Cell Cycle最新文献

{"title":"Identification of novel potential homologous repair deficiency-associated genes in pancreatic adenocarcinoma via WGCNA coexpression network analysis and machine learning.","authors":"Chun Liu, Jingyun Fang, Weibiao Kang, Yang Yang, Changjun Yu, Hao Chen, Yongwei Zhang, Huan Ouyang","doi":"10.1080/15384101.2023.2293594","DOIUrl":"10.1080/15384101.2023.2293594","url":null,"abstract":"<p><p>Homologous repair deficiency (HRD) impedes double-strand break repair, which is a common driver of carcinogenesis. Positive HRD status can be used as theranostic markers of response to platinum- and PARP inhibitor-based chemotherapies. Here, we aimed to fully investigate the therapeutic and prognostic potential of HRD in pancreatic adenocarcinoma (PAAD) and identify effective biomarkers related to HRD using comprehensive bioinformatics analysis. The HRD score was defined as the unweighted sum of the LOH, TAI, and LST scores, and it was obtained based on the previous literature. To characterize PAAD immune infiltration subtypes, the \"ConsensusClusterPlus\" package in R was used to conduct unsupervised clustering. A WGCNA was conducted to elucidate the gene coexpression modules and hub genes in the HRD-related gene module of PAAD. The functional enrichment study was performed using Metascape. LASSO analysis was performed using the \"glmnet\" package in R, while the random forest algorithm was realized using the \"randomForest\" package in R. The prognostic variables were evaluated using univariate Cox analysis. The prognostic risk model was built using the LASSO approach. ROC curve and KM survival analyses were performed to assess the prognostic potential of the risk model. The half-maximal inhibitory concentration (IC50) of the PARP inhibitors was estimated using the \"pRRophetic\" package in R and the Genomics of Drug Sensitivity in Cancer database. The \"rms\" package in R was used to create the nomogram. A high HRD score indicated a poor prognosis and an advanced clinical process in PAAD patients. PAAD tumors with high HRD levels revealed significant T helper lymphocyte depletion, upregulated levels of cancer stem cells, and increased sensitivity to rucaparib, Olaparib, and veliparib. Using WGCNA, 11 coexpression modules were obtained. The red module and 122 hub genes were identified as the most correlated with HRD in PAAD. Functional enrichment analysis revealed that the 122 hub genes were mainly concentrated in cell cycle pathways. One novel HRD-related gene signature consisting of CKS1B, HJURP, and TPX2 were screened via LASSO analysis and a random forest algorithm, and they were validated using independent validation sets. No direct association between HRD and <i>CKS1B</i>, <i>HJURP</i>, or <i>TPX2</i> has not been reported in the literature so far. Thus, these findings indicated that <i>CKS1B</i>, <i>HJURP</i>, and <i>TPX2</i> have potential as diagnostic and prognostic biomarkers for PAAD. We constructed a novel HRD-related prognostic model that provides new insights into PAAD prognosis and immunotherapy. Based on bioinformatics analysis, we comprehensively explored the therapeutic and prognostic potential of HRD in PAAD. One novel HRD-related gene signature consisting of CKS1B, HJURP, and TPX2 were identified through the combination of WGCNA, LASSO analysis and a random forest algorithm. A novel HRD-related risk model that can predict clini","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828340","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}

