Biology subjects

Yan, L.

Publications and source records attributed to Yan, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

From genomic decay to functional advantage: Trait-based evidence for long-term host residency of a next-generation coral probiotic

A key bottleneck in microbiome engineering is ensuring the long-term host association of introduced microbes. Selecting probiotic candidates based on evolutionary genomic decay signatures of emerging host dependency offers a potential solution. The Ruegeria strain B4 of the population MC10, identified by such signatures, has shown persistent colonization in corals in a companion study. Whether this persistence translates into a measurable host benefit compared to other coral-associated Ruegeria strains, and which mechanisms underlie such benefit, remained unknown. Here we directly compare the probiotic efficacy of MC10-B4 against two sympatric Ruegeria strains isolated from the same coral colony and mucus compartment, controlling for host genotype and microenvironment. MC10-B4 inoculation significantly increased heat stress tolerance in the coral model cnidarian Aiptasia (Exaiptasia diaphana strain H2), outperforming both sympatric control strains. To understand the mechanistic basis of this probiotic efficacy, we characterized the functional profile of MC10 using an integrated multi-omics approach. The genome of MC10 is enriched in genes associated with host-interaction, including siderophore-mediated iron acquisition and exopolysaccharide biosynthesis, which were phenotypically confirmed by detectable iron scavenging and enhanced biofilm formation. Following exposure to coral tissue extract, MC10-B4 underwent a coordinated motility-to-sessility proteomic reprogramming, downregulating flagellar motor components while upregulating flagellin and biofilm regulators. This response was distinct from its sympatric relatives, which instead mounted broad upregulation of nutrient acquisition systems. MC10-B4s functional profile, particularly its sensitivity to oxidative stress, contrasts with the traits typically favored in conventional probiotic screens. Our results move beyond the descriptive identification of a coral probiotic by providing initial mechanistic insight into traits associated with long-term host association and improved thermal performance. These findings validate an evolution-guided approach that prioritizes innate colonization potential over pre-defined laboratory functionalities, informing the rational design of durable probiotics.

microbiology↗

bioRxiv2025

Exercise intensity modulates the human plasma secretome and interorgan communication

Exercise is recognized as first-line therapy for many cardiometabolic diseases, including obesity, type 2 diabetes, and hypertension. Despite the abundant health-promoting effects of exercise, in-depth characterization of circulatory factors that mediate these benefits in humans remains incomplete. Moreover, how different modes and intensities of exercise uniquely regulate these processes is unclear. Here, we address these questions by conducting a multi-cohort human exercise intervention, incorporating sprint-interval exercise (SIE) and moderate-intensity exercise (MIE) to analyze intensity-dependent regulation of interorgan crosstalk. We find that exercise intensity distinctly influences the plasma proteome and metabolome in both untrained and trained participants. SIE led to immediate and robust changes to the plasma proteome, whereas MIE resulted in delayed secretory kinetics. By leveraging large, multi-organ gene and protein expression datasets, in combination with in vitro and in vivo tissue sampling, we map the differentially regulated proteins to their predicted tissue of origin and destination. We find that adipocytes are particularly sensitive to exercise intensity, undergoing broad transcriptomic remodeling following in vitro incubation with SIE as compared to MIE plasma. These findings underscore the integrated whole-body response following acute exercise and highlight exercise intensity as a key factor influencing interorgan communication.

physiology↗

bioRxiv2025

Tumors mimic the niche to inhibit neighboring stem cell differentiation

Although it is well-established that stem cells maintain tissue homeostasis while tumors disrupt it, the mechanisms by which tumors influence the development of nearby stem cells remain poorly understood. Using Drosophila ovaries as a model system, here we discovered that bam or bgcn mutant germline tumors inhibit the differentiation of neighboring wild-type germline stem cells (GSCs). Mechanistically, these tumor cells mimic the stem cell niche by secreting the BMP ligands Dpp and Gbb, but at reduced levels, resulting in moderate BMP signaling activation in adjacent GSCs. Such BMP signaling activation is sufficient to repress bam transcription, thereby blocking GSC differentiation. To our knowledge, this is the first example that tumors can functionally mimic a stem cell niche to inhibit the differentiation of neighboring wild-type stem cells. Similar regulatory paradigms may operate in mammalian tissues, including humans, during tumorigenesis.

