Cell Cycle最新文献_第2页

NSUN2-mediated m5C modification of PGK1 mRNA promotes cell growth, invasion, stemness and glycolysis in gastric cancer. nsun2介导的m5C修饰PGK1 mRNA促进胃癌细胞生长、侵袭、干性和糖酵解。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-07-01 Epub Date: 2025-08-12 DOI: 10.1080/15384101.2025.2544829

Songjie Liu, Bing Xu, Jian Zhao

{"title":"NSUN2-mediated m5C modification of PGK1 mRNA promotes cell growth, invasion, stemness and glycolysis in gastric cancer.","authors":"Songjie Liu, Bing Xu, Jian Zhao","doi":"10.1080/15384101.2025.2544829","DOIUrl":"10.1080/15384101.2025.2544829","url":null,"abstract":"To explore functions and mechanisms in gastric cancer (GC) progression. The mRNA and protein levels of NSUN2 and phosphoglycerate kinase 1 (PGK1) were determined by qRT-PCR and western blot. Cell proliferation, apoptosis, invasion and stemness were examined using CCK8 assay, EdU assay, flow cytometry, transwell assay and sphere formation assay. Cell glycolysis was evaluated by detecting glucose consumption, lactate production and ATP/ADP ratio. The interaction between PGK1 and NSUN2 or YBX1 was evaluated using MeRIP assay or RIP assay. Actinomycin D treatment assay was used to detect the effect of NSUN2 or YBX1 knockdown on PGK1 mRNA stability. The protein levels of p-PI3K/PI3K and p-AKT/AKT were tested by western blot. Animal study was performed to confirm the effect of NSUN2/PGK1 axis on GC tumorigenesis. NSUN2 was confirmed to be upregulated in GC tissues and cells. NSUN2 silencing could repress GC cell growth, invasion, stemness and glycolysis. NSUN2 enhanced PGK1 mRNA stability through promoting its m5C modification, and this modification could be recognized by YBX1. Besides, PGK1 overexpression reversed the inhibitory effect of NSUN2 knockdown on GC cell growth, invasion, stemness and glycolysis. In addition, NSUN2/PGK1 axis increased the activity of PI3K/AKT pathway. Animal study revealed that interference of NSUN2 reduced GC tumorigenesis via inactivating the PGK1/PI3K/AKT pathway. NSUN2/PGK1 axis might play a vital role in GC development.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"283-295"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820675","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}

引用次数: 0

METTL3-mediated circ_0003998 serves as oncogene in non-small cell lung cancer through regulating miR-330-5p/CXCL3 axis. mettl3介导的circ_0003998通过调控miR-330-5p/CXCL3轴在非小细胞肺癌中起致癌基因作用。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-07-01 Epub Date: 2025-08-08 DOI: 10.1080/15384101.2025.2540139

Guanhua Liu, Zhilong Li, Chaowei Tang

{"title":"METTL3-mediated circ_0003998 serves as oncogene in non-small cell lung cancer through regulating miR-330-5p/CXCL3 axis.","authors":"Guanhua Liu, Zhilong Li, Chaowei Tang","doi":"10.1080/15384101.2025.2540139","DOIUrl":"10.1080/15384101.2025.2540139","url":null,"abstract":"Circular RNA (circRNA) is involved in the occurrence of many cancers. Nonetheless, the mechanism of circ_0003998 in non-small cell lung cancer (NSCLC) needs to be studied in depth. Real-time quantitative PCR (RT-qPCR) was carried out to check the expression of circ_0003998, microRNA-330-5p (miR-330-5p), chemokine (C-X-C motif) ligand 3 (CXCL3) and methyltransferase-3 (METTL3) in NSCLC tissues and cells. CXCL3, Vimentin and E-cadherin protein levels were measured by western blot. The functions of circ_0003998 in NSCLC cell proliferation, apoptosis, angiogenesis, migration and invasion were tested by clone formation assay, flow cytometry, tube formation assay, wound healing assay, and transwell assay in vitro. The dual-luciferase reporter assay was made to verify the relationship between miR-330-5p and circ_0003998 or CXCL3. Finally, animal experiment was made to further research the function of circ_0003998 on tumor formation in vivo. The interaction between circ_0003998 and METTL3 was analyzed by RNA Immunoprecipitation (RIP) assay, methylated RNA Immunoprecipitation (MeRIP) assay and dual-luciferase reporter assay. In NSCLC tissue and cells, circ_0003998 was markedly overexpressed. Circ_0003998 suppression inhibited NSCLC cell growth, angiogenesis, migration and invasion. Circ_0003998 sponged miR-330-5p, and miR-330-5p inhibitor could reverse the suppression effect of circ_0003998 knockdown on NSCLC cell behaviors. CXCL3 was a downstream target gene of miR-330-5p, and CXCL3 overexpression also reversed the suppressive effect of miR-330-5p on NSCLC cell behaviors. Interference of circ_0003998 reduced NSCLC tumorigenesis by regulating miR-330-5p/CXCL3 axis. Also, METTL3 promoted the expression of circ_0003998 by m6A modification. METTL3-modified circ_0003998 promoted NSCLC cell malignancy through miR-330-5p/CXCL3 axis, suggesting that circ_0003998 might be a new treatment strategy for NSCLC.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"268-282"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798296","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}

