International Journal of Biological Sciences最新文献_第8页

Mesangial Cells in Diabetic Kidney Disease: From Mechanisms to Therapeutic Implications. 糖尿病肾病系膜细胞：从机制到治疗意义

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-24 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.114907

Li Feng, Yu-Ying Feng, Qian Ren, Ping Fu, Liang Ma

引用次数: 0

TSG6 promotes epithelial-mesenchymal transition and tumor-associated macrophage polarization through Smad2/3 and MAPK signaling by facilitating TSG6-CD44-TGFβR1 or EGFR complex formation. TSG6通过Smad2/3和MAPK信号通路促进TSG6- cd44 - tgf - β r1或EGFR复合物的形成，促进上皮-间质转化和肿瘤相关巨噬细胞极化。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-24 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.115097

Hyun-Ji Oh, Ga-Hong Min, Da-Eun Kim, Sol-Bi Shin, Hyungshin Yim

{"title":"TSG6 promotes epithelial-mesenchymal transition and tumor-associated macrophage polarization through Smad2/3 and MAPK signaling by facilitating TSG6-CD44-TGFβR1 or EGFR complex formation.","authors":"Hyun-Ji Oh, Ga-Hong Min, Da-Eun Kim, Sol-Bi Shin, Hyungshin Yim","doi":"10.7150/ijbs.115097","DOIUrl":"https://doi.org/10.7150/ijbs.115097","url":null,"abstract":"TSG6 is highly expressed during PLK1-induced epithelial-mesenchymal transition (EMT). However, the role of TSG6 in the tumor microenvironment (TME) remains poorly understood. We investigate the function and regulatory mechanisms of TSG6 in immune plasticity within the TME of lung adenocarcinoma (LUAD). The simultaneous high expression of TSG6 and PLK1 in LUAD patients was associated with lower survival rates. TSG6 and CD44 were markedly upregulated during EMT driven by TGF-b or active PLK1 in A549 and HCC827 cells. TSG6 treatment enhanced EMT by increasing N-cadherin and phosphorylated Smad2 levels. TSG6 depletion blocked the effects, which was restored upon TSG6 retreatment. Additionally, TSG6 treatment induced polarization of THP-1 monocytes into M2d tumor-associated macrophages (TAMs). In cocultures of THP-1 monocytes with A549 cells expressing TSG6, M2d-inducing factors in A549 cells and M2d markers in THP-1 cells were upregulated. Immunoprecipitation showed that TSG6 binds CD44, enhancing CD44's interaction with TGFbR or EGFR. In TSG6-treated LUAD cells, both total CD44 and its cleaved intracellular domain increased by activating TGFβR1-Smad2/3 and MAPK-ERK1/2-AP-1 pathways. Thus, TSG6 promotes EMT and M2d-TAMs polarization by activating TGFβR1/Smad and MAPK/ERK pathway through direct interaction between CD44 and TGFβR1 or EGFR.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4701-4718"},"PeriodicalIF":10.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953233","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

Harnessing Natural Products to Surmount Drug Resistance in Gastric Cancer: Mechanisms and Therapeutic Perspectives. 利用天然产物克服胃癌耐药：机制和治疗观点。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.113709

QingShui Wang, Fangqin Xue, Yehuda G Assaraf, Yao Lin

{"title":"Harnessing Natural Products to Surmount Drug Resistance in Gastric Cancer: Mechanisms and Therapeutic Perspectives.","authors":"QingShui Wang, Fangqin Xue, Yehuda G Assaraf, Yao Lin","doi":"10.7150/ijbs.113709","DOIUrl":"10.7150/ijbs.113709","url":null,"abstract":"Gastric cancer remains a major cause of mortality. The current standard of care of gastric cancer is based upon combination chemotherapy comprising platinum, fluoropyrimidines drugs and docetaxel. However, the efficacy of chemotherapy is hindered by intrinsic and acquired drug resistance, resulting in poor patient prognosis. Studies are currently exploring the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most efficacious therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine key biomarkers including for example human epidermal growth factor receptor 2 (HER2) expression, programmed death-ligand 1 (PD-L1) combined positive score (CPS), Claudin 18.2, and microsatellite instability (MSI). Moreover, recent studies have highlighted the potential of natural products as effective agents in surmounting anticancer drug resistance in gastric cancer. These bioactive compounds exhibit various antitumor activities, including induction of apoptosis, inhibition of cell proliferation, modulation of autophagy, and most importantly reversal of distinct multidrug resistance (MDR) modalities. The present review provides a comprehensive analysis of the mechanisms underlying chemoresistance in gastric cancer and explores how natural products can overcome distinct MDR mechanisms. We further discuss the therapeutic potential of combining natural products with established chemotherapeutics and immunotherapy agents to enhance treatment efficacy and reduce adverse effects.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4604-4628"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788843","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

