International Journal of Biological Sciences最新文献

HOTAIR Promotes Prostate Cancer Progression by facilitating CDK9-Pol II Association and Transcriptional Elongation. HOTAIR通过促进CDK9-Pol II关联和转录延伸促进前列腺癌进展。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-10 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.134766

Yuyang Qian, Bo Wang, Guangsong Su, Peng Li, Zhenhao Zhao, Yuan Jiang, Lei Zhang, Zhongfang Zhao, Mulin Jun Li, Jiandang Shi, Dandan Huang, Wange Lu

{"title":"HOTAIR Promotes Prostate Cancer Progression by facilitating CDK9-Pol II Association and Transcriptional Elongation.","authors":"Yuyang Qian, Bo Wang, Guangsong Su, Peng Li, Zhenhao Zhao, Yuan Jiang, Lei Zhang, Zhongfang Zhao, Mulin Jun Li, Jiandang Shi, Dandan Huang, Wange Lu","doi":"10.7150/ijbs.134766","DOIUrl":"10.7150/ijbs.134766","url":null,"abstract":"Previous research has predominantly focused on the regulatory role of lncRNA HOTAIR in gene silencing by interacting with the Polycomb repressive complex 2 (PRC2), but its direct role as a transcriptional activator remains less well characterized. Here, our study reveals a novel regulatory mechanism of HOTAIR, which facilitates prostate cancer (PCa) progression by enhancing transcription elongation. Integrating ChIRP-seq, RNA-seq, and ChIP-seq, we found that HOTAIR co-localizes with AR and facilitates the interaction between CDK9 and Pol II. This function requires the 1-442 nt region and intact RNA, as deletion or RNase treatment disrupts the interaction. Re-expression of full-length HOTAIR, but not the deletion mutant, restores nascent transcription of target genes; conversely, CDK9 inhibition suppresses this elongation effect. We identified MMP14 and TNFAIP2 as functional downstream targets; ectopic expression of either rescues colony formation and invasive migration upon HOTAIR depletion. HOTAIR knockdown reduced Ser2P and Ser5P signals at target loci, yet RNA pull-down showed no direct binding to Pol II Ser5P, implying that any effect on initiation is indirect. This elongation activity operates in both AR-positive and AR-negative cells, with AR acting as a context-specific recruiter. Collectively, these findings support a model in which HOTAIR functions as an elongation activator and suggest potential therapeutic targets in prostate cancer.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"8054-8073"},"PeriodicalIF":11.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial, single-nucleus and pathological profiling of the invasive front in early hepatocellular carcinoma for characterizing specific leading-edge cell niche and improving recurrence modeling. 早期肝细胞癌侵袭前沿的空间、单核和病理分析，以表征特定的前沿细胞生态位和改进复发模型。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-10 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.137262

Xicheng Wang, Xiaolan Mu, Yong Fu, Wei Dong, Wenfeng Lu, Xiuhua Li, Yanxiang Song, Changcheng Liu, Baoju Hou, Haibin Zhang, Xiong Chen, Yongchao Cai, Zhiying He

