Biological Procedures Online最新文献

{"title":"Single-Cell RNA Sequencing Identifies a Distinct Epithelial Subpopulation Driving Resistance to Neoadjuvant Chemoimmunotherapy in Esophageal Squamous Cell Carcinoma.","authors":"Zuoyu Chen, Xin Yu, Kaili Liu, Yiping Zou, Xue Ding, Xiaolong Zhang, Liangliang Wu, Qiang Song, Hailong Wang","doi":"10.1186/s12575-026-00337-1","DOIUrl":"10.1186/s12575-026-00337-1","url":null,"abstract":"<p><p>BACKGROUND: To investigate the role and mechanism of the transcription factor ETS2 in mediating resistance to neoadjuvant immunotherapy combined with chemotherapy in esophageal squamous cell carcinoma (ESCC). METHODS: Single-cell RNA sequencing (scRNA-seq) was performed on tumor tissues from ESCC patients who received neoadjuvant therapy. Integrated analyses were conducted using clinical information, genomic and transcriptomic data from public databases (TCGA) and a single-center patient cohort. Weighted gene co-expression network analysis (WGCNA) was employed to identify senescence-associated gene modules. The association between ETS2 expression and cellular senescence or signaling pathway activity was evaluated using gene set enrichment analysis (GSEA) and computational scoring of senescence-related gene sets. RESULTS: ETS2-high epithelial cells were localized at the terminal end of the differentiation trajectory inferred by pseudotime analysis and were enriched in tumors with poor treatment response. ETS2 was highly expressed in ESCC tumor tissues and significantly associated with adverse patient outcomes. Transcriptomic analysis (TCGA) demonstrated significant enrichment of TGF-β in the ETS2-high group. WGCNA identified a senescence-associated “coral” gene module, whose expression was significantly correlated with patient age and induced senescence gene set scores, and exhibited the strongest association with senescence among all modules. CONCLUSION: High expression of ETS2 in ESCC predicts poor prognosis and resistance to neoadjuvant therapy. Its mechanism may involve inducing a senescent state in tumor cells and promoting aggressive tumor behavior through activation of key signaling pathways such as TGF-β. The “coral” module identified by WGCNA represents a critical senescence-related gene signature in ESCC. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13220492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Role of Oxidative Stress-Associated Genes FKBP Prolyl Isomerase 5 in Osteoarthritis Development and Immunological Milieu.","authors":"Liangkun Huang, Zhongyu Peng, Ya Wen, Ze Zhang, Zijie Pei, Hanzhe Xu, Liangyuan Wen","doi":"10.1186/s12575-026-00336-2","DOIUrl":"10.1186/s12575-026-00336-2","url":null,"abstract":"<p><p>BACKGROUND: Oxidative stress arises from disrupted equilibrium between reactive oxygen species generation and cellular antioxidant capacity, serving as a pivotal mechanism in inflammatory pathology, particularly osteoarthritis development. The progression of osteoarthritis-related pain may additionally involve oxidative stress through its activation of nociceptive signaling pathways, but the mechanism of its influence on the progression of osteoarthritis is not yet unanimous. METHODS: The study utilized publicly available sequencing data, which included specimens from patients with osteoarthritis and matched healthy controls, retrieved from GEO database, and combined them after removing batch effects. A multi-step analytical approach was employed to identify pivotal diagnostic biomarkers for osteoarthritis. This strategy encompassed examining differential gene expression, constructing protein-protein interaction networks, applying machine learning algorithms, and assessing co-expression patterns. Subsequently, a diagnostic framework incorporating a nomogram was developed based on these candidate genes. To discern distinct patient subgroups, cluster analysis was conducted. Further investigations into the underlying biology revealed divergent functional pathways and immune cell infiltration landscapes across the identified subtypes, highlighting the putative roles of the key biomarkers. We investigated the effects of FKBP5 on osteoarthritis through both in vivo and in vitro experiments, examining chondrocyte proliferation capacity, apoptosis, cellular senescence, mitochondrial function, and cartilage degeneration. RESULT: We successfully screened the key genes PPARGC1A, FKBP5, and MMP13 for the