Gene最新文献

{"title":"Nonylphenol-responsive MIR200CHG modulates colorectal cancer cell proliferation, migration, and invasion through EPS8L1.","authors":"Lin Dai, Lei Wan, Nianjie Zhang, Biao Wang, Yuchang Zhong, Xuefeng Yang","doi":"10.1016/j.gene.2026.150488","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150488","url":null,"abstract":"<p><strong>Background: </strong>Nonylphenol (NP), an environmental endocrine disruptor, has been associated with changes in colorectal cancer (CRC) cell proliferation and motility. The contribution of NP-responsive long non-coding RNAs (lncRNAs) to these effects remains unclear.</p><p><strong>Objective: </strong>To investigate the role of MIR200CHG in NP-associated CRC cell proliferation, migration, and invasion and examine its relationship with EPS8L1 expression and ERK1/2 phosphorylation.</p><p><strong>Methods: </strong>MIR200CHG and EPS8L1 expression was examined in public CRC datasets and six paired CRC and adjacent noncancerous tissue specimens. After assessing MIR200CHG responses to NP at 10^-7, 10^-6, and 10^-5 M for 24 h, 10^-6 M was selected for subsequent cell experiments. MIR200CHG gain- and loss-of-function experiments were used to examine CRC cell proliferation, migration, and invasion; E-cadherin, N-cadherin, and vimentin protein expression was assessed by western blotting. Candidate MIR200CHG-associated genes were screened using ENCORI. Dual-luciferase reporter assays and actinomycin D mRNA-stability assays were performed to evaluate the post-transcriptional regulatory relationship between MIR200CHG and EPS8L1. Reciprocal rescue experiments were used to assess the functional contribution of EPS8L1, and ERK1/2 phosphorylation was examined by western blotting. In vivo, subcutaneous HCT116 xenografts were used to evaluate tumor growth under MIR200CHG knockdown with or without NP treatment.</p><p><strong>Results: </strong>MIR200CHG and EPS8L1 expression was higher in the CRC tumor tissues, consistent with the expression patterns observed in public CRC datasets. NP increased MIR200CHG expression in CRC cells. In cultured CRC cells, MIR200CHG overexpression enhanced proliferation, migration, and invasion, whereas knockdown reduced these phenotypes. These changes were accompanied by decreased E-cadherin and increased N-cadherin and vimentin after overexpression, with the opposite pattern after knockdown. Dual-luciferase reporter assays supported site-dependent regulation of EPS8L1, while actinomycin D assays indicated that MIR200CHG enhances EPS8L1 mRNA stability. EPS8L1 knockdown attenuated, whereas EPS8L1 overexpression restored, the MIR200CHG-associated phenotypes. MIR200CHG knockdown reduced subcutaneous xenograft growth, while NP treatment increased growth within the knockdown setting. Changes in ERK1/2 phosphorylation accompanied MIR200CHG and EPS8L1 manipulation.</p><p><strong>Conclusion: </strong>NP-responsive MIR200CHG contributes to CRC cell proliferation, migration, and invasion. Reporter, mRNA-stability, and rescue experiments support EPS8L1 as a downstream regulator of these cellular responses. ERK1/2 phosphorylation changes were associated with MIR200CHG and EPS8L1 manipulation, while the xenograft findings support a role for MIR200CHG in primary tumor growth.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150488"},"PeriodicalIF":2.7,"publicationDate":"2026-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149378376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative network toxicology and clinical validation identify CD4, PTGS2, and KDR as candidate targets of nicotine in infantile hemangioma.","authors":"Shulin Luo, Ziliang Chen, Dequan Liu, Mingde Liao, Jinglu Hu, Feiyi Du, Chong Liu, Bojie Lin","doi":"10.1016/j.gene.2026.150485","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150485","url":null,"abstract":"<p><p>Infantile hemangioma (IH) is the most common benign vascular tumor of infancy. Perinatal tobacco smoke exposure has been associated with pediatric benign tumors, but a specific molecular link between nicotine and IH has not been established. We aimed to identify and validate candidate targets of nicotine in IH. Age-stratified differentially expressed genes (6, 12, and 24 months) from GSE127487 were intersected with IH- and nicotine-related targets and prioritized by network analysis, followed by enrichment analysis, immune deconvolution, and molecular docking, with tissue validation and machine-learning screening of a clinical cohort (77 patients, 50 controls). CD4, PTGS2, and KDR were core targets shared across age groups, whereas EGFR, PPARG, TLR4, and ACE were stage-restricted; enrichment converged on PI3K-Akt, MAPK, HIF-1, and