{"title":"Spatial, single-nucleus and pathological profiling of the invasive front in early hepatocellular carcinoma for characterizing specific leading-edge cell niche and improving recurrence modeling.","authors":"Xicheng Wang, Xiaolan Mu, Yong Fu, Wei Dong, Wenfeng Lu, Xiuhua Li, Yanxiang Song, Changcheng Liu, Baoju Hou, Haibin Zhang, Xiong Chen, Yongchao Cai, Zhiying He","doi":"10.7150/ijbs.137262","DOIUrl":"10.7150/ijbs.137262","url":null,"abstract":"The tumor leading edge (TLE) is a critical region where tumor cells interact with the microenvironment to drive invasion and metastasis; however, its cellular architecture in early hepatocellular carcinoma (HCC) remains poorly understood. Here, we integrated single-nucleus RNA-seq (snRNA-seq), spatial transcriptomics, and computational pathology to investigate TLE in early HCC. We annotated 35 cell subpopulations and identified STMN1-high tumor cells as a key malignant subset enriched at the invasive front, interacting with Treg, plasma B, LAMP3⁺ dendritic cells and SPP1⁺ macrophages. Spatial analysis revealed three co-localized cell pairs-(SPP1⁺ macrophages co-localized with Tip-like and inflammatory endothelial cells), (LAMP3⁺ DCs co-localized with naive T cells), and (plasma B cells co-localized with cancer-associated fibroblasts)-forming a leading-edge tumor microenvironment (L-TME) niche associated with early relapse. We developed an L-TME-related machine-learning benchmark framework incorporating 71 imaging features (65 deep-learning + 6 pathological) based on the snRNA-seq, spatial transcriptomics and pathomics. The pathology model achieved robust performance (mean C-index=0.77) and successfully predicted the recurrence of early HCC (log-rank p < 0.05) in TCGA (n=147) and an independent in-house cohort (n=123). This study delineates the TLE cellular ecosystem of early HCC, defines a spatially coordinated immunosuppressive L-TME niche, and provides a clinically applicable predictive tool for postoperative recurrence. Integrating multi-omics with computational pathology deepens our understanding of early HCC metastasis and offers insights into improved prognostication and therapeutic strategies.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"8090-8118"},"PeriodicalIF":11.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disrupted Estrogen Homeostasis Drives Female-Specific Depressive-Like and Anxiety-Like Behaviors via Convergent ERα Downregulation in the Ventral Hippocampus. 雌激素稳态紊乱通过腹侧海马ERα趋同下调驱动女性特异性抑郁样和焦虑样行为

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-10 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.137575

Zhengyang Wang, Yikun Ren, Feiran Cheng, Peng Wang, Bangmin Yin, Yajie Xiang, Ying Yu, Dan Liu, Xinyi Yang, Peng Xie

{"title":"Disrupted Estrogen Homeostasis Drives Female-Specific Depressive-Like and Anxiety-Like Behaviors via Convergent ERα Downregulation in the Ventral Hippocampus.","authors":"Zhengyang Wang, Yikun Ren, Feiran Cheng, Peng Wang, Bangmin Yin, Yajie Xiang, Ying Yu, Dan Liu, Xinyi Yang, Peng Xie","doi":"10.7150/ijbs.137575","DOIUrl":"10.7150/ijbs.137575","url":null,"abstract":"Although depression exhibits prominent sex differences, mechanisms linking estrogen fluctuations to this vulnerability remain unclear. Here, we reveal that disrupted estrogen homeostasis induces depressive- and anxiety-like behaviors via convergent downregulation of estrogen receptor alpha (ERα) and subsequent neuroinflammation in the female ventral hippocampus (vHPC). In humans (n=6,481), serum estradiol (E2) showed a U-shaped association with depression, increasing risk at both extremes. In mice, while chronic restraint stress (CRS) induced depressive-like behaviors across sexes, it selectively triggered E2 deficiency, anxiety-like behaviors, and decreased vHPC ERα (but not ERβ) in females. Therefore, focusing on females, both supraphysiological E2 (sE2)-induced elevation and CRS-induced E2 deficiency produced depressive- and anxiety-like behaviors converging on vHPC ERα downregulation. Cross-species transcriptomics and multi-omics revealed global concordance between female major depressive disorder (MDD) and both mouse models, identifying ERα as a top upstream regulator associated with neuroinflammation, lipid dysregulation, and synaptic dysfunction. Pharmacological inhibition of ERα exacerbated depressive- and anxiety-like behaviors and neuroinflammation under subthreshold CRS, whereas vHPC ERα overexpression rescued CRS-induced behavioral deficits and neuroinflammatory responses. Integrating human MDD GWAS and PsyGeNET datasets supported this pathway's genetic and clinical relevance. Collectively, we identify vHPC ERα as a unifying therapeutic target for female depression.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"8074-8089"},"PeriodicalIF":11.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

USP10 stabilizes FOXM1 through KAT5-mediated acetylation to suppress cell senescence and promote melanoma malignant progression. USP10通过kat5介导的乙酰化作用稳定FOXM1，抑制细胞衰老，促进黑色素瘤恶性进展。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-10 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.136120