{"title":"<i>SMAD7</i> gene polymorphisms and their influence on patients with colorectal cancer.","authors":"Yongsheng Wu, Jue Xu, Biaobin Tan, Ting Yi, Su Liu, Guang Yang, Kai Li, Xinhan Zhao","doi":"10.1080/15384101.2023.2296210","DOIUrl":"10.1080/15384101.2023.2296210","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent malignant tumor, and its pathogenesis is still not fully understood. Studies have shown that <i>SMAD7</i> gene polymorphisms can affect CRC susceptibility, but the results have been inconsistent and require additional confirmation. Our study aimed to evaluate the effect of <i>SMAD7</i> variants on the risk of CRC in the Chinese Han population. A total of five single nucleotide polymorphisms (SNPs) in <i>SMAD7</i> were genotyped among 696 CRC patients and 696 healthy participants using the MassARRAY iPLEX platform. SNPs were evaluated for their associations with CRC using logistic regression analysis under multiple genetic models. The false-positive report probability (FPRP) analysis was used to validate the positive findings. Our study indicated that rs11874392 showed an increased association with CRC risk (odds ratio, 1.31; 95% confidence interval, 1.04-1.67; <i>p</i> = 0.024). Stratified analysis showed that rs11874392 might increase the risk of CRC in females (OR = 1.70, <i>p</i> = 0.028), individuals with smoking (OR = 1.87, <i>p</i> = 0.026), and drinking (OR = 1.38, <i>p</i> = 0.027). The rs11874392 was found to be related to an elevated risk of rectal cancer (OR = 1.73, <i>p</i> = 0.003), but not with colon cancer. FPRP analysis demonstrated that all of these associations were statistically significant (FPRP <0.2). Additionally, rs11874392 was the strongest predictive model for CRC. This study provides evidence that the <i>SMAD7</i> rs11874392 is related to an increased susceptibility to CRC.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037367","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}

{"title":"SIRT1 alleviates insulin resistance and respiratory distress in late preterm rats by activating QKI5-mediated PPARγ/PI3K/AKT pathway.","authors":"Jinxiao He, Fang Fan, Jingxian Li, Yi Han, Ye Song, Rong Zhang, Yang Xu, Huajie Wu, Rui Fan","doi":"10.1080/15384101.2023.2297567","DOIUrl":"10.1080/15384101.2023.2297567","url":null,"abstract":"<p><p>Neonatal respiratory distress syndrome (NRDS) is a common complication of gestational diabetes mellitus (GDM) and late preterm births. Research suggests that SIRT1 was involved in LPS-induced acute respiratory distress syndrome, but its mechanism remains to be further explored. Here, pregnant rats were intraperitoneally injected with 45 mg/Kg streptozotocin at day 0 of gestation to induce GDM and injected with LPS at day 17 of gestation to induce late preterm birth. Pioglitazone (a PPARγ agonist) was administered from day 17 to parturition in GDM group, and it was administered for 3 days before LPS injection in late preterm birth group. SRT1720 (a SIRT1 activator) was administered by oral gavage from day 0 to day 17 in both groups. Our data showed that activation of SIRT1 or PPARγ alleviated the abnormal blood glucose metabolism and lung tissue injury, downregulated expression of surfactant proteins (SP-B and SP-C), and decreased activation of the PI3K/AKT pathway induced by GDM and late preterm birth in neonatal rats. Moreover, an insulin resistance model was established by treating primary AT-II cells with insulin. Activation of SIRT1 reversed insulin-induced reduction in cell proliferation, glucose consumption, SP-B and SP-C expression, and the activity of the PI3K/AKT pathway and increase in cellular inflammation and apoptosis. Mechanistically, SIRT1 upregulated PPARγ expression via deacetylation of QKI5, an RNA binding protein that can stabilize its target mRNA molecules, and then activated the PI3K/AKT pathway. In conclusion, SIRT1 promotes the expression of PPARγ via upregulation of QKI5 and activates the PI3K/AKT pathway, thus mitigating NRDS caused by GDM and late preterm birth.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037370","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}

{"title":"Transforming growth factor-β and bone morphogenetic protein signaling pathways in pathological cardiac hypertrophy.","authors":"Jing Wen, Guixiang Liu, Mingjie Liu, Huarui Wang, Yunyan Wan, Zhouhong Yao, Nannan Gao, Yuanyuan Sun, Ling Zhu","doi":"10.1080/15384101.2023.2293595","DOIUrl":"10.1080/15384101.2023.2293595","url":null,"abstract":"<p><p>Pathological cardiac hypertrophy (referred to as cardiac hypertrophy) is a maladaptive response of the heart to a variety of pathological stimuli, and cardiac hypertrophy is an independent risk factor for heart failure and sudden death. Currently, the treatments for cardiac hypertrophy are limited to improving symptoms and have little effect. Elucidation of the developmental process of cardiac hypertrophy at the molecular level and the identification of new targets for the treatment of cardiac hypertrophy are crucial. In this review, we summarize the research on multiple active substances related to the pathogenesis of cardiac hypertrophy and the signaling pathways involved and focus on the role of transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling in the development of cardiac hypertrophy and the identification of potential targets for molecular intervention. We aim to identify important signaling molecules with clinical value and hope to help promote the precise treatment of cardiac hypertrophy and thus improve patient outcomes.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097408","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}