引用次数: 0

Unfolded protein response complexity in gynecological tumor dynamics: therapeutic challenges and future perspectives. 未折叠蛋白反应复杂性在妇科肿瘤动力学：治疗挑战和未来展望。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-07-01 Epub Date: 2025-08-07 DOI: 10.1080/15384101.2025.2543091

Vandana Yadav, Aruna Sivaram, Renu Vyas

引用次数: 0

RNF220 enhances USP22 to promote cell growth, metastasis and stemness in hepatocellular carcinoma by activating the Akt pathway. RNF220通过激活Akt通路，增强USP22促进肝癌细胞生长、转移和干细胞。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-07-01 Epub Date: 2025-08-26 DOI: 10.1080/15384101.2025.2550448

Weijie Xiong, Hongyu Xu, Yamao Li, Yin Wang, Lang He

{"title":"RNF220 enhances USP22 to promote cell growth, metastasis and stemness in hepatocellular carcinoma by activating the Akt pathway.","authors":"Weijie Xiong, Hongyu Xu, Yamao Li, Yin Wang, Lang He","doi":"10.1080/15384101.2025.2550448","DOIUrl":"10.1080/15384101.2025.2550448","url":null,"abstract":"Hepatocellular carcinoma (HCC) is characterized by high metastatic potential and poor prognosis. Ring finger protein 220 (RNF220) has been implicated in tumorigenesis across various cancers; however, its role and associated regulatory mechanisms in HCC remain unclear. In this study, analysis of The Cancer Genome Atlas (TCGA) database revealed that RNF220 expression was significantly elevated in liver hepatocellular carcinoma (LIHC) tissues and was associated with poor prognosis. Further experiments confirmed the upregulation of RNF220 mRNA and protein in HCC tissues. Functional assays demonstrated that RNF220 overexpression promoted cell proliferation, migration and stemness, whereas RNF220 knockdown suppressed these processes in HCC cells. Mechanistically, RNF220 enhanced ubiquitin-specific protease 22 (USP22) expression, leading to activation of the protein kinase B (Akt) pathway. Furthermore, the knockdown of RNF220 inhibited HCC progression, an effect that could be reversed by SC79 (an Akt activator), an Akt activator. In vivo experiments further confirmed that RNF220 aggravated tumor growth and metastasis. In summary, these findings indicate that RNF220 promotes HCC progression by regulating USP22 and activating the Akt pathway, suggesting that RNF220 may serve as a potential biomarker and therapeutic target for HCC.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"24 13-16","pages":"316-328"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039147","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}

引用次数: 0

Pan-cancer landscape of basement membrane: multi-omics research and single-cell sequencing validation. 基底膜泛癌景观：多组学研究和单细胞测序验证。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-05-01 Epub Date: 2025-08-13 DOI: 10.1080/15384101.2025.2539645

Yi Tang, Qiuhuan Zhang, Zhuoer Yuan, De Yin, Shengyue Zhang, Yucao Sun, Chong-de Mo, Zhenyong Tang, Jiehua Zhao, Yuntian Tang