Zhiyuan Qiu, Chenglian Sun, Juan Wang, Dapeng Liang, Shang Wang, Lili Tian, Tongde Du, Chuanchun Han

{"title":"USP10 stabilizes FOXM1 through KAT5-mediated acetylation to suppress cell senescence and promote melanoma malignant progression.","authors":"Zhiyuan Qiu, Chenglian Sun, Juan Wang, Dapeng Liang, Shang Wang, Lili Tian, Tongde Du, Chuanchun Han","doi":"10.7150/ijbs.136120","DOIUrl":"10.7150/ijbs.136120","url":null,"abstract":"The ubiquitin signaling cascade plays a pivotal role in multiple cancer types, yet its role in melanoma progression remains incompletely elucidated. An unbiased and systematic analysis indicates that Ubiquitin-specific peptidase 10 (USP10), a member of USP gene family, was top priority prognostic signature for primary and metastatic melanoma progression-free survival and silencing USP10 markedly impairs the growth and metastatic potential of melanoma cells. We further uncover Forkhead box M1 (FOXM1) as a novel substrate of USP10. USP10 directly binds to FOXM1 and removes ubiquitin chains, thereby enhancing FOXM1 protein stability and driving melanoma progression. Notably, the lysine acetyltransferase KAT5 acetylates FOXM1 at residues K422 and K440, which strengthens the interaction between FOXM1 and USP10, facilitating deubiquitination and subsequent stabilization of FOXM1. Additionally, loss of either USP10 or FOXM1 suppresses the expression of the downstream target Telomerase reverse transcriptase (TERT), triggering cellular senescence. Importantly, we identify Golvatinib, as a novel inhibitor of USP10 that effectively curbs melanoma malignancy in both cellular and animal models. Taken together, these findings highlight the pro-tumorigenic role of USP10 in melanoma and suggest that disrupting the USP10/FOXM1 signaling axis could represent a viable therapeutic approach for treating this aggressive cancer.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"8029-8052"},"PeriodicalIF":11.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZIP1-dependent lymphatic adaptations facilitate lymph node metastasis of pancreatic cancer. zip1依赖性淋巴适应促进胰腺癌淋巴结转移。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-10 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.134874

Ruoyang Chen, Kaili Zhang, Jiajia Wan, Yuanyuan Yang, Linlin Wang, Xiangjing Miao, Qingqing Fang, Yu Hu, Xixi Duan, Xiaohan Lou, Xiaohan Yao, Anqi Li, Linyu Zhu, Zhihai Qin, Chen Ni

{"title":"ZIP1-dependent lymphatic adaptations facilitate lymph node metastasis of pancreatic cancer.","authors":"Ruoyang Chen, Kaili Zhang, Jiajia Wan, Yuanyuan Yang, Linlin Wang, Xiangjing Miao, Qingqing Fang, Yu Hu, Xixi Duan, Xiaohan Lou, Xiaohan Yao, Anqi Li, Linyu Zhu, Zhihai Qin, Chen Ni","doi":"10.7150/ijbs.134874","DOIUrl":"10.7150/ijbs.134874","url":null,"abstract":"Tumor disseminates through lymphatic vessels to form lymph node (LN) metastasis, which requires lymphatic adaptations. However, it remains largely unknown how lymphatic vessels adapt to the stimuli causing LN metastasis of pancreatic cancer. Zinc dyshomeostasis has been observed in various tumors, including pancreatic cancer. We hypothesize that lymphatic vessels actively adapt to zinc imbalance, and examine lymphatic functions and LN metastasis of transplanted pancreatic cancer in zinc transporter ZIP1 deficient mice. The results show that ZIP1 is required for lymphatic glycolysis and junctional adaptations that facilitate LN metastasis of pancreatic cancer. In Zip1-/- mice, the opening of lymphatic barrier and LN metastasis of pancreatic cancer are both mitigated. Inhibition of ZIP1 decreases Zn2+ influx and increases tight junction protein Claudin-5 in lymphatic endothelial cells, thereby suppressing tumor trans-endothelial migration. Mechanistically, ZIP1 promotes lymphatic glycolysis to produce lactic acids which impair Claudin-5 expression. Furthermore, in lymphatic-specific Zip1 knockout mice, lymphatic barrier is tightened and LN metastases are reduced. Importantly, ZIP1+ lymphatics are positively associated with LN metastasis of human pancreatic cancer. Taken together, these findings suggest that ZIP1-dependent metabolic and junctional adaptations in lymphatics accelerate LN metastasis of pancreatic cancer, providing potential therapeutic targets for pancreatic cancer metastasis.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"8119-8138"},"PeriodicalIF":11.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Triptolide in Combination with the Gli1 Inhibitor GANT61 Eradicates Anaplastic Thyroid Cancer by Suppressing Cancer Stem Cell Self-Renewal and Enhancing Apoptosis and Pyroptosis. 雷公藤甲素联合Gli1抑制剂GANT61通过抑制癌干细胞自我更新和促进细胞凋亡和焦亡来根除间变性甲状腺癌。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-10 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.131070