Novel glycoprotein SBSPON suppressed bladder cancer through the AKT signal pathway by inhibiting HSPA5 membrane translocation. 新型糖蛋白SBSPON通过抑制HSPA5膜易位，通过AKT信号通路抑制膀胱癌。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.109973

Beibei Ni, Shi Li, Lan Zhao, Lin Gao, Liya Luo, Junwen Zhang, Xina Xie, Yuqi Zhu, Wei Yang, Shasha Min, Yan Wang, Xianxin Li, Zhiming Cai, John R Speakman, Zesong Li

{"title":"Novel glycoprotein SBSPON suppressed bladder cancer through the AKT signal pathway by inhibiting HSPA5 membrane translocation.","authors":"Beibei Ni, Shi Li, Lan Zhao, Lin Gao, Liya Luo, Junwen Zhang, Xina Xie, Yuqi Zhu, Wei Yang, Shasha Min, Yan Wang, Xianxin Li, Zhiming Cai, John R Speakman, Zesong Li","doi":"10.7150/ijbs.109973","DOIUrl":"10.7150/ijbs.109973","url":null,"abstract":"Bladder cancer poses severe threats to human health due to its aggressive nature and resistance to drug treatment; however, the underlying mechanisms have not been fully investigated. In the present study, we identify SBSPON (Somatomedin B and Thrombospondin Type 1 Domain Containing) as a novel tumor suppressor. The expression of SBSPON was downregulated in bladder cancer and correlated with poor overall survival. SBSPON suppressed the proliferation and migration ability of bladder cancer cells in vitro, and inhibited tumor growth of bladder cancer cells in vivo. Genetic ablation of Sbspon in mice significantly accelerated the progression of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) induced bladder cancer. Mechanistically, SBSPON is a novel HSPA5 binding glycoprotein. SBSPON functioned through binding to HSPA5 and inhibiting its membrane translocation, resulting in an inactivated AKT signaling pathway. More importantly, SBSPON inhibited the cisplatin resistance of bladder cancer cells by reducing the inhibitory effect of HSPA5 on apoptosis. In summary, the novel glycoprotein SBSPON functions as a tumor suppressor and inhibits resistance to cisplatin in bladder cancer. This may provide novel therapeutic strategies for bladder cancer treatment.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4586-4603"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788949","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

The glucose sensor NSUN2-m⁵C modification regulates tumor-immune glucose metabolism reprogramming to drive hepatocellular carcinoma evolution. 葡萄糖传感器NSUN2-m5C的修饰调节肿瘤免疫糖代谢重编程，驱动肝细胞癌的进化。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.115610

Jing He, Boqiang Liu, Weijun Zhao, Hao Shen, Yi Wang, Weiqi Li, Chenqi Jin, Yifan Wang, Xiujun Cai, Liang Shi

