Cancer Biology & Therapy最新文献

{"title":"Repression of the SUMO-conjugating enzyme UBC9 is associated with lowered double minutes and reduced tumor progression.","authors":"Yusi Wang, Hongyan Zou, Wei Ji, Min Huang, Benhui You, Nan Sun, Yuandong Qiao, Peng Liu, Lidan Xu, Xuelong Zhang, Mengdi Cai, Ye Kuang, Songbin Fu, Wenjing Sun, Xueyuan Jia, Jie Wu","doi":"10.1080/15384047.2024.2323768","DOIUrl":"10.1080/15384047.2024.2323768","url":null,"abstract":"<p><p>Double minutes (DMs), extrachromosomal gene fragments found within certain tumors, have been noted to carry onco- and drug resistance genes contributing to tumor pathogenesis and progression. After screening for SUMO-related molecule expression within various tumor sample and cell line databases, we found that SUMO-conjugating enzyme UBC9 has been associated with genome instability and tumor cell DM counts, which was confirmed both <i>in vitro</i> and <i>in vivo</i>. Karyotyping determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while RT-qPCR and Western blot were used to measure DM-carried gene expression <i>in vitro</i>. <i>In vivo</i>, fluorescence in situ hybridization (FISH) identified micronucleus (MN) expulsion. Western blot and immunofluorescence staining were then used to determine DNA damage extent, and a reporter plasmid system was constructed to detect changes in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate DM formation and lower DM-carried gene expression, in turn reducing tumor growth and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to increase DNA damage. These findings thus reveal a relationship between heightened UBC9 activity, increased DM counts, and tumor progression, providing a potential approach for targeted therapies, via UBC9 inhibition.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2323768"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells.","authors":"Shufeng Liu, Xiaoguang Chen, Liqi Zhang, Bo Lu","doi":"10.1080/15384047.2024.2329372","DOIUrl":"10.1080/15384047.2024.2329372","url":null,"abstract":"<p><p>Succinylation modification involves in the progression of human cancers. The present study aimed to investigate the role of CPT1A, which is a succinyltransferase in the progression of prostate cancer (PCa). CCK-8 was used to detect the cell viability. Seahorse was performed to evaluate the cell glycolysis. Luciferase assay was used to detect the transcriptional regulation. ChIP was performed to assess the binding between transcriptional factors with the promoters. Co-IP was used to assess the binding between proteins. We found that CPT1A was highly expressed in PCa tissues and cell lines. Silencing of CPT1A inhibited the viability and glycolysis of PCa cells. Mechanistically, CPT1A promoted the succinylation of SP5, which strengthened the binding between SP5 and the promoter of PDPK1. SP5 activated PDPK1 transcription and PDPK1 activated the AKT/mTOR signal pathway. These findings might provide novel targets for the diagnosis or therapy of prostate cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2329372"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2024.2299054","DOIUrl":"10.1080/15384047.2024.2299054","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2299054"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia promotes non-small cell lung cancer cell stemness, migration, and invasion via promoting glycolysis by lactylation of SOX9.","authors":"Fei Yan, Yue Teng, Xiaoyou Li, Yuejiao Zhong, Chunyi Li, Feng Yan, Xia He","doi":"10.1080/15384047.2024.2304161","DOIUrl":"10.1080/15384047.2024.2304161","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the deadliest form of malignancy and the most common subtype is non-small cell lung cancer (NSCLC). Hypoxia is a typical feature of solid tumor microenvironment. In the current study, we clarified the effects of hypoxia on stemness and metastasis and the molecular mechanism.</p><p><strong>Methods: </strong>The biological functions were assessed using the sphere formation assay, Transwell assay, and XF96 extracellular flux analyzer. The protein levels were detected by western blot. The lactylation modification was assessed by western blot and immunoprecipitation. The role of SOX9 in vivo was explored using a xenografted tumor model.</p><p><strong>Results: </strong>We observed that hypoxia promoted sphere formation, migration, invasion, glucose consumption, lactate production, glycolysis, and global lactylation. Inhibition of glycolysis suppressed cell stemness, migration, invasion, and lactylation. Moreover, hypoxia increased the levels of SOX9 and lactylation of SOX9, whereas inhibition of glycolysis reversed the increase. Additionally, knockdown of SOX9 abrogated the promotion of cell stemness, migration, and invasion. In tumor-bearing mice, overexpression of SOX9 promoted tumor growth, and inhibition of glycolysis suppressed tumor growth.