Yuqing Zhao, Yue Zhu, Shuying Zhong, Penggang Liu, Wei Li, Xiaoyun Mao, Xiulong Xu

{"title":"Triptolide in Combination with the Gli1 Inhibitor GANT61 Eradicates Anaplastic Thyroid Cancer by Suppressing Cancer Stem Cell Self-Renewal and Enhancing Apoptosis and Pyroptosis.","authors":"Yuqing Zhao, Yue Zhu, Shuying Zhong, Penggang Liu, Wei Li, Xiaoyun Mao, Xiulong Xu","doi":"10.7150/ijbs.131070","DOIUrl":"10.7150/ijbs.131070","url":null,"abstract":"Anaplastic thyroid cancer (ATC) is a lethal malignancy characterized by therapy resistance and rapid recurrence, driven in part by a population of thyroid cancer stem cells (CSCs). While the Gli1 inhibitor GANT61 targets CSC self-renewal, its efficacy is limited by compensatory activation of the pro-survival TAK1-AMPK pathway. Our present study aims to determine whether triptolide (TPL), a natural compound that inhibits TAK1 and induces reactive oxygen species (ROS), can overcome this resistance and achieve a synergistic anticancer effect when use with GANT61. Here, we report that TPL blocked GANT61-induced TAK1-AMPK activation. TPL alone effectively inhibited the proliferation of two ATC cell lines (8505C and SW1736) and achieved a synergistic anti-proliferative effect when used in combination with GANT61. Consistently, TPL alone effectively suppressed SW1736 xenograft tumor growth but, when used in combination with GANT61, prevented tumor recurrence. TPL in combination with GANT61 synergistically inhibited thyroid CSC self-renewal and induced apoptosis and pyroptosis. Mechanistically, TPL blocked GANT61-mediated activation of the TAK1-AMPK axis and synergistically induced ROS generation, which potentiated pyroptotic activity of Gasdermin D and E (GSDMD/E). This was confirmed by the evidence that TAK1 and AMPK inhibition by gene knockout or their specific inhibitors enhanced apoptotic and pyroptotic activity of GANT61, whereas ROS scavenge blocked apoptosis and pyroptosis induced by TPL and/or GANT61. Taken together, our study provides mechanistic insights into how TPL overcomes a key resistance pathway in CSC target therapy and suggests that the TPL-GANT61 combination could be a promising strategy to eradicate ATC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"8008-8028"},"PeriodicalIF":11.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioactive Constituents of Ginseng in Cancer Therapy: Molecular Mechanisms, Translational Potential, and Advanced Delivery Strategies. 人参在癌症治疗中的生物活性成分：分子机制、转化潜力和先进的递送策略。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-03 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.136955