developmental biology↗

bioRxiv2025

Structural Role of Stomatin in Organizing Functional Membrane Microdomains

Stomatin, originally discovered in red blood cells, is a member of the SPFH (Stomatin, Prohibitin, Flotillin, and HflK/C) protein family, which has long been proposed to scaffold functional membrane microdomains (FMMs) enriched in saturated lipids such as cholesterol and sphingomyelin. Stomatin has been reported to associate with a variety of proteins involved in diverse physiological processes, including ion channel regulation, membrane fusion, mechanosensory regulation and vesicle trafficking; however, the mechanisms by which it modulates these interactions remain poorly understood. Here, we determined the cryo-electron microscopy (cryo-EM) structures of stomatin, revealing its hexadecameric assemblies. The SPFH1 domains insert into the cytosolic leaflet of membranes and, together with the N-terminal hairpin, form a potential cholesterol-binding pocket. Liposome reconstitution experiments demonstrated that stomatin self-organizes into clusters, and Spectrum and Polarization Optical Tomography (SPOT) further showed that these clusters enhance membrane lipid order, supporting the proposed role of stomatin in organizing functional membrane microdomains (FMMs). Proteomic mass spectrometry analysis identified numerous stomatin-associated cargo proteins, including solute carrier (SLC) transporters, RAB GTPases, and integrins, suggesting that stomatin regulates solute transport and contributes to vesicle trafficking and cell migration. Together, these findings elucidate the structural and functional roles of stomatin and underscore its potential as a therapeutic target for modulating cancer cell migration and metastasis.

biophysics↗

bioRxiv2025

The elusive neural signature of emotion regulation capabilities: evidence from a large-scale consortium

Cognitive reappraisal is a fundamental emotion regulation strategy for mental and physical well-being, but how its neural mechanisms relate to individual differences remains poorly understood. In a consortium effort analyzing 40 fMRI datasets (N=2,175), we examined the relationship between neural activation during reappraisal tasks and three core individual difference indices of reappraisal capabilities: (1) trait questionnaires, (2) task-based affective ratings, and (3) amygdala down-regulation. Strikingly, there was no shared overlap across these three common indices. Only a very weak correlation emerged between amygdala down-regulation and task-based affective ratings. Whole-brain analyses revealed no reliable neural associations with trait questionnaires, and associations with task-based affective ratings fell outside canonical emotion regulation networks (e.g., prefrontal circuitry). Moreover, amygdala down-regulation, often interpreted as a stable individual marker, was confounded by person-specific whole-brain responses -- a limitation extending to fMRI research beyond the emotion regulation domain. These findings challenge the assumption that an individuals prefrontal activity is a valid indicator of their reappraisal capabilities and suggest that common trait, behavioral, and neural measures might capture distinct facets of emotion regulation. More broadly, our results highlight concrete methodological challenges for fMRI research on individual differences, with implications extending beyond emotion regulation to the neuroscience of personality, psychopathology, and general well-being.

neuroscience↗

bioRxiv2025

Hair Dermal papilla maintain its hair inducing characteristics via autocrine exosomal miR-23a-3p

Human dermal papilla cells (hDPCs) are specialized mesenchymal cells that regulate hair follicle development and drive the hair cycle. However, when cultured in vitro, hDPCs progressively lose their hair-inductive capacity. This decline may be closely associated with the absence of the native microenvironmental niche, which plays a critical role in maintaining hDPC identity and function in vivo. In addition to extrinsic cues, autocrine signaling within the dermal papilla itself may serve as a key mechanism for sustaining its regenerative potential. In this study, we present a novel growth model that enables real-time tracking of hDPC functional recovery, with particular attention to autocrine signaling and niche reprogramming. Our results reveal that intrinsic feedback loops are essential for maintaining hDPC function during the anagen phase. By elucidating the dynamic interplay between hDPC expansion and hair-inductive capacity, this work advances our understanding of hair follicle biology and highlights new avenues for developing regenerative therapies for hair loss.

bioengineering↗

bioRxiv2025

Acute cold exposure in humans shifts the circulating proteome to a cardioprotective and anti-aging profile