VEGF signaling. Nicotine showed computationally plausible docking to KDR (-6.91 kcal/mol) and PTGS2 (-6.39 kcal/mol). CD4 and PTGS2 proteins were markedly upregulated in IH lesions, with KDR showing a concordant upward trend (paired t-test: P < 0.001, P < 0.001, and P = 0.062, respectively). Single-cell re-analysis placed KDR in GLUT1-positive lesional endothelium and CD4 transcripts mainly in myeloid and mural cells. A four-indicator blood signature (globulin, mean platelet volume, platelet distribution width, and total protein; AUC 0.942, 95 % CI 0.859-1.000) reflected the associated immune-inflammation state. These hypothesis-generating results nominate a CD4-, PTGS2-, and KDR-centered network converging on angiogenic and inflammatory signaling as a candidate route through which nicotine may act in IH. These candidate targets and the blood signature require external-cohort and mechanistic validation.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150485"},"PeriodicalIF":2.7,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149370371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MESP1 is transcriptionally activated by TFAP2A to promote malignant phenotypes and glycolysis in non-small cell lung cancer cells.","authors":"Zhiping Lv, Yang Liu, Rui Qiu, Sheng Zhang, Wei He","doi":"10.1016/j.gene.2026.150477","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150477","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is a highly prevalent malignant tumor worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases and carrying a poor prognosis for patients. Mesoderm posterior basic helix-loop-helix (bHLH) transcription factor 1 (MESP1) encodes a bHLH transcription factor, and its mechanism in NSCLC remains incompletely understood.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were identified through an integrated analysis of gene expression omnibus (GEO) datasets. Core genes were selected using least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) machine learning algorithms, and their association with lung cancer risk was evaluated through logistic regression analyses. Western blot was used to detect protein expression. Cellular functions were assessed via colony formation, sphere formation, Transwell migration and invasion, extracellular acidification rate (ECAR), and lactate production assays. Upstream transcriptional regulatory mechanisms were validated using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays.</p><p><strong>Results: </strong>A total of 106 common DEGs were identified, with SERTM1, PYCR1, and MESP1 selected through machine learning. Logistic regression confirmed MESP1 as an independent risk factor for lung cancer, exhibiting significantly elevated expression across multiple datasets. In vitro experiments demonstrated that MESP1 knockdown markedly suppressed colony formation, stemness, migration, invasion, ECAR, and lactate production, as well as glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2) protein expression in NSCLC cells. Mechanistic studies revealed that transcription factor AP-2α (TFAP2A) directly bound to the MESP1 promoter to activate its transcription, and MESP1 mediated the promotion effects of TFAP2A in vitro.</p><p><strong>Conclusion: </strong>MESP1 is highly expressed in NSCLC and transcriptionally regulated by TFAP2A. These findings unveil a novel TFAP2A/MESP1 regulatory axis in NSCLC that promotes malignant phenotypes and glycolysis. This axis may provide a potential molecular basis for the development of targeted strategies, although further in vivo validation is warranted.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150477"},"PeriodicalIF":2.7,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149320032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZC3H13 promotes cervical cancer cell proliferation and stemness and reduces cisplatin sensitivity and apoptosis by stabilizing CTHRC1 mRNA in an m⁶A-Dependent manner.","authors":"Fanerke Aihemaitijiang, Xinyuan Meng, Ayizhadan Yumai, Yalikun Muhanmude","doi":"10.1016/j.gene.2026.150474","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150474","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) remains a global health burden. N⁶-methyladenosine (m⁶A) modification regulated by ZC3H13 is critical in carcinogenesis. Collagen triple helix repeat containing 1 (CTHRC1) is dysregulated in multiple malignancies, but the role of the ZC3H13/CTHRC1 axis in the malignant progression of CC stemness and cisplatin sensitivity remains unclear.