Jia-Hui Li, Yan-Fang Xian, De-Wen Liu, Hong-Yuan Li, Wei Li

{"title":"Bioactive Constituents of Ginseng in Cancer Therapy: Molecular Mechanisms, Translational Potential, and Advanced Delivery Strategies.","authors":"Jia-Hui Li, Yan-Fang Xian, De-Wen Liu, Hong-Yuan Li, Wei Li","doi":"10.7150/ijbs.136955","DOIUrl":"10.7150/ijbs.136955","url":null,"abstract":"Cancer remains a major global health challenge, highlighting the urgent need to develop safer and more effective therapeutic drugs. Ginseng (Panax ginseng C.A. Mey.), as a medicinal plant widely used in traditional Chinese medicine, has attracted much attention for its extensive anticancer potential and a variety of biologically active ingredients (especially ginseng saponins and polysaccharides). This article reviews the latest research progress on the pharmacological activity and molecular mechanism of ginseng extract in cancer treatment, focusing on its inhibition of tumor growth, inducing cell apoptosis, inhibiting epithelial-mesenchymal transformation and metastasis, reshaping the tumor microenvironment, enhancing antitumor immunity, regulating metabolic reprogramming, and regulating epigenetics. In addition, this article also explores their potential to overcome multi-drug resistance and enhance the efficacy of traditional chemotherapy drugs. In recent years, a variety of drug delivery systems, including polymer nanoparticles, lipids, and micelles, have been developed to improve the bioavailability, stability, and tumor targeting of these compounds. This article also focuses on the current progress and challenges in clinical transformation, especially in the development and application of ginseng saponin preparations. In a word, this article provides a comprehensive review of ginseng-derived drugs from the perspective of pharmacology and translational medicine, and looks forward to the future direction of their reasonable development in cancer treatment.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7800-7826"},"PeriodicalIF":11.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Histone demethylase KDM4A promotes endometrial cancer progression through an ERRγ-associated cell-cycle regulatory axis. 组蛋白去甲基化酶KDM4A通过erγ相关的细胞周期调节轴促进子宫内膜癌的进展。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-03 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.133986

Junfeng Chen, Xiaoli Wen, Donghai Zhang, Mengyue Zhu, Hong Zhou, Yiran Li, Xiaoping Wan

{"title":"Histone demethylase KDM4A promotes endometrial cancer progression through an ERRγ-associated cell-cycle regulatory axis.","authors":"Junfeng Chen, Xiaoli Wen, Donghai Zhang, Mengyue Zhu, Hong Zhou, Yiran Li, Xiaoping Wan","doi":"10.7150/ijbs.133986","DOIUrl":"10.7150/ijbs.133986","url":null,"abstract":"Endometrial cancer (EC) is driven by complex genetic and epigenetic alterations, but the specific chromatin-dependent mechanisms that sustain malignant proliferation remain incompletely understood. In this study, we found that lysine demethylase 4A (KDM4A) was upregulated in EC and promoted cell proliferation, migration, and invasion, accompanied by increased estrogen-related receptor gamma (ERRγ) expression. Mechanistically, KDM4A promoted ERRγ expression in association with reduced enrichment of the repressive H3K9me3 modification at the ESRRG promoter, suggesting that KDM4A may facilitate ESRRG transcription by attenuating H3K9me3-associated repression. Functionally, ERRγ acted as a downstream mediator associated with increased CDK1 transcription and elevated CDK1 and Cyclin B1 protein expression. These findings suggest that the KDM4A-ERRγ axis contributes to G2/M-phase regulation and EC cell proliferation. Importantly, treatment with the KDM4-family inhibitor QC6352 significantly suppressed EC cell growth in vitro and reduced xenograft tumor growth in vivo. These findings support a model in which KDM4A-associated reduction of H3K9me3 enrichment at the ESRRG promoter contributes to ERRγ upregulation and altered cell-cycle regulation in EC cells. Furthermore, these findings provide preliminary preclinical support for further investigation of KDM4-family inhibition as a potential therapeutic approach in EC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7827-7844"},"PeriodicalIF":11.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hippocampal NLRP3 Inflammasome Drives Anxiety- and Depressive-Like Behaviors Following Drug-Induced Liver Injury. 海马NLRP3炎性体驱动药物性肝损伤后的焦虑和抑郁样行为。

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-03 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.128620

Hao Zhang, Jia-Lu Zhuang, Rui Ma, Sheng Wang, Jing Huang, Hui-Xia Yang, Ming-Ming Hu, Xiao-Li Wei, Hai-Yuan Shen, Hui Fang, Wen-Ning Wu, Hua Wang