</p><p><strong>Conclusion: </strong>Hypoxia induced the lactylation of SOX9 to promote stemness, migration, and invasion via promoting glycolysis. The findings suggested that targeting hypoxia may be an effective way for NSCLC treatment and reveal a new mechanism of hypoxia in NSCLC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2304161"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10793688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>DSN1</i> may predict poor prognosis of lower-grade glioma patients and be a potential target for immunotherapy.","authors":"Yulong Jia, Meiling Liu, Han Liu, Wenjia Liang, Qingyun Zhu, Chao Wang, Yake Chen, Yanzheng Gao, Zhendong Liu, Xingbo Cheng","doi":"10.1080/15384047.2024.2425134","DOIUrl":"10.1080/15384047.2024.2425134","url":null,"abstract":"<p><p>DSN1 has been previously found to be positively correlated with various cancers. However, the effect of DSN1 or its methylation on the prognosis, molecular characteristics, and immune cell infiltration of low-grade glioma (LGG) has not yet been studied. We obtained 1046 LGG samples from the The Cancer Genome Atlas, The Chinese Glioma Genome Atlas (CGGA) microarray, and CGGA RNA-Seq databases. Bioinformatic methods (gene set enrichment analysis (GSEA), chi-square test, multivariate), and laboratory validation were used to investigate DSN1 in LGG. The expression levels of DSN1 mRNA and protein in LGG were substantially higher than those in normal brain tissue, and their expression was negatively regulated by methylation. The survival time of patients with low expression of DSN1 and cg12601032 hypermethylation was considerably prolonged. DSN1 was a risk factor, and of good diagnostic and prognostic value for LGG. Importantly, the expression of DSN1 is related to many types of tumor-infiltrating immune cells and has a positive correlation with PDL1. DSN1 promoted the activation of multiple cancer-related pathways, such as the cell cycle. Additionally, knockdown of DSN1 substantially inhibited the proliferation and invasion of LGG cells. To the best of our knowledge, this study is the first comprehensive analysis of the mechanism of DSN1 leading to poor prognosis of LGG, which provides a new perspective for revealing the pathogenesis of LGG. DSN1 or its methylation has diagnostic value for the prognosis of glioma, and may become a new biological target of anti-tumor immunotherapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2425134"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LCP1 promotes ovarian cancer cell resistance to olaparib by activating the JAK2/STAT3 signalling pathway.","authors":"Minxue Gai, Lanlan Zhao, Hongqi Li, Guoyu Jin, Wei Li, Fei Wang, Ming Liu","doi":"10.1080/15384047.2024.2432117","DOIUrl":"10.1080/15384047.2024.2432117","url":null,"abstract":"<p><strong>Background: </strong>Resistance to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) remain a major challenge in ovarian cancer (OC) treatment. However, the underlying mechanism of PARPi resistance is still poorly characterized. Increasing evidence has proven that lymphocyte cytosolic protein 1 (LCP1) promotes tumor progression. The JAK2/STAT3 signaling pathway plays an important role in increasing tumor metastatic ability and chemoresistance in cancer by promoting epithelial - mesenchymal transition (EMT).</p><p><strong>Methods: </strong>We established an olaparib-resistant OC cell line and studied its toxicologic effects through cell survival, Transwell, colony formation, western blotting and flow cytometry assays. RNA sequencing and screening were then performed to identify genes associated with olaparib resistance. Lymphocyte cytosolic protein 1 (LCP1) was found to be overexpressed in olaparib-resistant OC cells.</p><p><strong>Results: </strong>The inhibition of cell survival and promotion of cell apoptosis induced by olaparib in parental cells were significantly attenuated in olaparib-resistant cells. LCP1 was upregulated in olaparib-resistant cells compared with parental OC cells. Moreover, we found that the protein levels of JAK2/STAT3 signaling pathway components and EMT markers were increased in olaparib-resistant cells. Overexpression of LCP1 increased olaparib resistance in OC cells, and knockdown of LCP1 attenuated olaparib resistance. The changes in the protein levels of JAK2/STAT3 signaling pathway members and EMT markers between the cell types were similar to the changes in the levels of LCP1.</p><p><strong>Conclusions: </strong>These findings indicate that LCP1 expression may play an important role in the resistance of OC to olaparib by activating the JAK2/STAT3 signaling pathway and EMT. LCP1 could be a potential therapeutic target for patients with OC who are resistant to olaparib. Our study provides a new mechanism of olaparib resistance.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2432117"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53AIP1 induce autophagy via the AKT/mTOR signaling pathway in the breast cancer cells.","authors":"Shutian Liu, Ting Xu, Xi Chen, Li Tang, Longjiang Li, Li Zhang, Yongqiang Yang, Jiayi Huang","doi":"10.1080/15384047.2024.2398297","DOIUrl":"10.1080/15384047.2024.2398297","url":null,"abstract":"<p><p>Breast cancer ranks the first in the incidence of female cancer and is the most common cancer threatening the life and health of women worldwide.Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) is a pro-apoptotic gene downstream of p53. However, the role of TP53AIP1 in BC needs to be investigated. In vitro and in vivo experiments were conducted to assess the biological functions and associated mechanisms. Several bioinformatics analyses were made, CCK8 assay, wound healing, transwell assays, colony formation assay, EDU, flow cytometry, Immunofluorescence, qRT-PCR and Western-blotting were performed. In our study, we discovered that BC samples had low levels of TP53AIP1 expression, which correlated with a lower survival rate in BC patients. When TP53AIP1 was up-regulated, it caused a decrease in cell proliferation, migration, and invasion. It also induced epithelial-to-mesenchymal transition (EMT) and protective autophagy. Furthermore, the over-expression of TP53AIP1 suppressed tumor growth when tested in vivo. We also noticed that TP53AIP1 up-regulation resulted in decreased levels of phosphorylation in AKT and mTOR, suggesting a mechanistic role. In addition, we performed functional rescue experiments where the activation of AKT was able to counteract the impact of TP53AIP1 on the survival and autophagy in breast cancer cell lines. This suggests that TP53AIP1 acts as an oncogene by controlling the AKT/mTOR pathway. These findings reveal TP53AIP1 as a gene that suppresses tumor growth and triggers autophagy through the AKT/mTOR pathway in breast cancer cells. As a result, TP53AIP1 presents itself as a potential target for novel therapeutic approaches in treating breast cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2398297"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anticancer mechanisms of <i>Toxoplasma gondii</i> rhoptry protein 16 on lung adenocarcinoma cells.","authors":"Guangqi Li, Qinhui Li, Yongqing Tong, Jin Zeng, Tiantian Dang, Ningai Yang, Yuning Zhou, Lei Ma, Qirui Ge, Zhijun Zhao","doi":"10.1080/15384047.2024.2392902","DOIUrl":"10.1080/15384047.2024.2392902","url":null,"abstract":"<p><p>Lung adenocarcinoma is the most prevalent subtype of lung cancer, which is the leading cause of cancer-related mortality worldwide. <i>Toxoplasma gondii</i> (<i>T.gondii</i>) Rhoptry protein 16 (ROP16) has been shown to quickly enter the nucleus, and through activate host cell signaling pathways by phosphorylation STAT3 and may affect the survival of tumor cells. This study constructed recombinant lentiviral expression vector of <i>T. gondii</i> ROP16 I/II/III and stably transfected them into A549 cells, and the effects of ROP16 on cell proliferation, cell cycle, apoptosis, invasion, and migration of A549 cells were explored by utilizing CCK-8, flow cytometry, qPCR, Western blotting, TUNEL, Transwell assay, and cell scratch assay, and these effects were confirmed in the primary human lung adenocarcinoma cells from postoperative cancer tissues of patients. The type I and III ROP16 activate STAT3 and inhibited A549 cell proliferation, regulated the expression of p21, CDK6, CyclinD1, and induced cell cycle arrest at the G1 phase. ROP16 also regulated the Bax, Bcl-2, p53, cleaved-Caspase3, and Caspase9, inducing cell apoptosis, and reduced the invasion and migration of A549 cells, while type II ROP16 protein had no such effect. Furthermore, in the regulation of ROP16 on primary lung adenocarcinoma cells, type I and III ROP16 showed the same anticancer potential. These findings confirmed the anti-lung adenocarcinoma effect of type I and III ROP16, offering fresh perspectives on the possible application of ROP16 as a target with adjuvant therapy for lung adenocarcinoma and propelling the field of precision therapy research toward parasite treatment of tumors.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2392902"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3.","authors":"Yan Wang, Wen-Xian Guan, Yuan Zhou, Xiao-Yu Zhang, Hai-Jian Zhao","doi":"10.1080/15384047.2023.2284849","DOIUrl":"10.1080/15384047.2023.2284849","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the effect of red ginseng polysaccharide (RGP) on gastric cancer (GC) development and explore its mechanism.</p><p><strong>Methods: </strong>GC cell lines AGS were treated with varying concentrations of RGP (50, 100, and 200 μg/mL). AGS cells treated with 200 μg/mL RGP were transfected with aquaporin 3 (AQP3) overexpression vector. Cell proliferation, viability, and apoptosis were evaluated by MTT, colony formation assay, and flow cytometry, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of AQP3. The levels of Fe2+, malondialdehyde, and lactate dehydrogenase were measured using their respective detection kits, and the reactive oxygen species levels was determined by probe 2',7'-dichlorodihydrofluorescein diacetate. The expression of ferroptosis-related protein and PI3K/Akt pathway-related protein were assessed by western blot. In vivo experiments in nude mice were performed and the mice were divided into four groups (<i>n</i> = 5/group) which gavage administrated with 150 mg/kg normal saline, and 75, 150, 300 mg/kg RGP, respectively. Their tumor weight and volume were recorded.</p><p><strong>Results: </strong>RGP treatment effectively inhibited the proliferation and viability of AGS cells in a dosage-dependent manner and induced apoptosis. It induced ferroptosis in AGS cells, as well as inhibiting the expression of PI3K/Akt-related proteins. AQP3 overexpression could reversed the effect of RGP treatment on ferroptosis. Confirmatory in vivo experiments showed that RGP could reduce the growth of implanted tumor, with increased RGP concentration resulting in greater tumor inhibitory effects.</p><p><strong>Conclusion: </strong>RGP might have therapeutic potential against GC, effectively inhibiting the proliferation and viability of AGS cells.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2284849"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2024.2389605","DOIUrl":"10.1080/15384047.2024.2389605","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2389605"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}