{"title":"Pan-cancer landscape of basement membrane: multi-omics research and single-cell sequencing validation.","authors":"Yi Tang, Qiuhuan Zhang, Zhuoer Yuan, De Yin, Shengyue Zhang, Yucao Sun, Chong-de Mo, Zhenyong Tang, Jiehua Zhao, Yuntian Tang","doi":"10.1080/15384101.2025.2539645","DOIUrl":"10.1080/15384101.2025.2539645","url":null,"abstract":"Epithelial carcinoma cells require penetration of the basement membrane (BM) to metastasize. The BM is a thin layer of extracellular matrix beneath epithelial and endothelial tissues. It acts as a structural barrier, preventing cancer cells from invading and undergoing endocytosis and exocytosis. Thus, understanding the relationship between the BM and tumor immunity can lead to new strategies for halting cancer progression and metastasis. Gene expression data of 33 cancers were obtained from the Cancer Genome Atlas database. The study analyzed the correlation between BM regulatory genes, copy number variations, immune-related genes, and tumor immune dysfunction rejection (TIDE). Immunohistochemical methods were used to analyze the expression of regulatory genes. And the BM score was calculated using single-sample gene set enrichment analysis. Single-cell transcriptional sequencing determined the activation status of the BM in the tumor microenvironment. The expression of BM-related genes (BMGs) exhibited significant heterogeneity across different cancer types. Most genes were up-regulated in tumor tissues. Major single nucleotide polymorphisms of BMGs included missense mutations, while major copy number variations were heterozygous deletion and heterozygous amplification. Additionally, the expressions of immune checkpoint molecules CD276, NRP1, and C10orf54 showed positive correlations with BMS. Numerous tumors displayed a significant positive correlation between BMS and TIDE scores. We demonstrate that BM regulatory genes undergo alterations specific to different cancer types, which are associated with the expression of immune checkpoints and immune dysfunction. This indicates that BM remodeling plays an active role in modulating immune resistance, rather than being a passive structural alteration.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"145-166"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834096","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}

引用次数: 0

NEDD4 is a biomarker of a poor prognosis that contributes to the progression and chemoresistance in small cell lung cancer. NEDD4是一个不良预后的生物标志物，有助于小细胞肺癌的进展和化疗耐药。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-05-01 Epub Date: 2025-08-06 DOI: 10.1080/15384101.2025.2539657

Rong Gao, Yuting Bian, Yongguang Wang, Yani Zhang, Qizhi Zhu, Jinfu Nie, Zongtao Hu, Hongzhi Wang, Bo Hong

{"title":"NEDD4 is a biomarker of a poor prognosis that contributes to the progression and chemoresistance in small cell lung cancer.","authors":"Rong Gao, Yuting Bian, Yongguang Wang, Yani Zhang, Qizhi Zhu, Jinfu Nie, Zongtao Hu, Hongzhi Wang, Bo Hong","doi":"10.1080/15384101.2025.2539657","DOIUrl":"10.1080/15384101.2025.2539657","url":null,"abstract":"Small cell lung cancer (SCLC) accounts for approximately 15% of primary lung carcinomas and has the poorest outcome in all subtypes of lung cancer. The major hurdle for SCLC treatment failure is resistance to platinum-based chemotherapy. Therefore, an unmet need is to discover new targets that promote SCLC progression and chemoresistance. Based on the signature of ubiquitination-related genes (URGs), differentially expressed genes between cisplatin-resistant and cisplatin-sensitive SCLC cell lines were identified using the Genomics of Drug Sensitivity in Cancer (GDSC) database. The URGs associated with the prognosis were further screened by Cox and LASSO regression analyses, as well as a Kaplan-Meier survival analysis. The E3 ligase NEDD4 was identified to be associated with cisplatin resistance, poor prognosis and tumor metastasis in SCLC. The functional enrichment analysis indicated that the functions and pathways regulated by NEDD4 were enriched in cell proliferation, cell invasion, as well as ubiquitination and PI3K-AKT pathways in SCLC. The knockdown and overexpression of NEDD4 demonstrated that NEDD4 induced the phosphorylation of AKT in SCLC cells. Cell viability, wound healing and transwell invasion assays demonstrated that NEDD4 promoted the proliferation, chemoresistance and invasion of SCLC cells. These results suggest that NEDD4 is a biomarker of a poor prognosis for SCLC, and that it promotes AKT activation, SCLC progression and chemoresistance.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"204-219"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788349","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}

引用次数: 0

THBS1 knockdown and baicalin induce pyroptosis via the NF-κB-NLRP3-Caspase-1 axis in gastric cancer cells. THBS1下调和黄芩苷通过NF-κB-NLRP3-Caspase-1轴诱导胃癌细胞凋亡。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-05-01 Epub Date: 2025-08-07 DOI: 10.1080/15384101.2025.2539656