</p><p><strong>Methods: </strong>Bioinformatic analyses, including differential gene screening, weighted gene co-expression network analysis, random forest, least absolute shrinkage and selection operator, and support vector machine recursive feature elimination, were performed on the GSE63514 dataset to identify core genes. SRAMP was used to predict m⁶A sites on CTHRC1 mRNA. Gene expression was detected by quantitative real-time PCR and western blot. Cell proliferation, stemness, apoptosis, and cisplatin sensitivity were assessed by EdU, tumorsphere formation, CD44 flow cytometry, Annexin V-PI staining, and CCK-8 assay, respectively. Regulatory mechanisms were explored by RNA immunoprecipitation (RIP), methylated RIP, and mRNA stability assays, and verified by rescue experiments.</p><p><strong>Results: </strong>Bioinformatic analysis identified CTHRC1 as a core upregulated gene in CC (P = 8.4e-10). CTHRC1 depletion inhibited proliferation, stemness, and promoted cisplatin sensitivity and apoptosis. ZC3H13 was overexpressed in CC (P < 0.001) and positively correlated with CTHRC1 (r = 0.578, P < 0.001). ZC3H13 knockdown decreased CTHRC1 expression and m⁶A enrichment on CTHRC1 mRNA, accompanied by reduced mRNA stability. CTHRC1 overexpression rescued the phenotypes induced by ZC3H13 knockdown.</p><p><strong>Conclusion: </strong>The ZC3H13/CTHRC1 axis modulates CC stemness and cisplatin sensitivity through an m⁶A-dependent mRNA stabilization mechanism, laying a solid molecular foundation for developing novel anti-cervical cancer strategies.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150474"},"PeriodicalIF":2.7,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149320049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced epigenetic reprogramming of cancer stem cells: Linking stemness, metastasis, and therapy resistance.","authors":"Mutaz Jamal Al-Khreisat, Rustam Narzikulov, Omer Qutaiba B Allela, Asyl Fatk Tmkyn, Priya Priyadarshini Nayak, Abdusamat Rasulov, Shamuratova Gulnora Baxtiyorovna, Neeraj Bainsal","doi":"10.1016/j.gene.2026.150463","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150463","url":null,"abstract":"<p><p>Hypoxia is a defining feature of the solid tumor microenvironment and a central driver of cancer-stem-cell (CSC) biology, yet the epigenetic mechanisms linking oxygen deprivation to stemness, metastasis, and therapy resistance remain fragmented across the literature. This review synthesizes that evidence into a unified mechanistic framework. Beyond the canonical hypoxia-inducible factor (HIF)-1α/HIF-2α switch, hypoxia directly reprograms the epigenome through oxygen-dependent histone demethylases and DNA dioxygenases (TET, JmjC-domain enzymes), establishing chromatin as a parallel, HIF-adjacent oxygen sensor. This crosstalk spans DNA methylation dynamics that gate HIF binding while HIF reciprocally reshapes DNMT/TET expression; histone modifications that redistribute genome-wide and are selectively co-opted at pluripotency loci; and histone lactylation, a metabolically-derived mark we position as an emerging fourth epigenetic pillar - though, as detailed below, its mechanistic demonstration within defined CSC populations remains more preliminary than for the other three layers. We trace how these layers converge on the core pluripotency circuitry (OCT4, SOX2, NANOG, KLF4, MYC), critically examine the limited evidence for a \"hypoxic memory\" outlasting reoxygenation - currently demonstrated only in bulk tumor and circulating-tumor-cell populations, not defined CSCs - and connect these mechanisms to EMT, circulating-tumor-cell survival, and multi-modal therapy resistance. We distinguish mechanisms demonstrated directly in CSCs from those inferred from general cancer contexts, identifying histone lactylation in CSCs and true post-reoxygenation memory as areas needing further investigation.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150463"},"PeriodicalIF":2.7,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis of patients with loss-of-function POGZ variants in four unrelated Chinese families","authors":"Yong Wu ,&nbsp;Na Liang ,&nbsp;Fengyuan He ,&nbsp;Bo Tan","doi":"10.1016/j.gene.2026.150070","DOIUrl":"10.1016/j.gene.2026.150070","url":null,"abstract":"<div><div>Intellectual disability (ID) and autism spectrum disorders (ASD) are complex neurodevelopmental disorders (NDDs) with a strong genetic component, and recent studies have highlighted the <em>POGZ</em> gene on chromosome 1q21.3 as a significant contributor, particularly linked to White-Sutton syndrome (WHSUS). <em>POGZ</em>-associated disorders are most commonly caused by heterozygous loss-of-function (LOF) variants, frequently arising <em>de novo</em>. In this study, we aimed to further this understanding by exploring novel pathogenic variants in