{"title":"The glucose sensor NSUN2-m5C modification regulates tumor-immune glucose metabolism reprogramming to drive hepatocellular carcinoma evolution.","authors":"Jing He, Boqiang Liu, Weijun Zhao, Hao Shen, Yi Wang, Weiqi Li, Chenqi Jin, Yifan Wang, Xiujun Cai, Liang Shi","doi":"10.7150/ijbs.115610","DOIUrl":"10.7150/ijbs.115610","url":null,"abstract":"Tumor heterogeneity and the dynamic evolution of tumor immune microenvironment (TIME) contribute to therapeutic resistance and poor clinical prognosis. To elucidate this mechanism, we first established a murine tumor evolution model (TEM) and systematically identified evolutionary core genes demonstrating progressive alterations during evolution. Subsequently, we developed a single-cell TEM through integrative analysis of hepatocellular carcinoma (HCC) clinical specimens (n=10) with external cohorts (n=11), enabling dynamic characterization of tumor-immune interactions during evolution, while addressing ethical challenges associated with obtaining tumor tissues from multiple stages in a single patient. Through TEMs analyses, we identified a contrasting glucose metabolism pattern between malignant cells and CD8+ T cells during tumor evolution. Mechanistically, glucose metabolic dominance triggers NSUN2 upregulation in tumor cells, where this functional RNA methyltransferase stabilizes key glycolytic transcripts (GLUT1, HK2, PFKM) through mRNA methylation. The NSUN2-mediated GLUT1 stabilization enhances the competitive advantage of tumor cells in glucose acquisition, creating a positive feedback loop that accelerates malignancy and exacerbates CD8+ T cell dysfunction. Building on these insights, we designed a dual-targeting strategy combining GLUT1/NSUN2 axis inhibitor WZB117 with PD-L1 blockade, which synergistically suppressed tumor evolution and reversed immunosuppression in preclinical models, suggesting a novel synergistic therapeutic strategy for treatment-resistant HCC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4529-4548"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788953","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

Cancer patient-derived organoids: Novel models for the study of natural products. 癌症患者衍生的类器官：天然产物研究的新模型。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.114373

Shuxin Liu, Ren Zhang, Yachen Liu, Xian Lin, Jian Chen

{"title":"Cancer patient-derived organoids: Novel models for the study of natural products.","authors":"Shuxin Liu, Ren Zhang, Yachen Liu, Xian Lin, Jian Chen","doi":"10.7150/ijbs.114373","DOIUrl":"10.7150/ijbs.114373","url":null,"abstract":"Organoids are multicellular in vitro organ models that are self-organized and derived from stem cells or primary tissues in specific three-dimensional (3D) environments. Cancer patient-derived organoids (CPDOs) retain key characteristics of the original tumor, including genomic, epigenetic, and metabolic profiles, while accurately recapitulating the human tumor microenvironment (TME) - closely mirroring features observed in patient tumors. Compared to traditional cell lines and animal models, CPDOs offer significant advantages, making them increasingly valuable for cancer research and precision medicine. Meanwhile, natural products (NPs) remain a rich and pharmacologically promising source of anticancer drug candidates. In this review, we systematically summarized the important applications of different CPDOs in the efficacy evaluation, drug screening, and mechanism studies of NPs. Moreover, we also discussed the advantages, limitations, and future perspectives of CPDOs, proving valuable insights for researchers and clinicians in this field.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4485-4503"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788871","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

Tissue Factor Pathway Inhibitor 2 Enhances Hepatocellular Carcinoma Chemosensitivity by Activating CCAR2-GADD45A-Mediated DNA Damage Repair. 组织因子通路抑制剂2通过激活ccar2 - gadd45a介导的DNA损伤修复增强肝细胞癌化疗敏感性

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.111142

Hongzhong Zhou, Liwen Zhu, Yajun Zhang, Lichan Chen, Dong-Mei Gou, Haohua Zhang, Rongmao Hua, Jianning Song, Chuanghua Qiu, Fu-Wen Yao, Xiafei Wei, Dayong Gu, Yong Xu