Fan Li, Yanqing Qian, Yanqing Mo, Li Feng

{"title":"THBS1 knockdown and baicalin induce pyroptosis via the NF-κB-NLRP3-Caspase-1 axis in gastric cancer cells.","authors":"Fan Li, Yanqing Qian, Yanqing Mo, Li Feng","doi":"10.1080/15384101.2025.2539656","DOIUrl":"10.1080/15384101.2025.2539656","url":null,"abstract":"Globally, gastric cancer (GC) continues to be the primary cause of death due to cancer. This study aimed to investigate the role of THBS1 in GC and assess the potential synergistic effects of Baicalin and THBS1 knockdown on GC cells. Differential expression analysis of GC-related datasets was conducted, and a protein-protein interaction (PPI) network was established. Key targets were screened, and prognostic genes were identified using a Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. Functional assays assessed the effects of THBS1 knockdown and Baicalin treatment on GC cell behavior and pyroptosis. THBS1 was highly expressed in GC cells, and its knockdown reduced cell behavior, inducing G1 arrest and apoptosis. Combined with Baicalin, these effects were enhanced, synergistically inhibiting GC cell behavior. Detection kits showed that knockdown of THBS1 or baicalin treatment increased lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels, while their combination further exacerbated oxidative stress and cell damage. Western blot (WB) analysis revealed that baicalin combined with THBS1 knockdown synergistically promoted pyroptosis by activating the NLRP3 inflammasome and regulating the NF-κB-NLRP3-Caspase-1 axis. In vivo xenograft models demonstrated that THBS1 knockdown or combined treatment with baicalin significantly inhibited GC progression. These results suggest that THBS1 knockdown combined with baicalin can inhibit GC progression by regulating cell behavior, cell cycle, pyroptosis, and the NF-κB-NLRP3-Caspase-1 axis in GC cells. This mechanism is expected to become a new target for GC treatment.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"183-203"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798295","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}

引用次数: 0

Tissue microarray and liquid biopsy approaches identify EphB3, cMet, and miR-3168 as biomarkers of colorectal cancer. 组织芯片和液体活检方法确定EphB3、cMet和miR-3168是结直肠癌的生物标志物。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-05-01 Epub Date: 2025-08-11 DOI: 10.1080/15384101.2025.2539651

Aisha Naeem, Nikita Gupta, Deborah Berry, Anju Datturgi, Krysta Chaldekas, Brent T Harris, Borbala Mifsud, Olga Rodriguez, Christopher Albanese, Chukwuemeka Ihemelandu

{"title":"Tissue microarray and liquid biopsy approaches identify EphB3, cMet, and miR-3168 as biomarkers of colorectal cancer.","authors":"Aisha Naeem, Nikita Gupta, Deborah Berry, Anju Datturgi, Krysta Chaldekas, Brent T Harris, Borbala Mifsud, Olga Rodriguez, Christopher Albanese, Chukwuemeka Ihemelandu","doi":"10.1080/15384101.2025.2539651","DOIUrl":"10.1080/15384101.2025.2539651","url":null,"abstract":"Colorectal cancer (CRC) remains a significant global health concern, and reliable biomarkers are needed to improve early diagnosis, prognostication, and personalized treatment strategies. This study investigated the expression of cell surface proteins and serum exosomal miRNAs in CRC patients. Tissue microarrays (TMAs) constructed from primary and metastatic CRC samples were analyzed for five cell surface proteins: EphB1, EphB3, EphA2, cMet, and EphB4. Immunohistochemistry was performed on the TMAs to validate their expression levels. We found that the distribution of expression for all four receptors, except EphA2, was significantly higher (p < 0.01) in CRC samples compared to non-cancerous tissue. High expression of EphB3 was detected in 37% of patient samples, followed by cMet, which was observed in 35%. Exosomes were isolated from the serum of three CRC patients with tumors exhibiting high expression of LGR5 and/or EphB3, four healthy donors and two CRC cell lines. Serum exosomal miRNA analysis identified miR-3168 as significantly upregulated in CRC patients, showing a 3.8-fold increase compared to healthy controls (p < 0.001) and a 2.6-fold increase in CRC cell lines compared to controls (p = 0.02). Ingenuity Pathway Analysis (IPA) suggested that miR-3168 may regulate cMet, EphB3, and EphB4, along with other CRC-associated molecules and pathways. These findings highlight the potential of EphB3 and cMet as biomarkers in CRC, and miR-3168 as a promising minimally-invasive biomarker for monitoring disease progression and therapeutic response. However, further validation in larger cohorts is needed to establish their clinical utility.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"167-182"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820676","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}

引用次数: 0

Fasting inhibits glycolysis and migration/invasion in gallbladder cancer via PCBP2/ANGPTL4 signaling. 禁食通过PCBP2/ANGPTL4信号抑制胆囊癌的糖酵解和迁移/侵袭。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-05-01 Epub Date: 2025-08-13 DOI: 10.1080/15384101.2025.2540137

Ying Tao, Sheng Shen, Zijun Gong, Rui Zan, Bohao Zheng, Chaolin Ma, Jin'e Wang, Han Liu, Xiaoling Ni, Houbao Liu, Tao Suo