diagnosis of osteoarthritis, constructed a diagnostic model and a nomogram of osteoarthritis, and verified their excellent diagnostic ability. Based on these core genes we classified osteoarthritis into two subtypes. Enrichment analysis and immune infiltration analysis confirmed that FKBP5 regulates the immune microenvironment in osteoarthritis and influences the progression of osteoarthritis. Both in vivo and in vitro experiments confirmed that FKBP5 overexpression enhances chondrocyte viability, proliferative capacity, and mitochondrial function under inflammatory conditions, while reducing cellular senescence, apoptosis, and cartilage degeneration. FKBP5 may serve as a potential therapeutic target for osteoarthritis intervention. CONCLUSION: Our study identified distinct molecular subtypes of osteoarthritis by analyzing genes associated with oxidative stress. Furthermore, we found that FKBP5 exerts a positive regulatory effect on chondrocyte function and mitigates cartilage degeneration in the osteoarthritis environment. This provides new insights for personalized treatment of osteoarthritis. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of RBM15 in the Immune Escape of Non-small Cell Lung Cancer Cells Via the LncRNA EGFR-AS1/USP3/PD-L1 Axis.","authors":"Fang Li, Zhao Zhang, Shuai Liu, Yang Wang, Xiang Deng, Jiasheng Wang","doi":"10.1186/s12575-026-00329-1","DOIUrl":"10.1186/s12575-026-00329-1","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is the most prevalent subtype of lung cancer, with persistently low overall cure and survival rates, largely attributed to tumor immune escape. This study aims to explore the role of RBM15 in the immune escape of NSCLC and provide a potential therapeutic target. Firstly, RBM15, LncRNA EGFR-AS1, PCBP2, USP3, and PD-L1 were detected in NSCLC cells. Peripheral blood mononuclear cells (PBMCs) were co-cultured with NSCLC cells to assess PBMC cytotoxicity, CD8⁺T and CD107a+CD8+T cell proportion, and levels of IFN-γ, IL-10, and IL-2. To verify the mechanism, m6A enrichment on EGFR-AS1 was analyzed. The m6A modification sites on EGFR-AS1 were assayed. The interactions among EGFR-AS1-PCBP2, PCBP2-USP3, and USP3-PD-L1 were detected. We found that RBM15, EGFR-AS1 and PCBP2 were upregulated in NSCLC cells. Mechanistically, RBM15 stabilized EGFR-AS1 through m6A modification, increased the binding of EGFR-AS1 to PCBP2, and promoted USP3 expression. USP3 bound to PD-L1 and inhibited PD-L1 ubiquitination and degradation. In PBMC-NSCLC co-cultures, RBM15 downregulation increased PBMC cytotoxicity, CD8⁺T cell proportion, IFN-γ/IL-2 levels, and decreased IL-10 levels—effects partially reversed by EGFR-AS1 or USP3 overexpression. In conclusion, RBM15 enhances the immune escape of NSCLC through the EGFR-AS1/USP3/PD-L1 axis via m6A modification.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA hsa_circ_0003472 Promotes Pancreatic Ductal Adenocarcinoma Progression and Gemcitabine Resistance Via the mir-1253/ERCC1 Axis.","authors":"Cunbing Xia, Yang Chen, Xindong Yin, Yongkang Zhu, Gaoyuan Wang, Dexuan Chen, Tong Shen, Xiaojun Yang, Haijian Sun, Hong Zhu","doi":"10.1186/s12575-026-00335-3","DOIUrl":"10.1186/s12575-026-00335-3","url":null,"abstract":"<p><p>BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies with limited therapeutic options. Circular RNAs (circRNAs) have emerged as critical regulators of cancer progression; however, the functional role of hsa_circ_0003472 in PDAC remains unexplored. METHODS: Expression of hsa_circ_0003472 was assessed in 30 paired PDAC and adjacent normal tissues and pancreatic cancer cell lines using quantitative RT-PCR. Loss-of-function experiments were performed to evaluate effects on proliferation (CCK-8, EdU), apoptosis (TUNEL, Western blot), migration, and invasion (Transwell assays). Gemcitabine sensitivity was determined by IC50 analysis. Bioinformatic prediction and dual-luciferase reporter assays identified the downstream regulatory axis. Xenograft mouse models validated findings in vivo. RESULTS: hsa_circ_0003472 was significantly upregulated in PDAC tissues and cell lines. Silencing hsa_circ_0003472 inhibited proliferation, migration, and invasion while promoting apoptosis and enhancing gemcitabine sensitivity. Mechanistically, hsa_circ_0003472 functioned as a competing endogenous RNA by sponging miR-1253, thereby relieving suppression of excision repair cross-complementing group 1 (ERCC1). Rescue experiments confirmed that the oncogenic effects of hsa_circ_0003472 were mediated through the miR-1253/ERCC1 axis. In vivo, hsa_circ_0003472 knockdown significantly reduced tumor growth and recapitulated molecular changes observed in vitro. CONCLUSION: hsa_circ_0003472 promotes PDAC progression and chemoresistance through the miR-1253/ERCC1 regulatory axis, representing a potential therapeutic target for this devastating malignancy. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP7 Drives Atherosclerosis by Promoting Ferroptosis in Vascular Endothelial Cells via the KIAA1429/NEAT1/CTCF Axis.","authors":"Bo Dong, Lu Kou, Jing-Yu Yang, Yang Li, Ning Yang","doi":"10.1186/s12575-026-00331-7","DOIUrl":"10.1186/s12575-026-00331-7","url":null,"abstract":"<p><p>BACKGROUND: Ferroptosis is an iron-dependent form of necrosis that promotes AS by accelerating endothelial dysfunction in lipid peroxidation. This study aims to investigate the role of deubiquitinase USP7 in ferroptosis of VECs during AS. METHODS: AS models were established using HFD-fed ApoE−/− mice in vivo and ox-LDL-treated HUVECs in vitro. After USP7 inhibition, plaque area and necrotic core in aortas were assessed by Oil-red O and H&E staining. TC, TG, HDL-C, and LDL-C were measured, and iron content, ROS, MDA, and GSH levels in tissues and cells were quantified. USP7, KIAA1429, lncRNA NEAT1, GPX4 and SLC7A11 expression were analyzed by qRT-PCR or Western blot. Cell viability was assessed by CCK-8 assay. Protein interactions between USP7 and KIAA1429 and ubiquitination level of KIAA1429 were detected via Co-IP. Total m6A levels were quantified. M6A enrichment on NEAT1 was measured by MeRIP. Binding between KIAA1429 and NEAT1 was detected. Bindings between YTHDF1 and NEAT1, and between NEAT1 and CTCF were detected by RIP. CTCF binding and H3K27me3 enrichment at the SLC7A11 promoter were analyzed by ChIP. RESULTS: USP7, KIAA1429, and NEAT1 were upregulated in mouse AS models and ox-LDL-treated HUVECs. USP7 inhibition attenuated AS pathology and VECs ferroptosis. USP7 deubiquitinated and stabilized KIAA1429, which facilitated YTHDF1-mediated m6A modification to stabilize NEAT1. NEAT1 recruited CTCF to maintain H3K27me3 modification at the SLC7A11 promoter, repressing SLC7A11 transcription and triggering HUVECs ferroptosis. Overexpression of KIAA1429 or NEAT1 reversed protective effects of USP7 inhibition on ferroptosis. CONCLUSION: USP7 promotes VECs ferroptosis in AS via the KIAA1429/NEAT1/CTCF axis. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragaloside IV Suppresses Gastric Cancer by m6A-dependent FSP1 Modulation and Ferroptosis Induction.","authors":"Wei Yin, Xi Chen, Bi Chen, Xiaodi Xu, Wenxian Guan, Haixiao Wang, Yang Su","doi":"10.1186/s12575-026-00327-3","DOIUrl":"10.1186/s12575-026-00327-3","url":null,"abstract":"<p><p>BACKGROUND: Astragaloside IV (AS-IV), a key active component derived from the traditional Chinese medicinal plant Astragali, has been reported to exhibit various biological activities, including antioxidative, anti-inflammatory, immunoregulatory, and antineoplastic properties. This study aimed to elucidate the role of AS-IV in inhibiting gastric cancer (GC) growth, focusing on its impact on cell ferroptosis and the underlying molecular mechanisms. METHODS: Proliferation and migration of GC cells upon AS-IV treatment were examined using CCK-8, colony formation, and Transwell assays. Ferroptosis induction was analyzed via ELISA, flow cytometry, and transmission electron microscopy. Ferroptosis suppressor protein 1 (FSP1) mRNA stability was assessed by the ActD assay, while RNA immunoprecipitation (RIP) was employed to confirm the interaction between FSP1 mRNA, Fat mass and obesity-associated protein (FTO) demethylase, and YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2). The dual-luciferase reporter assay was used to explore FTO binding to N6-methyladenosine (m6A)-modified sites on FSP1 mRNA. Furthermore, AS-IV’s anti-tumor effects (20 mg/kg) were validated in vivo using gastric cancer xenograft and lung metastasis mouse models. RESULTS: AS-IV significantly suppressed the proliferation and migration of GC cells by inducing ferroptosis. Mechanistically, AS-IV down-regulated FTO, thus impairing its interaction with FSP1 mRNA and leading to increased m6A modification on FSP1 mRNA. This modification facilitated m6A recognition protein YTHDF2-mediated recognition and subsequent degradation of FSP1 mRNA. The reduction of FSP1 triggered ferroptosis, while the overexpression of FSP1 or inhibition of ferroptosis by ferrostatin-1 partially reversed AS-IV’s effects on cell viability and migration. In vivo, AS-IV effectively inhibited tumor growth and metastasis. CONCLUSIONS: This study highlights potent anti-GC effects of AS-IV, mediated by the suppression of FSP1 via the FTO/YTHDF2/m6A axis. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conventional and Novel Approaches to Establishing Mouse Models of Gastric Cancer in the Past, Present, and Potential Post-H. Pylori Infection Era.","authors":"Hui Liu, Yunxiao Ge, Kangdong Liu, Zigang Dong","doi":"10.1186/s12575-026-00333-5","DOIUrl":"10.1186/s12575-026-00333-5","url":null,"abstract":"<p><p>Gastric cancer remains a major cause of global cancer-related morbidity and mortality. Mouse models are indispensable tools for preclinical research into its mechanisms and therapies. Although Helicobacter pylori (H. pylori) infection is the primary risk factor for gastric cancer, developing mouse models based on this pathogen faces significant challenges. These include low bacterial colonization and survival rates, unpredictable and protracted tumorigenesis timelines, restrictions of host genetic backgrounds, the complexity of inflammatory and immune microenvironments, difficulties in standardized pathological assessment, and poor model reproducibility. In light of these limitations, research efforts have diversified into four principal categories of modeling approaches: chemical carcinogen-induced models, microbe-infected models (particularly those involving H. pylori), xenograft models, and genetically engineered mouse models. Each strategy offers distinct advantages and constraints, necessitating careful selection based on specific research objectives. This review comprehensively examines both conventional and emerging methods for establishing gastric cancer mouse models, situating them within a historical and evolving research landscape from past reliance on H. pylori to present and future approaches in the potential post-H. pylori infection era. We emphasize the applicability and compatibility of each modeling system with particular research goals, providing critical insights for selecting optimal in vivo platforms to advance the study of gastric carcinogenesis.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Diagnosis between Sintilimab-related Autoimmune Myocarditis and Acute Myocardial Infarction.","authors":"Yihe Wu, Jiayun Nian, Hongxu Liu, Xiaolei Lai, Zihao Liu, Tengfei Li, Shenglei Qiu","doi":"10.1186/s12575-025-00267-4","DOIUrl":"10.1186/s12575-025-00267-4","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the regularities and clinical features of sintilimab-related autoimmune myocarditis, and to summarize the differential diagnosis key points between sintilimab-related autoimmune myocarditis and acute myocardial infarction.</p><p><strong>Methods: </strong>The case reports about sintilimab-related autoimmune myocarditis were searched on databases from the establishment of the database to April 1st 2024. The relevant medical records were searched on the hospital information system of Beijing Hospital of Traditional Chinese Medicine in the past 3 years. The case reports and medical records were collected for statistical analysis.</p><p><strong>Result: </strong>Twenty three cases were collected including 22 case reports and 1 case record. Most of the sintilimab-related autoimmune myocarditis were in elderly men aged 60-75 years old and occurred between the end of the first dose of treatment to the beginning of the second dose. The symptom was nonspecific such as chest tightness and palpitation, sometimes with symptom of myasthenia as muscle weakness or myositisand as muscle soreness. Elevated cardiac biomarkers and changes in electrocardiogram were common, and decreased left ventricular ejection fraction was rarely seen in echocardiography. 9 cases underwent coronary angiography or computed coronary tomography angiography, and 3 cases underwent cardiovascular magnetic resonance.</p><p><strong>Conclusion: </strong>The manifestations of sintilimab-related autoimmune myocarditis are not specific. The medication history and concomitant symptoms are of warning value. Coronary angiography or coronary computed coronary tomography angiography can be helpful when ruling out acute myocardial infarction. Cardiovascular magnetic resonance and myocardial biopsy can confirm the diagnosis. Cardiac biomarkers and the electrocardiogram can assist in diagnosis and prognosis assessment.