Cimei Zeng, Denggao Huang, Lei Wang, Haimei Liang, Ximiao Ma
{"title":"沉默ZIC5抑制糖酵解并促进肺腺癌细胞的二亢。","authors":"Cimei Zeng, Denggao Huang, Lei Wang, Haimei Liang, Ximiao Ma","doi":"10.1080/15384047.2025.2501780","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore the effects of silencing Zic family member 5 (ZIC5) on glucose metabolism and disulfidptosis in lung adenocarcinoma (LUAD) cells.</p><p><strong>Methods: </strong>Data from The Cancer Genome Atlas (TCGA) was used to analyze ZIC5 expression in LUAD and its association with patient outcomes. ZIC5 was silenced in A549 and H1299 cells using siRNA. The expression of ZIC5 mRNA and protein was assessed by qRT-PCR and Western blot. Cell proliferation was evaluated through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays, while glucose uptake, lactate production, and ATP levels were measured to assess energy metabolism. Seahorse XF analysis was used to evaluate extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Disulfidptosis was assessed through NADP<sup>+</sup>/NADPH ratio, glutathione (GSH) content, GSSG/GSH ratio, and immunofluorescence staining.</p><p><strong>Results: </strong>ZIC5 is highly expressed in LUAD and is associated with poor patient prognosis. Silencing ZIC5 significantly reduced its mRNA and protein levels in A549 and H1299 cells, markedly inhibited cell proliferation, and led to significant decreases in glucose uptake, lactate production, ATP levels, ECAR, and OCR. Additionally, silencing ZIC5 resulted in an increased NADP<sup>+</sup>/NADPH ratio, decreased GSH levels, and a reduced GSSG/GSH ratio, alongside classic disulfidptosis features.</p><p><strong>Conclusion: </strong>ZIC5 plays a crucial role in promoting LUAD cell proliferation and energy metabolism while inhibiting disulfidptosis. Silencing ZIC5 markedly suppresses these processes, indicating its potential as a therapeutic target in LUAD.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2501780"},"PeriodicalIF":4.4000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080275/pdf/","citationCount":"0","resultStr":"{\"title\":\"Silencing ZIC5 suppresses glycolysis and promotes disulfidptosis in lung adenocarcinoma cells.\",\"authors\":\"Cimei Zeng, Denggao Huang, Lei Wang, Haimei Liang, Ximiao Ma\",\"doi\":\"10.1080/15384047.2025.2501780\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>This study aims to explore the effects of silencing Zic family member 5 (ZIC5) on glucose metabolism and disulfidptosis in lung adenocarcinoma (LUAD) cells.</p><p><strong>Methods: </strong>Data from The Cancer Genome Atlas (TCGA) was used to analyze ZIC5 expression in LUAD and its association with patient outcomes. ZIC5 was silenced in A549 and H1299 cells using siRNA. The expression of ZIC5 mRNA and protein was assessed by qRT-PCR and Western blot. Cell proliferation was evaluated through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays, while glucose uptake, lactate production, and ATP levels were measured to assess energy metabolism. Seahorse XF analysis was used to evaluate extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Disulfidptosis was assessed through NADP<sup>+</sup>/NADPH ratio, glutathione (GSH) content, GSSG/GSH ratio, and immunofluorescence staining.</p><p><strong>Results: </strong>ZIC5 is highly expressed in LUAD and is associated with poor patient prognosis. Silencing ZIC5 significantly reduced its mRNA and protein levels in A549 and H1299 cells, markedly inhibited cell proliferation, and led to significant decreases in glucose uptake, lactate production, ATP levels, ECAR, and OCR. Additionally, silencing ZIC5 resulted in an increased NADP<sup>+</sup>/NADPH ratio, decreased GSH levels, and a reduced GSSG/GSH ratio, alongside classic disulfidptosis features.</p><p><strong>Conclusion: </strong>ZIC5 plays a crucial role in promoting LUAD cell proliferation and energy metabolism while inhibiting disulfidptosis. Silencing ZIC5 markedly suppresses these processes, indicating its potential as a therapeutic target in LUAD.</p>\",\"PeriodicalId\":9536,\"journal\":{\"name\":\"Cancer Biology & Therapy\",\"volume\":\"26 1\",\"pages\":\"2501780\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080275/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Biology & Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/15384047.2025.2501780\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15384047.2025.2501780","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/14 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Silencing ZIC5 suppresses glycolysis and promotes disulfidptosis in lung adenocarcinoma cells.
Objective: This study aims to explore the effects of silencing Zic family member 5 (ZIC5) on glucose metabolism and disulfidptosis in lung adenocarcinoma (LUAD) cells.
Methods: Data from The Cancer Genome Atlas (TCGA) was used to analyze ZIC5 expression in LUAD and its association with patient outcomes. ZIC5 was silenced in A549 and H1299 cells using siRNA. The expression of ZIC5 mRNA and protein was assessed by qRT-PCR and Western blot. Cell proliferation was evaluated through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays, while glucose uptake, lactate production, and ATP levels were measured to assess energy metabolism. Seahorse XF analysis was used to evaluate extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Disulfidptosis was assessed through NADP+/NADPH ratio, glutathione (GSH) content, GSSG/GSH ratio, and immunofluorescence staining.
Results: ZIC5 is highly expressed in LUAD and is associated with poor patient prognosis. Silencing ZIC5 significantly reduced its mRNA and protein levels in A549 and H1299 cells, markedly inhibited cell proliferation, and led to significant decreases in glucose uptake, lactate production, ATP levels, ECAR, and OCR. Additionally, silencing ZIC5 resulted in an increased NADP+/NADPH ratio, decreased GSH levels, and a reduced GSSG/GSH ratio, alongside classic disulfidptosis features.
Conclusion: ZIC5 plays a crucial role in promoting LUAD cell proliferation and energy metabolism while inhibiting disulfidptosis. Silencing ZIC5 markedly suppresses these processes, indicating its potential as a therapeutic target in LUAD.
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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