Cold exposure has been proposed to provide a constellation of salutary effects, yet its molecular correlates remain largely unknown. Brown adipose tissue (BAT) is the main site of adaptive thermogenesis, and its prevalence is linked with cardiometabolic health. Since the benefits of BAT activation and cold exposure more generally may be mediated through blood-borne factors, we conducted an extensive analysis of the circulating proteome linked with an acute cold challenge in healthy adults. Our goal was to uncover early molecular changes triggered by cooling and establish their specific relationships with the human brown adipocyte secretome as well as various phenotypic traits. Based on comprehensive inter-cohort validations, we provide the first reproducible proteomic signature of cold exposure in humans. Our data demonstrate that cooling favorably modulates circulating mediators linked with chronological aging, as well as metabolic and cardiovascular diseases, providing new potential biochemical transducers of the benefits associated with cold therapy. HighlightsO_LICooling alters the plasma proteome with striking concordance in independent human cohorts. C_LIO_LICooling represses circulating proteins linked with type 2 diabetes, hypercholesterolemia, hypertension, coronary heart disease and heart failure. C_LIO_LIThe circulating signature of cooling resembles a cardioprotective and anti-aging profile. C_LI

physiology↗

bioRxiv2025

Scutellarin inhibits ferroptosis by promoting cellular antioxidant capacity through regulating the Nrf2 signaling

Ferroptosis is a lytic form of regulated cell death that is driven by iron-dependent lipid peroxidation, and has been implicated in various diseases including acute kidney injury (AKI). Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and possesses various pharmacological activities including anti-inflammatory and antioxidative properties. Yet it is unclear whether scutellarin can inhibit ferroptosis and mitigate related diseases. In this study, we found that scutellarin was able to inhibit ferroptosis in both human HK-2 cells and mouse bone marrow-derived macrophages stimulated with RSL3 or erastin. Mitochondrial dysfunction and reactive oxygen species generation were counteracted by scutellarin treatment, suggesting involvement of its antioxidative activity. Furthermore, scutellarin increased the nuclear levels of Nrf2 and the expression of its target genes including HO-1 and GPX4. Scutellarin-mediated inhibition of ferroptosis and an increase of these proteins was abrogated by the co-treatment with brusatol, an Nrf2 inhibitor, indicating an essential role for Nrf2 in this process. In a mouse model of folic acid-induced AKI, scutellarin mitigated acute renal damage as revealed by histopathological analysis and serum blood urea nitrogen and creatinine assays. Folic acid-induced acute renal injury was associated with increased ferroptosis as revealed by elevated levels of 4-hydroxynonenal (4-HNE), a surrogate marker of ferroptosis, which were diminished by scutellarin cotreatment. Specifically, the elevated 4-HNE levels in macrophages (MAC-2 positive) and other renal cells were suppressed by scutellarin. Collectively, scutellarin can inhibit ferroptosis both in cultured cells and in a mouse model of AKI by regulating Nrf2 signaling.

pharmacology and toxicology↗

bioRxiv2025

Cryo-EM Structure of the Erlin1/2 Complex Reveals a Dynamic Scaffold for Membrane Protein Sequestration and Microdomain Assembly

The SPFH (Stomatin, Prohibitin, Flotillin, and HflK/C) family of proteins are key scaffolding components involved in the organization of functional membrane microdomains (FMMs) across various subcellular membranes, including those of the endoplasmic reticulum (ER) and mitochondria, which are characterized by a low content of saturated lipids. Among this protein family, the erlin1/2 complex is specifically located on the ER membrane. Previous studies have shown that the erlin1/2 complex plays an essential role in the ER-associated degradation (ERAD) pathway, mediating the ubiquitin-dependent degradation of various proteins such as inositol 1,4,5-trisphosphate receptors (InsP3Rs), which are important calcium ion transporters on the ER membrane. However, the molecular mechanisms underlying erlin-mediated FMMs organization and its role in ERAD remain poorly understood. In this study, we determined the single-particle cryo-electron microscopy (cryo-EM) structure of the erlin1/2 complex under different detergent conditions. Our findings reveal that the erlin1/2 complex forms a 26-mer cage-like structure, composed of alternating erlin1 and erlin2 subunits. The erlin1/2 complex defines a nanodomain on the ER membrane, which could recruit various types of proteins to both the interior and exterior membrane regions of the cage. By caging cargo proteins, the erlin1/2 complex physically secludes them from their binding partners, leading to a potential halt in their function. Moreover, individual cages can further interact with one another, facilitating the organization of FMMs of different sizes on the ER membrane. These dynamic properties may play a general and critical role in various processes occurring on the ER, including viral replication, positioning the erlin1/2 complex as a promising new target for antiviral drug development.

