Biomedical subjects

Qian Guo

Publications and source records attributed to Qian Guo.

3 recordsLinked to original sources

PubMed2026

RHAMM drives formation of polyploid cancer cells and confers resistance to ER-targeted therapy in breast cancer.

Endocrine resistance in ER+ breast cancer remains a major clinical challenge. Here, we identify RHAMM as a key driver of resistance by orchestrating polyploid cancer cell (PCC) formation. Single-cell transcriptomics uncovered a G2/M-enriched, RHAMM+ subpopulation in endocrine-resistant tumors. Mechanistically, RHAMM binds Septin9/10 to promote aberrant cytoskeleton polymerization, activating YAP independent of Hippo signaling, which induces cytokinesis failure and facilitates PCC generation. Concurrently, RHAMM destabilizes p21 mRNA, enabling cell cycle progression despite genomic instability. The RHAMM-p21 axis serves as a bypass mechanism supporting polyploidization. Upon endocrine treatment, RHAMM is transcriptionally up-regulated by Slug. Clinically, RHAMMhigh signatures are enriched in metastatic and recurrent ER+ tumors and correlate with poor prognosis, highlighting its therapeutic relevance. Importantly, targeting RHAMM or YAP abrogates PCC formation and restores fulvestrant sensitivity. These findings reveal RHAMM-mediated polyploidization as an adaptive mechanism underlying endocrine resistance, suggesting the therapeutic potential of targeting the RHAMM-YAP axis.

Humans↗

PubMed2026

Decoding tumor immune microenvironment heterogeneity by single-cell and spatial multi-omics: From immunotherapy resistance to translational biomarkers.

Immune checkpoint blockade has transformed cancer therapy, yet primary and acquired resistance remain major clinical challenges. Increasing evidence indicates that immunotherapy resistance cannot be fully explained by tumor-intrinsic alterations or conventional biomarkers such as PD-L1 expression, tumor mutational burden, or microsatellite instability. Instead, therapeutic response is shaped by the tumor immune microenvironment (TIME) as a heterogeneous, spatially organized, and dynamically evolving ecosystem. Single-cell omics has revealed diverse immune and stromal cell states, including progenitor and terminally exhausted T cells, suppressive myeloid programs, B-cell/TLS-associated immune-reactive states, and CAF-mediated exclusion phenotypes. Spatial transcriptomics, spatial proteomics, and imaging-based approaches further demonstrate that these cell states assemble into distinct immune niches, including immune-inflamed, T-cell-excluded, myeloid-suppressive, metabolic/hypoxic, and TLS-associated niches. These spatial ecosystems determine whether antitumor immune cells can access malignant cells, receive antigen-presenting support, or become restrained by stromal, vascular, metabolic, and myeloid barriers. In this review, we summarize how single-cell and spatial multi-omics redefine TIME heterogeneity in immunotherapy resistance, highlight ligand-receptor communication networks linking cell states to spatial immune dysfunction, and discuss emerging translational biomarkers for patient stratification. We further propose that future immunotherapy biomarkers should evolve from static single-marker assays toward longitudinal, spatially resolved, and interpretable multi-omics models that guide precision combination immunotherapy.

Humans↗

PubMed2026

One Plasmid Is All You Need: Genome Editing in Escherichia coli Using Endogenous TnpB and Endogenous Recombination System.

Escherichia coli (E. coli) is a key workhorse of biotechnology. Commonly used CRISPR-Cas9 systems for E. coli genome editing are complex and impose metabolic stress on the host, creating demand for more streamlined strategies. Recent studies identified the IS605 transposon-associated TnpB as a programmable RNA-guided (ωRNA) DNA endonuclease, prompting us to explore whether endogenous TnpB in E. coli (EcoTnpB) could be harnessed for genome editing. Biochemical and cellular analyses demonstrated that EcoTnpB efficiently cleaves both chromosomal and plasmid DNA at custom-specified sites in a TAM-dependent manner. Interestingly, E. coli possesses an endogenous recombination machinery capable of repairing EcoTnpB-induced DNA double-strand breaks (DSBs), challenging the long-held view that bacteria lack efficient homologous recombination systems. Based on these findings, we established a single-plasmid editing system (SPEED) in which genome editing is achieved by simply providing ωRNA and a homologous recombination template. By utilizing endogenous EcoTnpB together with the host HR pathway, this system enabled inducible and seamless genome editing at multiple genomic loci in BL21 (DE3), with editing efficiencies ranging from approximately 29% to 56%. Our results demonstrate for the first time that endogenous TnpB can be harnessed for genome editing and may hold potential for broader applications, such as species-specific antimicrobial development.

Escherichia coli↗