the <em>POGZ</em> gene and their impact on the molecular landscape of NDDs. We conducted whole-exome sequencing (WES) in four unrelated Chinese families, each with a member diagnosed with ID. Four heterozygous LOF variants in <em>POGZ</em> were identified, including two frameshift deletions, one canonical splice-site substitution, and one nonsense variant. Parental testing was partially available for three probands and, in each case, was consistent with a <em>de novo</em> origin; parental data were unavailable for the remaining proband. Three out of the four LOF variants identified in this study are novel. Additionally, we undertook RNA sequencing and cohort analysis to delve into the molecular implications of <em>POGZ</em> haploinsufficiency. Aberrant expression was observed in 484 genes across the patients, a subset of which are involved in synaptic formation and function, offering insights into the involved molecular mechanisms. This study broadens the mutational spectrum of <em>POGZ</em>-related NDDs and underscores the crucial role of heterozygous <em>POGZ</em> LOF variants in the pathogenesis of ID and related conditions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150070"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative mitochondrial genomics suggests lack of deep host-associated divergence in Pulex irritans (Arthropoda: Insecta): A one health perspective","authors":"Ying Xun ,&nbsp;Yan-Yan Peng ,&nbsp;Hany M. Elsheikha ,&nbsp;Yuan-Ping Deng ,&nbsp;Yu Zhuo ,&nbsp;Jian-Lei Zou ,&nbsp;Yi-Tian Fu ,&nbsp;Guo-Hua Liu","doi":"10.1016/j.gene.2026.150083","DOIUrl":"10.1016/j.gene.2026.150083","url":null,"abstract":"<div><div>The population structure of the generalist flea <em>Pulex irritans</em>, an important vector for zoonotic pathogens, remains poorly understood, limiting efforts to predict and control disease transmission across the human–animal–environment interface. We performed a comparative mitochondrial (mt) genomic analysis to assess for the presence of deep, host-associated genetic lineages in <em>P. irritans</em>. Complete mt genomes were sequenced from fleas collected from a human and a wild marmot using high-throughput sequencing, and compared with a published dog-derived mt genome from China. The newly assembled mt genomes were approximately 20.4 kb in length and exhibited high conservation, with pairwise nucleotide identities exceeding 98.7% and identical gene organization. Phylogenomic analyses placed all <em>P. irritans</em> isolates within a single, cohesive lineage (Bpp = 1.0; UFBoot = 100), showing no evidence of deep, host-specific substructuring. While the high genetic similarity (&gt;98%) is expected for conspecifics, the absence of deep phylogenetic splitting challenges the hypothesis of ancient, host-specific cryptic species. Ka/Ks ratios for all 13 protein-coding genes were &lt; 1, indicating strong purifying selection. Although limited by sample size, this study provides baseline genomic evidence suggesting that <em>P. irritans</em> likely does not comprise a complex of anciently diverged host-specialized lineages in this region. These findings highlight its potential as a versatile vector and emphasize the need for integrated One Health surveillance strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150083"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel NMD-escaping STAG2 variant associated with syndromic neurodevelopmental delay, growth failure, and distinctive dysmorphism: expanding the phenotype in male patients and literature review","authors":"Firoz Ahmad ,&nbsp;Sapna Sandal ,&nbsp;Alec Correa ,&nbsp;Murali Krishna ,&nbsp;Sowmya Sabnavis ,&nbsp;Syeda Kulsum ,&nbsp;Amisha Shah ,&nbsp;Meenu Angi ,&nbsp;Pooja Chaudhary ,&nbsp;Spandan Chaudhary ,&nbsp;Neeraj Arora","doi":"10.1016/j.gene.2026.150054","DOIUrl":"10.1016/j.gene.2026.150054","url":null,"abstract":"<div><div>We report an 8-year-old male from a consanguineous union presenting with global developmental delay, microcephaly, failure to thrive, and distinctive dysmorphic features (dolichocephaly, triangular face, malar flattening). His elder brother shared similar clinical and dysmorphic findings. The pattern of inheritance within the family (affected male siblings, subtle dysmorphism in mother and consanguinity) prompted consideration of both autosomal recessive and X-linked modes of inheritance. Whole exome sequencing (WES) identified a novel hemizygous <em>STAG2</em> frameshift variant (NM_001042750.2: c.3688_3689del; p.