes active remodeling by the primary tumor prior to metastatic spread. However, the mechanisms by which hepatocytes dictate the liver-specific tropism of tumors remain elusive. Here, we identify hepatocyte-derived leucine-rich alpha-2-glycoprotein 1 (LRG1) as a key mediator of liver premetastatic niche (PMN) formation. Clinically, elevated serum LRG1 levels are correlated with an increased risk of liver metastasis in patients and multiple mouse models. Mechanistically, LRG1 remodels the hepatic microenvironment by driving immunosuppressive neutrophil accumulation, impairing the function of effector T cells and dendritic cells, and enhancing angiogenesis in the liver, thereby fostering a prometastatic landscape. Hepatocyte-specific ablation of LRG1 dampens premetastatic niche formation and significantly reduces the metastatic burden in vivo. Hepatic LRG1 induced by tumor-associated inflammation via IL-6/STAT3 signaling promotes liver metastasis through the formation of TGFBR/PI3K/AKT axis-driven neutrophil extracellular traps (NETs). Importantly, therapeutic blockade of LRG1 not only suppressed liver metastasis but also reprogrammed the hepatic niche toward an immune-activated state, sensitizing tumors to anti-PD-1 therapy. Collectively, our findings reveal a hepatocyte-LRG1 axis that drives liver premetastatic niche remodeling and highlight LRG1 as a promising target for the prevention and treatment of liver metastasis.

Animals↗

PubMed2025

Systematic decoding of functional enhancer connectomes and risk variants in human glioma.

Genetic and epigenetic variations contribute to the progression of glioma, but the mechanisms underlying these effects, particularly for enhancer-associated genetic variations in non-coding regions, still remain unclear. Here we performed high-throughput CRISPR interference screening to identify pro-tumour enhancers in glioma cells. By integrating genome-wide H3K27ac HiChIP data, we identified the target genes of these pro-tumour enhancers and revealed the essential role of enhancer connectomes in promoting glioma progression. Through systematic analysis of enhancers carrying glioma risk-associated single-nucleotide polymorphisms (SNPs), we found that these SNPs can promote glioma progression through the enhancer connectome. Using CRISPR-Cas9-mediated enhancer interference and SNP editing, we demonstrated that glioma-specific enhancer carrying the risk SNP rs2297440 regulates SOX18 expression by specifically recruiting transcription factor MEIS1 binding, thereby contributing to glioma progression. Our study sheds light on the molecular mechanisms underlying glioma susceptibility and provides potential therapeutic targets to treat glioma.

Humans↗