biophysics↗

bioRxiv2025

Single oocyte full-length isoform sequencing unveils the impact of transposable elements on RNA diversity and stability during oocyte maturation

The oocyte-specific isoforms play crucial roles in oocyte maturation, while current understanding of the oocyte transcriptome is mainly focused on gene level. Here, we utilized single cell full-length isoform sequencing based on third generation sequencing to detect entire transcripts in human and mouse oocytes. Isoform diversity during oocyte maturation was systematically profiled, including 6,736 and 4,902 putative novel human and mouse transcripts, respectively. More than half of novel isoforms were categorized as the novel-not-in-catalog (NNC) and may serve specific functions in oocytes, including novel isoforms of ARHGAP18, colocalized with microtubules and targeted knockdown disrupting oocyte maturation. Moreover, over 25% of NNC isoforms were derived from transposable elements (TEs), and their incorporation within transcripts could enhance isoform stability during oocyte maturation. Altogether, our findings represent a valuable resource showcasing the complexity and diversity of RNA isoforms in oocytes, as well as TE co-option for novel isoform generation and isoform stability enhancement.

developmental biology↗

bioRxiv2025

Uev1A counteracts oncogenic Ras stimuli in both polyploid and diploid cells

Oncogenic Ras is known to induce DNA replication stress, leading to cellular senescence or death. In contrast, we found that it can also trigger polyploid Drosophila ovarian nurse cells to die by inducing aberrant division stress. To explore intrinsic protective mechanisms against this specific form of cellular stress, here we conducted a genome-wide genetic screen and identified the E2 enzyme Uev1A as a key protector. Reducing its expression levels exacerbates the nurse cell death induced by oncogenic Ras, while overexpressing it or its human homologs, UBE2V1 and UBE2V2, mitigates this effect. Although Uev1A is primarily known for its non-proteolytic functions, our studies demonstrate that it collaborates with the E3 APC/C complex to mediate the proteasomal degradation of Cyclin A, a key cyclin that drives cell division. Furthermore, Uev1A and UBE2V1/2 also counteract oncogenic Ras-driven tumorigenesis in diploid cells, suppressing the overgrowth of germline tumors in Drosophila and human colorectal tumor xenografts in nude mice, respectively. Remarkably, elevated expression levels of UBE2V1/2 correlate with improved survival rates in human colorectal cancer patients harboring oncogenic KRAS mutations, indicating that their upregulation could represent a promising therapeutic strategy.

cell biology↗

bioRxiv2025

A reference genome assembly of the alpine forage grass Elymus nutans

Elymus nutans Griseb. (Poaceae: Triticeae, 2n=6x=42) is a dominant perennial plant species in the Qinghai-Tibetan Plateau in China, which is an important forage resource in high-altitude and cold regions and is the most popular species used for high yield artificial grassland planting because of its rich nutritional value and good palatability for herbivorous ruminant animals. In this study, using advanced sequencing technology, we generated an allohexaploid reference genome for E. nutans, representing the three sets of chromosomes (subgenomes St, Y, and H). This is the first study to our knowledge to confirm the origin of the Y subgenome, which shares a close relationship with the V subgenome. We predict that E. nutans arose via two-step hybridization and that its speciation occurred [~]3.16 MYA. The whole genome in this study will update the Triticeae family genomics information and provide theoretical basis for the evolutionary of its related speicies.

plant biology↗

bioRxiv2025

The fetal hydrops-associated single-residue mutation L322P abolishes mechanical but not chemical activation of the PIEZO1 ion channel

