Biology subjects

Na, R.

Publications and source records attributed to Na, R..

5 recordsLinked to original sources

bioRxiv2026

Streptococcal superantigen SpeC induces IL-8 secretion in human epithelial cells

Streptococcal pyrogenic exotoxin C (SpeC) is a prototypical superantigen produced by group A Streptococcus. It potently activates a broad subset of T lymphocytes via a bridging interaction involving TCR{beta}-SpeC-MHC-II. Our recent work demonstrated that SpeC induced profound release of IL-8 from human pharyngeal epithelial cells and this effect was reversible through a specific point mutation in SpeC. This study systematically investigated cellular signaling pathways using integrated transcriptomic profiling and Western blot analysis, with a focus on membrane-associated receptors and downstream intracellular signaling effectors. Our results demonstrate that this biological process is critically associated with the activation of Erk1/2, p38 MAPK and NF-{kappa}B signaling cascade. This study identifies a novel mechanism through which a bacterial superantigen target epithelial cells-the body primary physical barrier and first line of innate immune defense.

microbiology↗

bioRxiv2025

A unified eIF1A+ luminal cells-centered hypoxic and "cold" tumor microenvironment promotes PCa progression among different subtypes

PCa is a malignancy with high heterogeneity arises from both tumor microenvironment (TME) and histological subtypes. To achieve superior clinical efficacy, it is imperative to identify unified progression drivers within such heterogeneity in PCa, thereby enabling the development of more consistent and effective therapeutic strategies. In this study, we applied imaging mass cytometry to stain 39 proteins on 71 tissues comprising para-cancer, low-grade acinar adenocarcinoma (LgPAC), high-grade PAC (HgPAC), intraductal carcinoma (IDC) and ductal adenocarcinoma (DAC) tissues, obtaining the spatial proteomic landscape of 345,233 single cells. We discovered a hypoxic eIF1A+ luminal epithelial (LE) cluster exhibiting both translational activation and immunosuppressive properties, which was enriched in high-risk PCa including HgPAC, IDC and DAC, and associated which tumor progression and unfavorable prognosis. Additionally, eIF1A+ LE orchestrates the formation of an immunologically "cold" TME, characterized by the low infiltration of anti-cancer immune cells including PD1- T cells CD163- macrophages. Through in vivo validation and investigator-initiated study, we further found that Homoharringtonine, an inhibitor targeting protein translation process, effectively inhibited PCa growth, alleviated hypoxic microenvironment, and enhanced immune cell infiltration. This study is the first to apply spatial proteomics to delineate consistent molecular features across histological subtypes, providing transformative insights for clinical management of PCa.

cancer biology↗

bioRxiv2024

YY1 Enhances the Stability of HIF-1α Protein by Interacting with NUSAP1 in Macrophages within the Prostate Cancer Microenvironment

Immune checkpoint therapy for prostate cancer (PCa) has failed in clinical trials; however, the precise underlying mechanisms involved remain elusive. PCa, a classic "immune-cold" tumor, is characterized by an immunosuppressive tumor microenvironment. Within this milieu, macrophages, the predominant immune cell population, have a propensity to infiltrate the hypoxic zones of tumors. In a previous study, we showed that Yin Yang 1 (YY1) is highly expressed in macrophages in PCa tissues. Here, through multiplexed imaging mass cytometry (IMC) of a PCa tissue microarray, we further demonstrate that YY1+ macrophages aggregate in hypoxic areas of tumors and that hypoxia promotes the phase separation of YY1 in the nucleus by increasing YY1 tyrosine phosphorylation in macrophages. Furthermore, YY1 binds to NUSAP1 and promotes the SUMOylation of HIF-1, which promotes phase separation and stabilization of the HIF-1 protein. We also demonstrated that either treatment with a small molecule inhibitor (tenapanor) to decrease the YY1-NUSAP1-HIF-1 interaction or myeloid-specific YY1 gene knockout impairs subcutaneous PCa tumor formation. Furthermore, we present a first-generation tetrahedral DNA nanostructure (TDN) based on the proteolysis targeting chimera (PROTAC) technique, named YY1-DcTAC, which targets and degrades YY1 in tumor-associated macrophages. In a PCa mouse model, YY1-DcTAC exhibited prolonged drug efficacy, robust macrophage-specific responsiveness, potent antitumor effects, and increased CD8+ T cell tumor infiltration. In summary, our findings underscore the pivotal role of YY1 within the hypoxia/HIF-1 pathway in tumor-associated macrophages and affirm the therapeutic potential of targeting YY1 for treating PCa.

cancer biology↗

bioRxiv2019

A literature mining method to judge whether there are uncertaintiesin empirical-dependent antineoplastic drug distribution in specificclinical scenarios.

Cancer clinical practice guidelines recommend different treatment options for different cancer types and are mainly developed by clinicians. In theory, those recommendation schemes that are supported by scientific research should provide better efficacy for patients. However, in actual clinical practice: "Is the choice of a specific antineoplastic drug for a specific cancer supported by the results of molecular biology mechanisms or based on the subjective experience of the clinician?" Answering this question is of significant importance for guiding clinical practice, but there is currently no operational method to provide objective judgment in specific cases. This paper describes a literature mining method that collates information from specific antineoplastic drug-related literature to establish an antineoplastic drug-gene association matrix for global or specific cancer scenarios, and further establishes a standard model and scenario models. Based on the parameters of these models, we constructed a linear regression analysis method to evaluate whether the models in different scenarios deviated from a random distribution. Finally, we determined the possible efficacy of an antineoplastic drug in different cancer types, which was validated by the Genomics of Drug Sensitivity in Cancer (GDSC) database. Using our mining method, we tested 18 antineoplastic drugs in 16 cancer types. We found that cisplatin used in ovarian cancer was more efficacious and may benefit patients more than when used in breast cancer, which provides a new paradigm for rational knowledge-driven drug distribution patterns in clinical practice.

bioinformatics↗

bioRxiv2018

Serum glycoprotein biomarker validation for esophageal adenocarcinoma and application to Barrett’s surveillance

BACKGROUND & AIMSEsophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barretts esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker panel for BE surveillance.\n\nMETHODSSerum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and USA (1 clinic) using lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS). The area under receiver operating characteristic curve was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance.\n\nRESULTSDifferent glycoforms of complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarker candidates for EAC across both cohorts. A panel of 10 serum glycoproteins accurately discriminated BE patients not requiring intervention [BE+/-low grade dysplasia] from those requiring intervention [BE with high grade dysplasia (BE-HGD) or EAC]. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed towards EAC, levels of serum C9 glycoforms were increased with disease progression.\n\nCONCLUSIONSFurther prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted. A first-line BE surveillance blood test may be developed based on these findings.\n\nAbbreviations

biochemistry↗