Biology subjects

yang, w.

Publications and source records attributed to yang, w..

4 recordsLinked to original sources

bioRxiv2025

hsa-miR-130b-3p Predicts Poor Prognosis Across Renal Cell Carcinoma Subtypes via CD8+T Cell Depletion: A Multi-Omics and Clinical Validation StudyImmune Evasion

Abstract BackgroundRenal cell carcinoma (RCC) is an aggressive genitourinary malignancy comprising three major subtypes: clear cell (KIRC), chromophobe (KICH), and papillary (KIRP). MicroRNAs (miRNAs) orchestrate renal cell carcinoma (RCC) progression, yet pan-subtype biomarkers remain elusive. MethodsHsa-miR-130b-3p was upregulated in all subtypes (log2FC=1.65,FDR=1.07x10- in GSE16441), correlating with poor OS (HR=1.56-2.38, p<0.05) and reduced CD8+ T cell infiltration (r=-0.32, p=0.01). Functional enrichment linked it to mTOR/HIF-1 signaling. ResultsHsa-miR-130b-3p was upregulated in all subtypes (log2FC=1.65, FDR=1.07x10- in GSE16441), correlating with poor OS (HR=1.56-2.38, p<0.05) and reduced CD8+ T cell infiltration (r=-0.32, p=0.01). Functional enrichment linked it to mTOR/HIF-1 signaling. Conclusionhsa-miR-130b-3p emerges as a simple yet powerful predictor of RCC progression and prognosis, warranting further clinical validation. As a pan-subtype biomarker (3-year AUC=0.82), hsa-miR-130b-3p may facilitate RCC immune evasion, warranting liquid biopsy validation. This study fills a gap in non-clear cell RCC (KICH/KIRP) by identifying hsa-miR-130b-3p as the first pan-subtype miRNA biomarker (3-year AUC=0.82, p<0.001), validated in 894 TCGA samples and 34 GSE16441 clinical cases. (See Figure 1 for the Graphical Abstract.) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/676345v1_fig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@18e8forg.highwire.dtl.DTLVardef@3668f5org.highwire.dtl.DTLVardef@24d6fdorg.highwire.dtl.DTLVardef@9eb696_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1C_FLOATNO Graphical Abstract C_FIG

molecular biology↗

bioRxiv2025

A polyomavirus-positive Merkel cell carcinoma mouse model supports a unified cancer origin

The Germ Cell Theory, rooted in developmental biology, has significantly advanced both the understanding and curative treatment of rare germ cell cancers (GCCs). In contrast, somatic cancer research - long dominated by the Somatic Mutation Theory - has stagnated due to fragmented, mutation-centric approaches that lack a unifying conceptual framework and have yielded only limited clinical progress. GCC research identifies non-somatic human primordial germ cells (hPGCs) as the cells of origin for GCCs. In somatic cancers, although the cancer stem cell theory is gaining acceptance, cancer stem cells are assumed to be of somatic origin, with their exact identity undefined. Accumulating experimental evidence and clinical observations challenge the traditional separation between GCCs and somatic cancers, including malignant somatic transformation (MST) - the emergence of somatic cancer phenotypes from GCCs, often without new mutations - suggesting that hPGCs may also initiate somatic cancers. However, no experimental model of MST has been established. Merkel cell polyomavirus-positive Merkel cell carcinoma (MCC), a highly aggressive somatic cancer with paradoxically stable genomes resembling those of GCCs, offers a unique model to test germ cell theory-based somatic oncogenesis. Here we present an MST mouse model linking hPGC origin to somatic cancer by inducing virus-positive MCC-like tumors in vivo from virus-transfected hPGC-like cells or human iPSCs competent for hPGC specification with an obligatory late-hPGC state preceding MST. This genetically simple, molecularly tractable model provides a novel platform to dissect VP-MCC pathogenesis and broadly advocates a developmental biology framework for somatic cancer research beyond mutation-centric and soma-centric paradigms.

cancer biology↗

bioRxiv2023

Force sensation by a Gs-coupled adhesion GPCR mediates equilibrioception by increasing vestibular hair cell membrane excitability and CNGA3 coupling

AbstractEquilibrioception is essential for the perception and navigation of mammals in the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells plays a critical role in positional and motional perception. Here, we identified that the G protein-coupled receptor LPHN2/ADGRL2, which is expressed in the apical membrane of utricular hair cells, is required for maintenance of normal balance. Hair cell-specific Lphn2 deficiency in mice impaired both balance behaviors and MET responses. Functional analyses using Pou4f3-CreER+/-; Lphn2fl/fl mice and LPHN2-specific inhibitors revealed that LPHN2 regulated the tip link-independent MET current at the apical surface of the utricular hair cell by converting force stimuli into transmembrane channel-like protein 1 (TMC1) activity. Force sensation by LPHN2 also induced glutamate release and calcium signaling in utricular hair cells. Reintroduction of LPHN2 into the hair cells of Lphn2-deficient mice restored the vestibular functions and MET responses. Our data suggest an indispensable role for a mechanosensitive GPCR in equilibrioception.

physiology↗

bioRxiv2019

Changes in the expression of interleukin-10 in myocardial infarction and its relationship with macrophage activation and cell apoptosis

Currently, the role of IL-10 as an anti-inflammatory factor in the occurrence and development of heart disease is still unclear. This study aimed to observe the dynamic changes in the expression of IL-10 in serum and myocardial tissues, as well as to investigate the relationship of IL-10 expression with macrophage activation and cardiomyocyte apoptosis during the occurrence of myocardial infarction. Mice models with myocardial infarction were prepared by ligating anterior descending branch of the coronary artery. The animals were classified into sham operation group (the control group), as well as groups of myocardial infarction based on days 1, 7, 14 and 28. On days 7 and 14, the cells with positive IL-10 expression were largely distributed in the infarct areas, while cells with positive IL-10 expression were decreased on day 28. Serum IL-10 was significantly positively correlated with IL-10 protein expression in myocardial tissues. Moreover, Bcl-2 and Bax protein expression in myocardial tissues, as well as the ratio of Bcl-2/Bax proteins were gradually elevated with prolonged time of infarction. There were positive correlations between IL-10 and Arginase expressions, and between the expressions of Bcl-2 and Bax proteins. After the occurrence of myocardial infarction, the expression of IL-10 was firstly increased and then decreased in serum and myocardial tissues, and this might affect macrophage activation, phenotypic transformation and the occurrence of cardiomyocyte apoptosis.

cell biology↗