Carcinogenesis最新文献_第4页

Correction to: CRL4DCAF4 E3 ligase-mediated degradation of MEN1 transcriptionally reactivates hTERT to sustain immortalization in colorectal cancer cells. 更正为CRL4DCAF4 E3连接酶介导的MEN1转录降解可重新激活hTERT，维持结直肠癌细胞的永生化。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-12 DOI: 10.1093/carcin/bgae039

引用次数: 0

TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway. TMEM16A 可抑制自噬，并通过 mTOR 通路促进下咽鳞状细胞癌的侵袭。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-12 DOI: 10.1093/carcin/bgae020

Xin Yang, Limei Cui, Zhonglu Liu, Yumei Li, Xinxin Wu, Ruxian Tian, Chuanliang Jia, Chao Ren, Yakui Mou, Xicheng Song

{"title":"TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway.","authors":"Xin Yang, Limei Cui, Zhonglu Liu, Yumei Li, Xinxin Wu, Ruxian Tian, Chuanliang Jia, Chao Ren, Yakui Mou, Xicheng Song","doi":"10.1093/carcin/bgae020","DOIUrl":"10.1093/carcin/bgae020","url":null,"abstract":"Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared with normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Capsaicin enhances cisplatin-induced anti-metastasis of nasopharyngeal carcinoma by inhibiting EMT and ERK signaling via serpin family B member 2. 辣椒素通过SERPINB2抑制EMT和ERK信号转导，增强顺铂诱导的鼻咽癌抗转移能力

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-12 DOI: 10.1093/carcin/bgae032

Yafei Xu, Weimiao Kong, Simin Zhao, Dan Xiong, Yejun Wang

{"title":"Capsaicin enhances cisplatin-induced anti-metastasis of nasopharyngeal carcinoma by inhibiting EMT and ERK signaling via serpin family B member 2.","authors":"Yafei Xu, Weimiao Kong, Simin Zhao, Dan Xiong, Yejun Wang","doi":"10.1093/carcin/bgae032","DOIUrl":"10.1093/carcin/bgae032","url":null,"abstract":"Cisplatin (DDP)-based combined chemotherapy or concurrent chemoradiotherapy is the mainstay treatment for advanced-stage nasopharyngeal carcinoma (NPC), but needs improvement due to its severe side effects. Capsaicin (CAP) can enhance the anti-tumor activity of cytotoxic drugs. The aim of this study was to investigate the anti-metastasis activity of CAP in combination with DDP in NPC. Herein, CAP and DDP showed synergistic cytotoxic effects on NPC cells. CAP alone and DDP alone inhibited NPC migration and invasion in vitro and in vivo, and the combination of CAP and DDP had the greatest effect. Moreover, CAP upregulated the mRNA and protein expressions of serpin family B member 2 (SERPINB2). Further results showed that both SERPINB2 mRNA and protein expressions were downregulated in NPC cell lines and tissues and SERPINB2 overexpression inhibited NPC migration and invasion in vitro and in vivo, while silencing SERPINB2 acted oppositely. In addition, SERPINB2 was abnormally expressed in head and neck squamous cell carcinoma and other multiple cancers, and downregulation of SERPINB2 predicted poor prognosis in head and neck squamous cell carcinoma according to the Cancer Genome Atlas database. We further found that SERPINB2 overexpression inhibited epithelial-mesenchymal transition (EMT) and the phosphorylated extracellular signal-regulated kinase (p-ERK), and the inhibitory effect was enhanced by CAP and DDP. Altogether, our results suggest that the combined inhibition of CAP and DDP on NPC metastasis may be related to the inhibition of epithelial-mesenchymal transition and ERK signals mediated by SERPINB2, and CAP may help to improve the efficacy of DDP in the treatment of NPC and develop new therapeutic approaches.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating NF-κB signaling pathway via interaction with TBK1. 高尔基体转运 1B 通过与 TBK1 相互作用激活 NF-κB 信号通路，从而促进宫颈癌的进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-08 DOI: 10.1093/carcin/bgae054

Yixuan Sun, Qihua Peng, Ruiwen Wang, Yifan Yin, Musitaba Mutailifu, Lipeng Hu, Yincheng Teng, Yang Zhou