{"title":"Hippocampal NLRP3 Inflammasome Drives Anxiety- and Depressive-Like Behaviors Following Drug-Induced Liver Injury.","authors":"Hao Zhang, Jia-Lu Zhuang, Rui Ma, Sheng Wang, Jing Huang, Hui-Xia Yang, Ming-Ming Hu, Xiao-Li Wei, Hai-Yuan Shen, Hui Fang, Wen-Ning Wu, Hua Wang","doi":"10.7150/ijbs.128620","DOIUrl":"10.7150/ijbs.128620","url":null,"abstract":"Drug-induced liver injury (DILI) is a considerable and potentially severe adverse reaction to medications. As drug abuse continues to rise, managing drug-induced liver toxicity has become a considerable challenge for clinicians. Depression is a chronic neurological disorder with a rising incidence globally in recent years, adding to the overall societal burden. Numerous clinical studies have suggested a link between DILI and mental illnesses, with inflammation potentially playing a mediating role. However, the exact mechanisms remain unclear. Here, we established a mouse model of DILI through acetaminophen (APAP) exposure and assessed the correlation between mental disorder and NLRP3 inflammasome. We found that DILI mice exhibited anxiety- and depressive-like behaviors, along with disrupted blood-brain barrier integrity and a significant increase in hippocampal NLRP3 inflammasome levels. Nlrp3 knockout or hippocampal Nlrp3 knockdown ameliorated DILI-induced anxiety- and depressive-like behaviors. Moreover, N-acetylcysteine, an agent against APAP-induced hepatotoxicity, inhibited NLRP3 inflammasome activation and alleviated anxiety- and depressive-like behaviors in DILI mice. These results indicate that the NLRP3 inflammasome might be a promising target for the treatment of patients with DILI who experience comorbid anxiety and depression.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7782-7799"},"PeriodicalIF":11.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Iron Regulatory Protein 2 in Tumor-associated Macrophages Activates Antitumor Immunity in NSCLC via Modulating SphK1-PD-L1 Axis. 靶向肿瘤相关巨噬细胞中的铁调节蛋白2通过调节SphK1-PD-L1轴激活非小细胞肺癌的抗肿瘤免疫

IF 11.7 2区生物学

International Journal of Biological Sciences Pub Date : 2026-09-03 eCollection Date: 2026-01-01 DOI: 10.7150/ijbs.130591

Jiawen Ding, Qinpei Cheng, Chen Cheng, Ying Mei, Liu Yang, Peilin Chen, Lei Zheng, Suhua Zhu, Kaikai Shen, Kuanyu Li, Tangfeng Lv

{"title":"Targeting Iron Regulatory Protein 2 in Tumor-associated Macrophages Activates Antitumor Immunity in NSCLC via Modulating SphK1-PD-L1 Axis.","authors":"Jiawen Ding, Qinpei Cheng, Chen Cheng, Ying Mei, Liu Yang, Peilin Chen, Lei Zheng, Suhua Zhu, Kaikai Shen, Kuanyu Li, Tangfeng Lv","doi":"10.7150/ijbs.130591","DOIUrl":"10.7150/ijbs.130591","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. As a predominant immune cell population in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play a critical role in tumor progression and resistance to immune checkpoint inhibitors (ICIs). TAMs can promote either antitumor immunity or immunosuppression depending on their polarization status. Iron regulatory protein 2 (IRP2) is a key regulator of intracellular iron homeostasis and has been reported to be upregulated in several tumor types. However, the role of IRP2 in the TME remains unclear. This study revealed the previously unrecognized role of IRP2 in NSCLC progression and explored its potential as a TAM-directed therapeutic target linked to programmed death-ligand 1 (PD-L1) regulation. We found that IRP2 skewed TAMs toward an immunosuppressive state that promoted tumor cell proliferation and migration, and limited apoptosis. Furthermore, IRP2 may sustain PD-L1 expression in TAMs by limiting sphingosine kinase 1 (SphK1)-associated lysosomal degradation. In conclusion, our findings identify IRP2-dependent maintenance of the immunosuppressive TAM phenotype as a promising therapeutic target in NSCLC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7928-7947"},"PeriodicalIF":11.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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