{"title":"Tissue Factor Pathway Inhibitor 2 Enhances Hepatocellular Carcinoma Chemosensitivity by Activating CCAR2-GADD45A-Mediated DNA Damage Repair.","authors":"Hongzhong Zhou, Liwen Zhu, Yajun Zhang, Lichan Chen, Dong-Mei Gou, Haohua Zhang, Rongmao Hua, Jianning Song, Chuanghua Qiu, Fu-Wen Yao, Xiafei Wei, Dayong Gu, Yong Xu","doi":"10.7150/ijbs.111142","DOIUrl":"10.7150/ijbs.111142","url":null,"abstract":"Chemotherapy resistance presents a major challenge in the treatment of hepatocellular carcinoma (HCC), with the underlying molecular mechanisms largely unknown. This study aimed to investigate the role of tissue factor pathway inhibitor 2 (TFPI2) in modulating HCC chemosensitivity. We explored the impact of TFPI2 on sorafenib sensitivity in patient-derived organoids and mouse models using immunofluorescence analysis, chromatin immunoprecipitation, and RNA immunoprecipitation. We observed the downregulation of TFPI2 in HCC, and its deletion in mice (TFPI2HKO) accelerated DEN-induced liver tumorigenesis. Notably, TFPI2 overexpression increased sorafenib sensitivity in HCC organoids and in vivo models. Mechanistic insights indicated that TFPI2 stabilizes the mRNA of growth arrest and DNA damage-inducible alpha (GADD45A) by engaging the cell cycle and apoptosis regulator 2 (CCAR2), promoting GADD45A-mediated DNA damage and inhibiting homologous recombination repair. Furthermore, TFPI2 protects CCAR2 from ubiquitination-induced degradation by associating with the deubiquitinating enzyme BRCC3. We identified polydatin, a resveratrol glycoside, which upregulates TFPI2 and synergistically enhances the chemosensitizing effect of sorafenib in organoids and in vivo. TFPI2 plays a critical role in CCAR2-GADD45A-induced DNA damage repair, providing a strategy to enhance HCC chemosensitivity. Our findings elucidate the molecular intricacies of chemoresistance in HCC and reveal a potential therapeutic target for alleviating this resistance.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4629-4646"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788954","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

New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets. AHR启动子转录协同调控的新认识分子机制和治疗靶点。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.112869

Kenly Wuputra, Chia-Che Ku, Wen-Hung Hsu, Tusty-Jiuan Hsieh, Yi-Chun Tsai, Chih-Yen Chen, Yoshiharu Tanaka, Ying-Chu Lin, Chao-Hung Kuo, Deng-Chyang Wu, Kazunari K Yokoyama

{"title":"New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.","authors":"Kenly Wuputra, Chia-Che Ku, Wen-Hung Hsu, Tusty-Jiuan Hsieh, Yi-Chun Tsai, Chih-Yen Chen, Yoshiharu Tanaka, Ying-Chu Lin, Chao-Hung Kuo, Deng-Chyang Wu, Kazunari K Yokoyama","doi":"10.7150/ijbs.112869","DOIUrl":"10.7150/ijbs.112869","url":null,"abstract":"The aryl hydrocarbon receptor (AHR) plays crucial roles in the control of stress, xenobiotic metabolism, inflammation, and cancer. However, information on the chromatin regulation of ligand-dependent AHR promoter activation is limited. AHR and nuclear factor erythroid 2-related factor 2 (NRF2) signaling are coordinated to maintain the balance of reactive oxygen species (ROS), which is termed the AHR-NRF2 gene battery. Recently, promoter activation of AHR to phase I ligands was reported to be regulated by AHR-NRF2-Jun dimerization protein 2 (JDP2) in a spatiotemporal manner. Tight coupling between phase I and II nuclear transcriptional factor complexes through histone chaperone JDP2 in a time- and space-dependent manner may occur in the chromatin to regulate phase I gene expression. This new mechanism, termed AHR-NRF2-JDP2 gene battery, may facilitate the identification of therapeutics at the reduction of reactive toxic intermediates at the nucleosome level. Identifying the AHR-NRF2-JDP2 gene battery mechanisms will enable the development of novel therapeutics for the risk assessment of oxidative stress/antioxidation, detoxification, ROS, cell death, inflammation, allergies, and cancer.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4504-4528"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788948","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

Novel High-Throughput Screen Identified S100A4 Inhibitors for Anti-Metastatic Therapy. 新型高通量筛选S100A4抑制剂用于抗转移治疗。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.113805

Paul Curtis Schöpe, Nina Heisterkamp, Devin Schütz, Guido Mastrobuoni, Kerstin Putzker, Ulrike Uhrig, Wolfgang Walther, Stefan Kempa, Marc Nazaré, Dennis Kobelt, Ulrike Stein