{"title":"Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating NF-κB signaling pathway via interaction with TBK1.","authors":"Yixuan Sun, Qihua Peng, Ruiwen Wang, Yifan Yin, Musitaba Mutailifu, Lipeng Hu, Yincheng Teng, Yang Zhou","doi":"10.1093/carcin/bgae054","DOIUrl":"https://doi.org/10.1093/carcin/bgae054","url":null,"abstract":"As a preventable disease, cervical cancer (cervical squamous cell carcinoma and endocervical adenocarcinoma - CESC) remains a tumor with high morbidity and mortality worldwide, underscoring the pressing need for effective treatment strategies. This research identified Golgi transport 1B (GOLT1B) as a critical gene involved in the development of cervical cancer. Gene Expression Omnibus (GEO) datasets were investigated to determine the upregulation of GOLT1B in cervical cancer tissue compared to normal tissue. Besides, GOLT1B was found to predict poor prognosis in cervical cancer by utilizing Gene Expression Profiling Interactive Analysis (GEPIA). The functional assay indicated that GOLT1B promoted CESC viability and migration in vitro and in vivo. RNA sequencing results suggested that GOLT1B likely influenced NF-κB pathway. The subsequent western blot and dual luciferase reporter assay revealed the interaction between GOLT1B and TBK1, modulating the NF-κB pathway. More importantly, GOLT1B was also found to regulate immune cells infiltration, suggesting its potential role in tumor microenvironment. In conclusion, GOLT1B promotes CESC progression via interaction with TBK1 and augmentation of NF-κB signaling-mediated cancer-associated inflammation, which provides us a new approach to CESC target therapy.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EIF2S2 transcriptionally upregulates HIF1α to promote gastric cancer progression via activating PI3K/AKT/mTOR pathway. EIF2S2 通过激活 PI3K/AKT/mTOR 通路，转录上调 HIF1α 以促进胃癌进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-07-24 DOI: 10.1093/carcin/bgae043

Zhiyong Wang, Yingyi Zhang, Yingwei Xue, Wei Huang, Hongfeng Zhang

{"title":"EIF2S2 transcriptionally upregulates HIF1α to promote gastric cancer progression via activating PI3K/AKT/mTOR pathway.","authors":"Zhiyong Wang, Yingyi Zhang, Yingwei Xue, Wei Huang, Hongfeng Zhang","doi":"10.1093/carcin/bgae043","DOIUrl":"https://doi.org/10.1093/carcin/bgae043","url":null,"abstract":"Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) is a protein that controls protein synthesis under various stress conditions and is abnormally expressed in several cancers. However, there is limited insight regarding the expression and molecular role of EIF2S2 in gastric cancer. In this study, we identified the overexpression of EIF2S2 in gastric cancer by immunohistochemical (IHC) staining and found a positive correlation between EIF2S2 expression and shorter overall survival and disease-free survival. Functionally, we revealed that EIF2S2 knockdown suppressed gastric cancer cell proliferation and migration, induced cell apoptosis, and caused G2 phase cell arrest. Additionally, EIF2S2 is essential for in vivo tumor formation. Mechanistically, we demonstrated that EIF2S2 transcriptionally regulated hypoxia induicible factor-1 alpha (HIF1α) expression by NRF1. The promoting role of EIF2S2 in malignant behaviors of gastric cancer cells depended on HIF1α expression. Furthermore, the PI3K/AKT/mTOR signaling was activated upon EIF2S2 overexpression in gastric cancer. Collectively, EIF2S2 exacerbates gastric cancer progression via targeting HIF1α, providing a fundamental basis for considering EIF2S2 as a potential therapeutic target for gastric cancer patients.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematic assessment of serum i-tRF-AsnGTT in gastric cancer: a potential clinical biomarker. 胃癌血清 i-tRF-AsnGTT 系统评估：一种潜在的临床生物标记物

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-07-18 DOI: 10.1093/carcin/bgae044

Xiaodan Jiang, Xun Li, Yang Li, Yu Zhang, Xinliang Gu, Wei Zong, Xianjuan Shen, Shaoqing Ju

{"title":"Systematic assessment of serum i-tRF-AsnGTT in gastric cancer: a potential clinical biomarker.","authors":"Xiaodan Jiang, Xun Li, Yang Li, Yu Zhang, Xinliang Gu, Wei Zong, Xianjuan Shen, Shaoqing Ju","doi":"10.1093/carcin/bgae044","DOIUrl":"https://doi.org/10.1093/carcin/bgae044","url":null,"abstract":"Since gastric cancer shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence PCR. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ² test, and ROC was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation, infiltration depth of tumors, TNM stage, lymph node metastases, and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The interplay of DNA damage and repair, gene expression, and mutagenesis in mammalian cells during oxidative stress. 氧化应激过程中哺乳动物细胞中 DNA 损伤与修复、基因表达和诱变的相互作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-07-18 DOI: 10.1093/carcin/bgae046