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH5 promotes ovarian cancer progression by activating Notch2 signaling.","authors":"Yanying Liu, Huafeng Luo, Luhong Li, Ziao Gao, Qian Wang, Hao Liu, Ruiyun Wu, Cong Peng","doi":"10.1186/s12575-026-00330-8","DOIUrl":"10.1186/s12575-026-00330-8","url":null,"abstract":"<p><strong>Background: </strong>ALKBH5, one of the RNA N6-methyladenosine (m6A) demethyltransferases, has been suggested to be involved in the progression of several cancers. The aim of this study was to investigate clinical significance and biological functions of ALKBH5 in promoting ovarian cancer progression.</p><p><strong>Results: </strong>We found a significant upregulation of ALKBH5 expression in ovarian cancer tissues compared with normal tissues. Correlation analyses indicated an association between heightened ALKBH5 expression and FIGO stage, as well as lymph node metastasis. Importantly, increased ALKBH5 expression indicated shorter progression-free survival and overall survival. Moreover, we found that hypoxia induced an increase in ALKBH5 expression in ovarian cancer via an HIF-1α-dependent mechanism. Loss-of-function assays demonstrated that ALKBH5 knockdown inhibited ovarian cancer cell progression both in vitro and in vivo. Furthermore, we found that knockdown of ALKBH5-meidated m6A demethylation decreased Notch2 mRNA stability and expression, resulting in the inhibition of cell proliferation, invasion and metastasis in OC cells.</p><p><strong>Conclusion: </strong>In summary, our findings demonstrated that ALKBH5 promotes the progression of ovarian cancer by activating Notch2 signaling, and suggested that ALKBH5 functions as an oncogene and may serve as a prognostic biomarker and therapeutic target in ovarian cancer.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key molecular mechanisms and regulatory networks in colorectal cancer liver metastasis.","authors":"Zhipeng Zhang, Yuchun Ni, Jie Wang, Jianhui Tian, Likun Liu, Shulan Hao","doi":"10.1186/s12575-026-00332-6","DOIUrl":"10.1186/s12575-026-00332-6","url":null,"abstract":"<p><p>Colorectal cancer (CRC) continues to show rising incidence and mortality worldwide, with liver metastasis representing the leading cause of death among affected patients. Epidemiological data indicate that approximately 49% of CRC-related deaths are associated with hepatic metastases, and about 25% of patients still develop liver metastasis even after undergoing curative resection. The interplay of various cytokines and immune cells within the tumor microenvironment (TME), along with tumor metabolic reprogramming and gut microbiota, collectively underpins the process of colorectal cancer liver metastasis (CRLM). To date, multiple genes, signaling pathways, and cellular components have been identified as key contributors to the development of CRLM. Although the precise mechanisms driving CRLM remain incompletely understood, emerging evidence suggests that liver metastasis is not restricted to advanced CRC stages and may already be present in a subset of early-stage patients. Based on current evidence, this review proposes that effective anti-metastatic strategies should shift from single-pathway targeting toward integrated interventions that simultaneously regulate the following three dimensions: circulating tumor cells (and their EMT process) as the ‘seeds’, the tumor microenvironment as the ‘soil’, and the gut microbiota and metabolic reprogramming as the ‘environmental modifiers’. This article systematically summarizes the mechanisms and recent advances in the molecular regulatory networks underlying colorectal cancer liver metastasis, with a particular focus on the roles of immune cells and related cytokines in the tumor microenvironment. It aims to provide new insights and potential therapeutic targets for the comprehensive management of this disease and highlights the need to further investigate interactions among these mechanisms, accelerate the development of translational biomarkers, and thereby drive key breakthroughs in the field.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13059156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}