{"title":"Fasting inhibits glycolysis and migration/invasion in gallbladder cancer via PCBP2/ANGPTL4 signaling.","authors":"Ying Tao, Sheng Shen, Zijun Gong, Rui Zan, Bohao Zheng, Chaolin Ma, Jin'e Wang, Han Liu, Xiaoling Ni, Houbao Liu, Tao Suo","doi":"10.1080/15384101.2025.2540137","DOIUrl":"10.1080/15384101.2025.2540137","url":null,"abstract":"Gallbladder cancer (GBC) is a biliary tract cancer with a poor prognosis. Consistent evidence suggests that fasting has extensive antitumor effects in various cancers and influences levels of poly (rC)-binding protein 2 (PCBP2). However, whether fasting and PCBP2 are involved in GBC remains unknown. We assessed the expression of PCBP2 in GBC tumor tissues and cells. Knockdown and overexpression of PCBP2, combined with in vitro and in vivo assays using fasting mimic medium or diets, were conducted to provide functional significance. The effect of PCBP2 on glycolysis was assessed by glucose uptake, lactate production, oxygen consumption rate, and limiting glycolytic-associated enzymes (PDK1, PKM2, and HK-2). We found that fasting could inhibit glycolysis and cell migration/invasion in GBC cells and that fasting mimic diets could significantly inhibit GBC cell proliferation in a mouse xenograft model. PBCP2 was upregulated in GBC tumor tissues and cells. Moreover, PCBP2 is a key downstream target of fasting, and fasting decreases PCBP2 expression in GBC cells. PCBP2 knockdown inhibits GBC cell proliferation, migration/invasion, and glycolysis, whereas PCBP2 overexpression has the opposite effect. Through co-immunoprecipitation, we identified a physical connection between PCBP2 and the angiopoietin-like protein ANGPTL4. PCBP2 can negatively regulate the expression of ANGPTL4. Hence, fasting inhibits cell proliferation, migration/invasion, and glycolysis through PCBP2/ANGPTL4 signaling. We conclude that PCBP2 is a target of fasting and is involved in cell migration/invasion and glycolysis through the negative regulation of ANGPTL4 in GBC. PCBP2 represents a potential therapeutic target for GBC.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"220-235"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834095","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}

引用次数: 0

Uridine-cytidine kinase 2 promotes glycolysis and reprograms glioblastoma stem cell characteristics under hypoxic conditions through the PI3K/Akt/HIF-1α pathway. 尿苷-胞苷激酶2通过PI3K/Akt/HIF-1α途径促进糖酵解并在缺氧条件下重编程胶质母细胞瘤干细胞特征。

IF 3.4 3区生物学

Cell Cycle Pub Date : 2025-03-01 Epub Date: 2025-08-03 DOI: 10.1080/15384101.2025.2539643

Xiaopeng Ding, Jingying Wang, Peng Yu, Jia Yin

{"title":"Uridine-cytidine kinase 2 promotes glycolysis and reprograms glioblastoma stem cell characteristics under hypoxic conditions through the PI3K/Akt/HIF-1α pathway.","authors":"Xiaopeng Ding, Jingying Wang, Peng Yu, Jia Yin","doi":"10.1080/15384101.2025.2539643","DOIUrl":"10.1080/15384101.2025.2539643","url":null,"abstract":"This study aimed to explore key regulatory molecules involved in metabolic alterations clarify the heterogeneity of glioblastoma and develop novel therapeutic strategies. The microarray dataset GSE45117 was retrieved from the Gene Expression Omnibus database to analyze differentially expressed genes (DEGs) glioma stem cell (GSC) populations were enriched via microsphere suspension culture and ALDH+ cell sorting in vitro with the expression of the uridine-cytidine kinase 2 (UCK2) gene compared between stemness and non-stemness populations the UCK2 gene was stably knocked down or overexpressed in GSCs to assess cell invasion migration glucose uptake lactate production and ATP levels. Database analysis revealed high UCK2 expression in cancer stem cells (CSCs) manipulating UCK2 levels affected stemness factors and cell behaviors including proliferation migration invasion and tumor growth UCK2 was more abundant in hypoxic central tumor regions promoting increased glucose uptake and energy production knocking down UCK2 reduced glycolysis and stem cell properties under hypoxia mechanistically UCK2 stabilizes PI3K protein through deubiquitination thereby activating the Akt/HIF-1α pathway. UCK2 plays a pivotal role as a metabolic regulator in glucose metabolism by stabilizing PI3K protein expression via deubiquitination which in turn activates the Akt/HIF-1α signaling pathway.","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"103-121"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774740","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}

引用次数: 0