Ahmad Besaratinia, Andrew W Caliri, Stella Tommasi

{"title":"The interplay of DNA damage and repair, gene expression, and mutagenesis in mammalian cells during oxidative stress.","authors":"Ahmad Besaratinia, Andrew W Caliri, Stella Tommasi","doi":"10.1093/carcin/bgae046","DOIUrl":"https://doi.org/10.1093/carcin/bgae046","url":null,"abstract":"We investigated the interplay among oxidative DNA damage and repair, expression of genes encoding major base excision repair (BER) enzymes and bypass DNA polymerases, and mutagenesis in mammalian cells. Primary mouse embryonic fibroblasts were challenged with oxidative stress induced by methylene blue plus visible light, and formation and repair of DNA damage, changes in gene expression, and mutagenesis were determined at increasing intervals post-treatment (0 - 192 hours). Significant formation of oxidative DNA damage together with upregulation of Ogg1, Polβ, and Polκ, and no changes in Mutyh and Nudt1 expression were found in treated cells. There was a distinct interconnection between Ogg1 and Polβ expression and DNA damage formation and repair whereby changes in expression of these two genes were proportionate to the levels of oxidative DNA damage, once a 3-plus hour lag time passed (P < 0.05). Equally notable was the matching pattern of Polκ expression and kinetics of oxidative DNA damage and repair (P < 0.05). The DNA damage and gene expression data were remarkably consistent with mutagenicity data in the treated cells; the induced mutation spectrum is indicative of erroneous bypass of oxidized DNA bases and incorporation of oxidized deoxynucleoside triphosphates during replication of the genomic DNA. Our findings support follow-up functional studies to elucidate how oxidation of DNA bases and the nucleotide pool, overexpression of Polκ, delayed upregulation of Ogg1 and Polβ, and inadequate expression of Nudt1 and Mutyh collectively affect mutagenesis consequent to oxidative stress.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Macropinocytosis inhibits alkaliptosis in pancreatic cancer cells through fatty acid uptake. 大吞噬作用通过脂肪酸摄取抑制胰腺癌细胞的碱中毒。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-07-15 DOI: 10.1093/carcin/bgae045

Fangquan Chen, Hu Tang, Junhao Lin, Limin Xiang, Yanjiao Lu, Rui Kang, Daolin Tang, Jiao Liu

{"title":"Macropinocytosis inhibits alkaliptosis in pancreatic cancer cells through fatty acid uptake.","authors":"Fangquan Chen, Hu Tang, Junhao Lin, Limin Xiang, Yanjiao Lu, Rui Kang, Daolin Tang, Jiao Liu","doi":"10.1093/carcin/bgae045","DOIUrl":"https://doi.org/10.1093/carcin/bgae045","url":null,"abstract":"Alkaliptosis, a form of regulated cell death, is characterized by lysosomal dysfunction and intracellular pH alkalinization. The pharmacological induction of alkaliptosis using the small molecule compound JTC801 has emerged as a promising anticancer strategy in various types of cancers, particularly pancreatic ductal adenocarcinoma (PDAC). In this study, we investigate a novel mechanism by which macropinocytosis, an endocytic process involving the uptake of extracellular material, promotes resistance to alkaliptosis in human PDAC cells. Through lipid metabolomics analysis and functional studies, we demonstrate that the inhibition of alkaliptosis by fatty acids, such as oleic acid, is not dependent on endogenous synthetic pathways but rather on exogenous uptake facilitated by macropinocytosis. Consequently, targeting macropinocytosis through pharmacological approaches (e.g., using EIPA or EHoP-016) or genetic interventions (e.g., RAC1 knockdown) effectively enhances JTC801-induced alkaliptosis in human PDAC cells. These findings provide compelling evidence that the modulation of macropinocytosis can increase the sensitivity of cancer cells to alkaliptosis inducers.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy of depatuxizumab mafodotin (ABT-414) in preclinical models of head and neck cancer. 德帕妥珠单抗马福多汀（ABT-414）在头颈癌临床前模型中的疗效。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-07-08 DOI: 10.1093/carcin/bgae014