{"title":"Novel High-Throughput Screen Identified S100A4 Inhibitors for Anti-Metastatic Therapy.","authors":"Paul Curtis Schöpe, Nina Heisterkamp, Devin Schütz, Guido Mastrobuoni, Kerstin Putzker, Ulrike Uhrig, Wolfgang Walther, Stefan Kempa, Marc Nazaré, Dennis Kobelt, Ulrike Stein","doi":"10.7150/ijbs.113805","DOIUrl":"10.7150/ijbs.113805","url":null,"abstract":"Colorectal cancer (CRC) metastasis continues to account for a substantial proportion of cancer-related deaths worldwide. Calcium-binding protein S100A4 is a known executor of CRC metastasis. S100A4 has been correlated to metastasis formation in the past, and therefore pharmaceutical intervention reduces the metastatic phenotype. Herein, a high-throughput screen (HTS) of 105,600 compounds from the EMBL screening library using an S100A4 promoter-driven luciferase construct transfected into HCT116 cells identified novel compounds for S100A4 transcriptional inhibition. The most promising inhibitors identified were tested for S100A4 transcriptional inhibition, their impact on wound healing, migration, proliferation and viability of cancer cells. Subsequently, the leading candidate E12 was tested in vivo in a xenograft mouse model (HCT116/CMVp- Luc). After several testing rounds, E12 a 2-(4-fluorobenzenesulfonamido)benzamide-based compound showed the strongest inhibition of S100A4 expression at mRNA (EC50 < 1 µM; 48 h) and protein level and concomitant restriction of metastatic abilities in two CRC cell lines with a tolerable viability reduction. In vivo, a reduction in metastasis formation was demonstrated, displayed by reduced overall bioluminescence of tumors and human satellite DNA in the liver of treated mice. This study exhibited E12's promising potential for S100A4 targeted metastasis inhibition therapy to improve the outcome of metastasized CRC patients.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4683-4700"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788950","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

LncRNA SLC7A11AR promotes lung adenocarcinoma progression by inhibiting ferroptosis via promoting SLC7A11 expression. LncRNA SLC7A11AR通过促进SLC7A11表达抑制铁下垂促进肺腺癌进展。

IF 1 2区生物学

International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.112233

Haoqing Zhai, Xudong Xiang, Jun Pu, Xiaoqun Niu, Jie Gao, Dengcai Mu, Jia Du, Yao Li, Laihao Qu, Baiyang Liu, Yongbin Chen, Cuiping Yang

{"title":"LncRNA SLC7A11AR promotes lung adenocarcinoma progression by inhibiting ferroptosis via promoting SLC7A11 expression.","authors":"Haoqing Zhai, Xudong Xiang, Jun Pu, Xiaoqun Niu, Jie Gao, Dengcai Mu, Jia Du, Yao Li, Laihao Qu, Baiyang Liu, Yongbin Chen, Cuiping Yang","doi":"10.7150/ijbs.112233","DOIUrl":"10.7150/ijbs.112233","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is a prevalent classification of human lung cancer with a variety of clinical pathological features. Several key factors and associated signaling pathways have played pivotal roles in the progression of NSCLC and serve as potential therapeutic targets. However, the therapeutic efficacy is still limited, and novel biomarkers and key regulators are inevitable. We found a human-specific long non-coding RNA (lncRNA, ENST00000504300) induced by the inflammatory pathway, termed SLC7A11AR (SLC7A11 associated lncRNA), which was highly expressed in lung adenocarcinoma (LUAD) cell lines but not in lung squamous cell carcinoma (LUSC). Our research showed that higher SLC7A11AR expression correlates with a poorer clinical prognosis. Depleting SLC7A11AR restrains tumor cell proliferation, migration, and xenograft tumor formation by promoting ferroptosis. Bioinformatic analysis and dual luciferase reporter assays revealed that SLC7A11AR binds directly to miR-150-5p, weakening the inhibition on its downstream target SLC7A11, a key ferroptosis inhibitor in NSCLC. In cancerous tissues, SLC7A11AR was upregulated, while miR-150-5p was downregulated compared to control tissues. Enforced miR-150-5p expression inhibited tumor growth. Moreover, ASOs against SLC7A11AR alone or with a ferroptosis agonist significantly suppressed tumor progression. Our results suggest that the SLC7A11AR/miR-150-5p/SLC7A11 axis plays an oncogenic role in LUAD development and has the potential to be novel therapeutic targets, presenting new opportunities for LUAD treatment in the future.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4549-4566"},"PeriodicalIF":10.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788945","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