{"title":"Exosome-delivered circRNA circSYT15 contributes to cisplatin resistance in cervical cancer cells through the miR-503-5p/RSF1 axis.","authors":"Zhilong Chen, Zhen Xu, Qian Wang, Lu Wang, Hailing Zhang, Wuliang Wang, Hu Zhao, Yilin Guo, Jinquan Cui","doi":"10.1080/15384101.2023.2281768","DOIUrl":"10.1080/15384101.2023.2281768","url":null,"abstract":"<p><p>The development of chemotherapy resistance is a major obstacle for cervical cancer (CC) patients. Exosome-mediated transfer of circular RNAs (circRNAs) was found to have relevance to the CC. This study is designed to explore the role and mechanism of exosomal circRNA synaptotagmin 15 (circSYT15) on cisplatin (DDP) resistance in CC. Cell proliferation ability and apoptosis rate were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), colony formation, and flow cytometry assays. CircSYT15, microRNA-503-5p (miR-503-5p), Remodeling spacing factor 1 (RSF1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Exosomes were analyzed by a transmission electron microscope and nanoparticle tracking analysis. CD63, CD81, TSC101, Bcl-2, Bax, C-caspase 3, and RSF1 protein levels were examined by western blot assay. The binding between miR-503-5p and circSYT15 or RSF1 was predicted by circBank or Starbase and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP). The biological role of exosomal circSYT15 in DDP resistance of CC in vivo. CircSYT15 was upregulated in the DDP-resistant CC cells and exosomes isolated from DDP-resistant CC cells. CircSYT15 knockdown repressed the proliferation and drug resistance of CC and induced apoptosis in CC cells. Exosomes shuttled circSYT15 act as a sponge to affect RSF1 expression, thereby promoting proliferation and drug resistance and repressing apoptosis of sensitive CC cells. Exosomal circSYT15 boost DDP resistance of cervical cancer in vivo. Exosome-mediated transfer of circSYT15 enhanced DDP resistance in CC partly by targeting the miR-503-5p/RSF1 axis, providing a foundation for future clinical applications of CC drug resistance.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396568","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}

{"title":"Role of non-coding RNAs as new therapeutic targets in regulating the EMT and apoptosis in metastatic gastric and colorectal cancers.","authors":"Nasim Ebrahimi, Ali Hakimzadeh, Farima Bozorgmand, Sepehr Speed, Mahdokht Sadat Manavi, Roya Khorram, Kobra Farahani, Fatemeh Rezaei-Tazangi, Atena Mansouri, Michael R Hamblin, Amir Reza Aref","doi":"10.1080/15384101.2023.2286804","DOIUrl":"10.1080/15384101.2023.2286804","url":null,"abstract":"<p><p>Colorectal cancer (CRC) and gastric cancer (GC), are the two most common cancers of the gastrointestinal tract, and are serious health concerns worldwide. The discovery of more effective biomarkers for early diagnosis, and improved patient prognosis is important. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can regulate cellular processes such as apoptosis and the epithelial-mesenchymal transition (EMT) leading to progression and resistance of GC and CRC tumors. Moreover these pathways (apoptosis and EMT) may serve as therapeutic targets, to prevent metastasis, and to overcome drug resistance. A subgroup of ncRNAs is common to both GC and CRC tumors, suggesting that they might be used as biomarkers or therapeutic targets. In this review, we highlight some ncRNAs that can regulate EMT and apoptosis as two opposite mechanisms in cancer progression and metastasis in GC and CRC. A better understanding of the biological role of ncRNAs could open up new avenues for the development of personalized treatment plans for GC and CRC patients.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443989","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}