Lucas Mani, Abdullah Naveed, Ashtyn McAdoo, Eben Rosenthal, Marisa Hom

{"title":"Efficacy of depatuxizumab mafodotin (ABT-414) in preclinical models of head and neck cancer.","authors":"Lucas Mani, Abdullah Naveed, Ashtyn McAdoo, Eben Rosenthal, Marisa Hom","doi":"10.1093/carcin/bgae014","DOIUrl":"10.1093/carcin/bgae014","url":null,"abstract":"Epidermal growth factor receptor (EGFR) is highly expressed in 80-90% of head and neck squamous cell carcinomas (HNSCCs), making it an ideal target for antibody-drug conjugates. Depatuxizumab mafodotin (ABT-414), is an EGFR-targeting ADC comprised of the monoclonal antibody ABT-806 conjugated to monomethyl auristatin F, a tubulin polymerization inhibitor. This study assessed the in vivo efficacy of ABT-414 in HNSCC. The effects of ABT-414 on HNSCCs were determined using in vitro cytotoxicity assays and in vivo flank xenograft mouse models. The distribution of ABT-414 was assessed ex vivo via optical imaging methods using a conjugate of ABT-414 to the near-infrared agent IRDye800. In vitro treatment of high EGFR-expressing human HNSCC cell lines (UMSCC47 and FaDu) with ABT-414 (0-3.38 nM) resulted in dose-dependent cell death (IC50 values of 0.213 nM and 0.167 nM, respectively). ABT-414 treatment of the FaDu mouse xenografts displayed antitumor activity (P = 0.023) without a change in body mass (P = 0.1335), whereas treatment of UMSCC47 did not generate a significant response (P = 0.1761). Fluorescence imaging revealed ABT-414-IRDye800 accumulation in the tumors of both FaDu and UMSCC47 cell lines, with a signal-to-background ratio of >10. ABT-414 treatment yielded antitumor activity in FaDu tumors, but not in UMSCC47, highlighting the potential for ABT-414 efficacy in high EGFR-expressing tumors. Although ABT-414-IRDye800 localized tumors in both cell lines, the differing antitumor responses highlight the need for further investigation into the role of the tumor microenvironment in drug delivery.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long non-coding RNA KB-1460A1.5 promotes ferroptosis by inhibiting mTOR/SREBP-1/SCD1-mediated polyunsaturated fatty acid desaturation in glioma. 长非编码RNA KB-1460A1.5通过抑制胶质瘤中mTOR/SREBP-1/SCD1介导的多不饱和脂肪酸脱饱和来促进铁变态反应。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-07-08 DOI: 10.1093/carcin/bgae016

Lixia Xu, Binli Wen, Qiaoli Wu, Shan Lu, Jianwen Liao, Lidong Mo, Qingguo Li, Xiaoguang Tong, Hua Yan

{"title":"Long non-coding RNA KB-1460A1.5 promotes ferroptosis by inhibiting mTOR/SREBP-1/SCD1-mediated polyunsaturated fatty acid desaturation in glioma.","authors":"Lixia Xu, Binli Wen, Qiaoli Wu, Shan Lu, Jianwen Liao, Lidong Mo, Qingguo Li, Xiaoguang Tong, Hua Yan","doi":"10.1093/carcin/bgae016","DOIUrl":"10.1093/carcin/bgae016","url":null,"abstract":"Ferroptosis is a new form of regulated cell death caused by the iron-dependent peroxidation of phospholipids and is related to cell metabolism, redox homeostasis and various signalling pathways related to cancer. The long non-coding RNA (lncRNA) KB-1460A1.5 acts as a tumour suppressor gene to regulate tumour growth in gliomas, but its molecular network regulatory mechanism is still unclear. In this study, we found that KB-1460A1.5 can induce ferroptosis in glioma and enhance sensitivity to RSL3, a ferroptosis inducer. Tandem mass tag proteomics and nontargeted metabolomics suggest that KB-1460A1.5 affects polyunsaturated fatty acid metabolic processes. Gas chromatography-mass spectrometry-based medium- and long-chain fatty acid-targeted metabolomics confirmed that upregulation of KB-1460A1.5 decreased the levels of monounsaturated fatty acids, oleic acid (OA) and palmitoleic acid (PO) in glioma cells. The addition of OA and PO restored KB-1460A1.5-induced cellular ferroptosis. Molecularly, KB-1460A1.5 inhibited the mammalian target of rapamycin signalling pathway to suppress the expression of downstream sterol regulatory element-binding protein 1 (SREBP-1), thereby attenuating the stearoyl-CoA desaturase-1 (SCD1)-mediated desaturation of polyunsaturated fatty acids. Finally, an animal model of subcutaneous glioma confirmed that KB-1460A1.5 could inhibit tumour progression, SREBP-1/SCD1 expression and ferroptosis. In conclusion, increasing the expression level of KB-1460A1.5 in glioma can promote the induction of oxidative stress and ferroptosis in cancer cells through SREBP-1/SCD1-mediated adipogenesis, demonstrating therapeutic potential in preclinical models.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0