The mechanically activated PIEZO1 ion channel is genetically linked to numerous physiological and pathophysiological processes. For example, deleting PIEZO1 in mice leads to defective lymphatic vessel development, while nonsense mutations in humans are associated with autosomal recessive generalized lymphatic dysplasia (GLD) and non-immune hydrops fetalis. However, it remains unclear whether PIEZO1-dependent biological processes are directly mediated by its intrinsic mechanosensitivity. Here we identified a human fetal hydrops-associated single-residue mutation, L322P (corresponding to L329P in mouse PIEZO1), which completely abolishes PIEZO1s response to mechanical stimuli while maintaining normal plasma membrane expression and responsiveness to its chemical activators, Yoda1 and Jedi1. Remarkably, the mechanical response of the mutant can be restored by Yoda1. These findings demonstrate a direct link between the loss of PIEZO1s mechanosensitivity and the pathophysiological phenotype of fetal hydrops, and raise the therapeutic potential of using PIEZO1 chemical activators to restore the mechanosensitivity of PIEZO1 missense mutants that are associated with genetic diseases such as GLD and hydrops fetalis. Significance StatementGenetic deletion studies have revealed the diverse cellular, physiological, and pathophysiological roles of the mechanically activated PIEZO1 ion channel. However, whether these functions are directly mediated by its mechanosensitivity has remained experimentally unaddressed. In this study, we identified a novel fetal hydrops-associated single-residue mutation, hPIEZO1-L322P, which specifically abolishes PIEZO1s mechanical response while retaining its chemical activation. Remarkably, the mechanical response of the mutant can be fully restored by the PIEZO1 chemical activator Yoda1. These findings address the long-standing question of whether PIEZO1 relies on its mechanosensitivity to mediate in vivo functions, provide critical insights into the mechanosensing mechanism of PIEZO1, and highlight the therapeutic potential of using PIEZO1 chemical activators to rescue the loss of mechanosensitivity caused by missense mutations.

physiology↗

bioRxiv2025

Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity, learning and memory, but their evolutionary changes across species and specialized features in humans remain poorly understood. Here we performed machine learning-augmented analysis of published single-cell RNA-sequencing datasets and identified macaque imGCs with transcriptome-wide immature neuronal characteristics. Our cross-species comparisons among humans, monkeys, pigs, and mice showed few shared (such as DPYSL5), but mostly species-specific gene expression in imGCs that converged onto common biological processes regulating neuronal development. We further identified human-specific transcriptomic features of imGCs and demonstrated functional roles of human imGC-enriched expression of a family of proton-transporting vacuolar-type ATPase subtypes in development of imGCs derived from human pluripotent stem cells. Our study reveals divergent gene expression patterns but convergent biological processes in the molecular characteristics of imGCs across species, highlighting the importance of conducting independent molecular and functional analyses for adult neurogenesis in different species.

neuroscience↗

bioRxiv2025

Arabidopsis PIEZO regulates magnetic field-mediated root growth under blue light

The mechanosensitive ion channel PIEZO is known to play a role in root growth. However, whether the PIEZO gene responds to magnetic fields and the mechanisms underlying its regulation of root growth remain unclear. Here, we demonstrate that Arabidopsis PIEZO regulates root growth in response to both MF and blue light. Mutation of PIEZO led to a significantly shorter roots under MF exposure and blue light illumination. We further identified that PIEZO expression in root tips was up-regulated by a blue light-induced signal, which is transmitted from leaves to roots in the presence of a MF. PIEZO modulated calcium ion efflux and disturbed auxin transport, specifically through interactions with PIN-FORMED (PIN) 3, 6 and 7 under combined MF and blue light conditions. Notably, the blue light receptors CRYPTOCHROME 1 (CRY1) and CRY2 were essential for both MF perception and the regulation of root growth. Transcriptome analysis of the piezo-cl mutant under MF and blue light revealed that the PIEZO integrates multiple signaling pathways, including those involved in gibberellin 4 (GA4), ethylene, calcium ion-related genes, mechanosensors, and microRNAs. Specifically, miR5648-5p expression conferred MF sensitivity and provided a mechanism for the negative regulation of PIEZO under these conditions. Our findings elucidate a multifactorial mechanism by which PIEZO coordinates root growth responses to MF and blue light, integrating phytohormone signaling, mechanosensation, calcium ion dynamics, and light perception. This study highlights PIEZO as a central node in a complex network that converges diverse environmental cues to regulate root growth. One-Sentence Summary: PIEZO integrates magnetic fields and blue light signaling to regulate root growth in Arabidopsis through coordinated phytohormone, calcium, and mechanosensory pathways.

plant biology↗

bioRxiv2025

Self-iterative multiple instance learning enables the prediction of CD4+ T cell immunogenic epitopes