{"title":"Depleting ANTXR1 suppresses glioma growth via deactivating PI3K/AKT pathway.","authors":"Chaoyang Zhou, Aijun Liang, Jianzhong Zhang, Jingxing Leng, Bin Xi, Bin Zhou, Yu Yang, Ronglan Zhu, Liangchen Zhong, Xingxing Jiang, Dengfeng Wan","doi":"10.1080/15384101.2023.2275900","DOIUrl":"10.1080/15384101.2023.2275900","url":null,"abstract":"<p><p>Gliomas are commonly known as primary brain tumors and associated with frequent recurrence and an unsatisfactory prognosis despite extensive research in the underlying molecular mechanisms. We aimed to examine the role of ANTXR1 in glioma tumorigenesis and explore its downstream regulatory mechanism. ANTXR1 expression in clinical specimens and its relationship with some pathological characteristics were detected using immunohistochemical staining. After silencing/upregulating ANTXR1 through lentiviral transfection in glioma cell lines, qRT-PCR and western blotting were used to examine mRNA and protein levels, and cell phenotype was also detected. ANTXR1-knockdown and -overexpression cells were then processed by AKT activator and PI3K inhibitor, respectively, to verify downstream PI3K/AKT pathway regulated by ANTXR1. Xenograft nude mice models were constructed to verify the role of ANTXR1 <i>in vivo</i>. We found overexpression of ANTXR1 in both cell lines in comparison with those in normal brain tissues. Glioma cell growth and migratory ability were dramatically impaired as a result of silencing <i>ANTXR1</i> by shANTXR1 lentiviruses. ANTXR1 blockade also accelerated cell apoptosis and held back cell cycle via targeting G2 phrase during cell mitosis. <i>In vivo</i> xenograft models verified <i>in vitro</i> findings above. Further exploration disclosed that AKT activator promoted anti-tumor effects mediated by ANTXR1 knockdown, while PI3K inhibitor limited pro-tumor effects mediated by ANTXR1 overexpression, indicating that ANTXR1 functioned in glioma cells through regulating PI3K/AKT pathway. ANTXR1 could play an indispensable role in glioma tumorigenesis via activating PI3K/AKT-mediated cell growth. Our study provides a theoretical basis for targeting ANTXR1 as a molecular target in glioma clinical therapeutics.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396567","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}

{"title":"Investigating the role of LncRNA PSMG3-AS1 in gastric cancer: implications for prognosis and therapeutic intervention.","authors":"Yi Wang, Zhongshi Hong, Shenghong Wei, Zaisheng Ye, Luchuan Chen, Chengzhi Qiu","doi":"10.1080/15384101.2023.2278942","DOIUrl":"10.1080/15384101.2023.2278942","url":null,"abstract":"<p><p>LncRNAs are widely linked to the complex development of gastric cancer, which is acknowledged worldwide as the third highest contributor to cancer-related deaths and the fifth most common form of cancer. The primary focus of this study is to examine the role of LncRNA PSMG3-AS1 in a group of individuals with gastric cancer. The results of our study indicate that PSMG3-AS1 is highly expressed in over 20 different types of cancer. Significantly, there was a clear association found between the expression of PSMG3-AS1 and a multitude of TMB and MSI tumors. PSMG3-AS1 exhibited significant upregulation in gastric cancer patients compared to healthy individuals within the gastric cancer cohort. The prognosis of gastric cancer patients is intrinsically associated with PSMG3-AS1, as confirmed by survival analysis and ROC curves. Furthermore, we created a disruption vector based on LncRNA PSMG3-AS1 and introduced it into AGS and MKN-45 cells, which are human gastric cancer cells. Significant decreases in the expression of the PSMG3-AS1 gene were noticed in both intervention groups compared to the NC group, reflecting the protein level expressions. Significantly, the proliferative and invasive capabilities of MKN-45 and AGS cells were notably reduced following transfection with PSMG3-AS1 siRNA. The results of our study indicate that disruption of the LncRNA PSMG3-AS1 gene may impact the CAV1/miR-451a signaling pathway, thereby leading to a reduction in the ability of gastric cancer cells to multiply and invade.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013626","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}