(Thr1230Hisfs*20)) in both brothers, inherited maternally. The variant is predicted to escape nonsense-mediated decay (NMD), potentially explaining survival, as complete <em>STAG2</em> loss of function mutations in hemizygous males are most often embryonic lethal. This represents the first report of NMD-escaping <em>STAG2</em> truncation in living males, expanding the mutational spectrum of STAG2-related disorders. The findings underscore the importance of considering hypomorphic <em>STAG2</em> variants in males with syndromic neurodevelopmental delay and dysmorphism.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150054"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A closed-loop microfluidic platform for enhanced gut organoid maturation via physicochemical control and morphodynamic feedback","authors":"Eric Kwame Owusu ,&nbsp;Donatien Sinzinkayo ,&nbsp;Yue Wang ,&nbsp;Na Liu ,&nbsp;Tao Yue","doi":"10.1016/j.gene.2026.150074","DOIUrl":"10.1016/j.gene.2026.150074","url":null,"abstract":"<div><div>Organoid technology has fundamentally transformed biomedical research, but remains limited by its inability to manipulate the in vivo physicochemical microenvironment. Here, we introduce a platform that bridges engineering and biology by elevating organoid-on-chip culture from a static process to a dynamic, precise science. We present a closed-loop microfluidic system that integrates on-demand CO₂ microreactions for spatiotemporal control of pH and oxygen, along with a novel suite of label-free, image-based morphodynamic sensors. These sensors include the dynamic deformation index (DDI), which quantifies structural stability; the curvature growth indicator (CGI), which tracks morphogenic activity; and the time-integrated shape entropy (TISE), which measures phenotypic variability. Together, the devices monitor the organoid’s state in real time and autonomously maintain physiological homeostasis. We demonstrate that this approach improves organoid health, achieving over 95% viability, reducing hypoxic core formation by 50% compared to static cultures, and enabling robust, physiologically relevant differentiation. Our versatile toolkit enables precise organoid interrogation and control, sets a new standard for intelligent in vitro systems, with significant implications for accelerating the fidelity of disease modelling, drug screening, and personalised medicine.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150074"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of C5AR1 polymorphisms with increased gastric cancer risk: mechanistic insights and therapeutic implications targeting JAK/STAT pathway","authors":"Zhongqi Wang ,&nbsp;Ying Jian ,&nbsp;Xiaomei Jiang ,&nbsp;Hongmei Zhang ,&nbsp;Zhi Zhang ,&nbsp;Xuemei Zhang","doi":"10.1016/j.gene.2026.150086","DOIUrl":"10.1016/j.gene.2026.150086","url":null,"abstract":"<div><div>While the pivotal role of C5a receptor 1 (<em>C5AR1</em>) in cancer immunity is well-established, its specific genetic and functional contributions to gastric cancer (GC) remain elucidated. This study investigates the correlation between <em>C5AR1</em> polymorphisms with GC risk, alongside exploring the underlying molecular mechanisms. Genotyping was conducted utilizing a PCR-based method for identifying restriction fragment length polymorphisms (RFLP). Dual-luciferase reporter assays assessed the transcriptional activity of the rs62128435 and rs8103584 variants. Detecting the impact of <em>C5AR1</em> gene knockdown on cell growth, movement, and spread in NUGC-4 and HGC-27 GC cells by CCK-8, colony formation, and Transwell assays. Western blot was utilized to discover the role of <em>C5AR1</em> in the JAK/STAT signaling pathway. Individuals carrying <em>C5AR1</em> rs62128435 CC and rs8103584 CC genotypes were each associated with elevated GC risk. The <em>C5AR1</em> rs62128435 CC genotype and rs8103584 CC genotype altered GC risk among males, older individuals, smokers, and drinkers. Reporter assays revealed that rs62128435 C and rs8103584 T containing plasmids exhibited higher luciferase activity compared to their counterparts. <em>C5AR1</em> suppressed the proliferation, colony-forming capacity, and migration of GC cells, and reduced the phosphorylation of JAK2 and STAT3, linking <em>C5AR1</em> to JAK/STAT pathway regulation. This study identifies <em>C5AR1</em> polymorphisms as novel risk factors for GC, linking them to regulated transcriptional activity and regulation of JAK/STAT signal. It also highlights the role of gene-environment interactions, such as smoking, alcohol status, in modulating cancer susceptibility. These findings advance understanding of GC pathogenesis and offer a foundation for personalized risk assessment and potential targeted therapies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150086"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}