Accurately predicting the antigen presentation to CD4+ T cells and subsequent induction of immune response is fundamentally important for vaccine development, autoimmune disease treatments, and cancer neoepitope identification. In immunopeptidomics, single-allelic data are highly specific but limited in allele scope, while multi-allelic data contain broader coverage at the cost of weakly labeling. Existing computational approaches either overlook the massive multi-allelic data or introduce label ambiguity due to inadequate modeling strategies. Here, we introduce ImmuScope, a weakly supervised deep-learning framework integrating precise MHC-II antigen presentation, CD4+ T cell epitopes, and immunogenicity predictions. ImmuScope leverages self-iterative multiple-instance learning with positive-anchor triplet loss to explore peptide-MHC-II (pMHC-II) binding from weakly labeled multi-allelic data and single-allelic data, comprising over 600,000 ligands across 142 alleles. Moreover, ImmuScope can also interpret the MHC-II binding specificity and motif deconvolution of immunopeptidomics data. We successfully applied ImmuScope to discover melanoma neoantigens, revealing variations in pMHC-II binding and immunogenicity upon epitope mutations. We further employed ImmuScope to assess the effects of SARS-CoV-2 epitope mutations on immune escape, with its predictions aligned well with experimentally determined immune escape dynamics. Overall, ImmuScope provides a comprehensive solution for CD4+ T cell antigen recognition and immunogenicity assessment, with broad potential for advancing vaccine design and personalized immunotherapy.

bioinformatics↗

bioRxiv2025

Exosomal miR-145-5p promotes apoptosis of renal tubule epithelial cells through the JNK signalling pathway

Acute kidney injury (AKI) is the most prevalent extrapulmonary organ failure observed in patients with acute respiratory distress syndrome (ARDS). However, the underlying mechanisms leading to AKI in ARDS remain unclear. Exosomes facilitate intercellular and inter-organ communication via exosomal microRNAs (miRNAs), which potentially contribute to the crosstalk between the lung and kidney in ARDS. Therefore, the purposes of our study were to investigate the involvement of exosomal miRNAs in the development of AKI in ARDS. In current study, Sprague-Dawley rats were induced to develop ARDS via hydrochloric acid aspiration. Nanoparticle tracking analysis, Transmission electron microscopy and western blotting were conducted to analyse the exosomes. Quantitative reverse transcription-polymerase chain reaction and in situ hybridisation showed elevated expression level of miR-145-5p in the circulating exosomes and lung tissue of ARDS rats. Overexpression of miR-145-5p disrupted the proteomic profile of renal proximal tubule epithelial cells, leading to impacts on proteins associated with various biological processes, including apoptosis. We further demonstrate that miR-145-5p overexpression enhanced JNK phosphorylation by directly repressing RBM3 expression and promoted cell apoptosis. In vivo, administration of agomiR-145-5p injection via intravenous route, which subsequently induced renal tubular cell apoptosis. These findings have revealed that miR-145-5p may serve as a novel mediator for the apoptosis of renal cell in the context of ARDS.

cell biology↗

bioRxiv2024

Osthole Suppresses Prostate Cancer Progression by Modulating PRLR and the JAK2/STAT3 Signaling Axis

Prostate cancer is a common malignancy in men with limited effective treatment options, highlighting the urgent need for novel therapeutic approaches. Osthole, a natural coumarin compound with antitumor properties, has demonstrated potential in targeting various cancers. This study investigates the therapeutic effects of Osthole in prostate cancer by focusing on its ability to target the Prolactin Receptor (PRLR) and modulate the JAK2/STAT3 signaling pathway. Using a combination of network pharmacology, in vitro assays, and in vivo experiments, we first employed network pharmacology to predict Ostholes potential targets, identifying 68 targets shared with prostate cancer, including AKT1, TNF, IL6, STAT3, and CTNNB1. We then confirmed these targets and assessed the effects of Osthole on cell proliferation, migration, and apoptosis using the Cell Counting Kit-8 (CCK-8) and transwell invasion assays. To further elucidate the molecular interactions and protein expression levels, we employed molecular docking and western blot analysis. Our findings revealed that Osthole significantly inhibited prostate cancer cell proliferation and migration in a dose-dependent manner and reduced tumor volume in in vivo assays. Western blot analysis also indicated that Osthole downregulated PRLR expression and decreased the phosphorylation of JAK2 and STAT3, suggesting the inhibition of the JAK2/STAT3 pathway. These results collectively highlight the therapeutic potential of Osthole in targeting prostate cancer cells through PRLR and modulating the JAK2/STAT3 pathway, warranting further clinical exploration.

cancer biology↗