{"title":"Knockdown of HNRNPM inhibits the progression of glioma through inducing ferroptosis.","authors":"Jian Wang, Xiaolin Luo, Dehua Liu","doi":"10.1080/15384101.2023.2286782","DOIUrl":"10.1080/15384101.2023.2286782","url":null,"abstract":"<p><strong>Purpose: </strong>Ferroptosis acts as an important regulator in diverse human tumors, including the glioma. This study aimed to screen potential ferroptosis-related genes involved in the progression of glioma.</p><p><strong>Materials and methods: </strong>Differently expressed genes (DEGs) were screened based on GSE31262 and GSE12657 datasets, and ferroptosis-related genes were separated. Among the important hub genes in the protein-protein interaction networks, HNRNPM was selected as a research target. Following the knockdown of HNRNPM, the viability, migration, and invasion were detected by CCK8, wound healing, and transwell assays, respectively. The role of HNRNPM knockdown was also verified in a xenograft tumor model in mice. Immunohistochemistry detected the expression levels of HNRNPM and Ki67. Moreover, the ferroptosis was evaluated according to the levels of iron, glutathione peroxidase (GSH), and malondialdehyde (MDA), as well as the expression of PTGS2, GPX4, and FTH1.</p><p><strong>Results: </strong>Total 41 overlapping DEGs relating with ferroptosis and glioma were screened, among which 4 up-regulated hub genes (HNRNPM, HNRNPA3, RUVBL1, and SNRPPF) were determined. The up-regulation of HNRNPM presented a certain predictive value for glioma. In addition, knockdown of HNRNPM inhibited the viability, migration, and invasion of glioma cells in vitro, and also the tumor growth in mice. Notably, knockdown of HNRNPM enhanced the ferroptosis in glioma cells. Furthermore, HNRNPM was positively associated with SMARCA4 in glioma.</p><p><strong>Conclusions: </strong>Knockdown of HNRNPM inhibits the progression of glioma via inducing ferroptosis. HNRNPM is a promising molecular target for the treatment of glioma via inducing ferroptosis. We provided new insights of glioma progression and potential therapeutic guidance.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450988","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}

{"title":"Structural and functional insights into GSDMB isoforms complex roles in pathogenesis.","authors":"Sara Colomo, David Ros-Pardo, Sara S Oltra, Paulino Gomez-Puertas, David Sarrio, Gema Moreno-Bueno","doi":"10.1080/15384101.2023.2287933","DOIUrl":"10.1080/15384101.2023.2287933","url":null,"abstract":"<p><p>SHADSGasdermins (GSDMs) have garnered significant scientific interest due to their protective and detrimental roles in innate immunity, host defense, inflammation, and cancer alongside with other pathologies. While GSDMs are mostly recognized as key effectors of a lytic type of pro-inflammatory cell death known as pyroptosis, they do also take part in other cell death processes (NETosis, secondary necrosis, or apoptosis) and exhibit cell-death independent functions depending on the cellular context. Among GSDMs, Gasdermin B (GSDMB) pyroptotic capacity has been a subject of conflicting findings in scientific literature even when its processing, and subsequent activation, by Granzyme A (GZMA) was decoded. Nevertheless, recent groundbreaking publications have shed light on the crucial role of alternative splicing in determining the pyroptotic capacity of GSDMB isoforms, which depends on the presence of exon 6-derived elements. This comprehensive review pays attention to the relevant structural differences among recently crystalized GSDMB isoforms. As a novelty, the structural aspects governing GSDMB isoform susceptibility to GZMA-mediated activation have been investigated. By elucidating the complex roles of GSDMB isoforms, this review aims to deepen the understanding of this multifunctional player and its potential implications in disease pathogenesis and therapeutic interventions. [Figure: see text].</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458171","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}