Cell Cycle最新文献

{"title":"The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.","authors":"Nian-Siou Wu, I-Chu Ma, Yi-Fan Lin, Huey-Jiun Ko, Joon-Khim Loh, Yi-Ren Hong","doi":"10.1080/15384101.2023.2289753","DOIUrl":"10.1080/15384101.2023.2289753","url":null,"abstract":"<p><p>Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson's disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"2485-2503"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486760","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":"High-density lipoprotein protects vascular endothelial cells from indoxyl sulfate insults through its antioxidant ability.","authors":"Ching Chen, Chia-Chi Chang, I-Ta Lee, Chun-Yao Huang, Feng-Yen Lin, Shing-Jong Lin, Jaw-Wen Chen, Ting-Ting Chang","doi":"10.1080/15384101.2023.2296184","DOIUrl":"10.1080/15384101.2023.2296184","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) patients have a high risk of cardiovascular disease. Indoxyl sulfate (IS) is a uremic toxin that has been shown to inhibit nitric oxide production and cause cell senescence by inducing oxidative stress. High-density lipoprotein (HDL) has a protective effect on the cardiovascular system; however, its impacts on IS-damaged endothelial cells are still unknown. This study aimed to explore the effects of exogenous supplement of HDL on vascular endothelial cells in a uremia-mimic environment. Tube formation, migration, adhesion, and senescence assays were used to evaluate the cell function of human aortic endothelial cells (HAECs). Reactive oxygen species generation was measured by using Amplex red assay. L-NAME and MCI186 were used as a nitric oxide synthase inhibitor and a free radical scavenger, respectively. HDL exerted anti-inflammatory and antioxidant effects via HIF-1α/HO-1 activation and IL-1β/TNF-α/IL-6 inhibition in IS-stimulated HAECs. HDL improved angiogenesis ability through upregulating Akt/eNOS/VEGF/SDF-1 in IS-stimulated HAECs. HDL decreased endothelial adhesiveness via downregulating VCAM-1 and ICAM-1 in IS-stimulated HAECs. Furthermore, HDL reduced cellular senescence via upregulating SIRT1 and downregulating p53 in IS-stimulated HAECs. Importantly, the above beneficial effects of HDL were mainly due to its antioxidant ability. In conclusion, HDL exerted a comprehensive protective effect on vascular endothelial cells against damage from IS through its antioxidant ability. The results of this study might provide a theoretical basis for potential HDL supplementation in CKD patients with endothelial damage.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"2409-2423"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828339","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":"PSMC2 knockdown exerts an anti-tumor role in nasopharyngeal carcinoma through regulating AKT signaling pathway.","authors":"Jin Su, Shousen Hu, Shiping Ding, Kun Feng","doi":"10.1080/15384101.2023.2293590","DOIUrl":"10.1080/15384101.2023.2293590","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma is a major public health problem in several countries, particularly in Southeast Asia and North Africa. However, the mechanism underlying the malignant biological behaviors of nasopharyngeal carcinoma is not fully clear. Our study intended to investigate the functional importance and molecular mechanism of proteasome 26 S subunit ATPase 2 (PSMC2) in the progression of nasopharyngeal carcinoma. We examined the expression of PSMC2 in both nasopharyngeal carcinoma tissues and normal healthy tissues using immunohistochemistry (IHC). Additionally, we conducted a series of cell experiments to verify the functional roles of PSMC2 and to explore the underlying pathway involved. The results revealed that PSMC2 was significantly upregulated in nasopharyngeal carcinoma tissues compared to normal tissues. Moreover, high PSMC2 was shown to closely correlate with the pathological stage and tumor infiltrate in nasopharyngeal carcinoma patients. Functionally, we observed a suppression of nasopharyngeal carcinoma progression upon knocking down PSMC2. This was evidenced by inhibited cell proliferation and migration <i>in vitro</i>, as well as impaired cell growth <i>in vivo</i>, along with increased apoptosis. Mechanistically, the inhibitory effects of PSMC2 silence on nasopharyngeal carcinoma could be reversed by the addition of AKT activator. Overall, our study sheds light on a novel mechanism underlying the development and progression of nasopharyngeal carcinoma, with PSMC2 exerting a positive regulatory role through the modulation of the AKT signaling pathway. A deeper understanding of PSMC2 may contribute to the development of improved treatment strategies for nasopharyngeal carcinoma.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"2381-2391"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828341","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":"Methylation of lncSHGL promotes adipocyte differentiation by regulating miR-149/Mospd3 axis.","authors":"Xianwei Huang, Xiong Liu, Jiyan Lin","doi":"10.1080/15384101.2023.2287367","DOIUrl":"10.1080/15384101.2023.2287367","url":null,"abstract":"<p><p>Obesity poses significant health risks and can negatively impact an individual's quality of life. The human obesity phenotype results from the differentiation of pre-adipocytes into adipocytes, which leads to hypertrophy and hyperplasia in adipose tissue. The molecular mechanisms by which long non-coding RNAs (lncRNAs) modulate adipocyte differentiation, a process implicated in obesity development, remain poorly characterized. A lncRNA which suppressed the hepatic gluconeogenesis and lipogenesis (lncSHGL) was newly identified. Our research aims to elucidate the functional role and mechanistic underpinnings of suppressor of lncSHGL in adipocyte differentiation. We observed that lncSHGL expression progressively diminished during 3T3-L1 differentiation and was downregulated in the liver and perirenal adipose tissue of ob/ob mice. lncSHGL acts as a molecular sponge for miR-149, with Mospd3 identified as a target of miR-149.Overexpression of lncSHGL and inhibition of miR-149 led to suppressed 3T3-L1 proliferation, decreased lipid droplet accumulation, and attenuated promoter activity of PPARγ2 and C/EBPα. These changes consequently resulted in reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα, as well as inhibited the PI3K/AKT/mTOR signaling pathway. In contrast, lncSHGL suppression yielded opposing outcomes. Moreover, the effects of lncSHGL overexpression and miR-149 inhibition on reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα were reversible upon miR-149 overexpression and Mospd3 suppression. These findings were further validated <i>in vivo</i>. We also discovered a significant increase in methylation levels during 3T3-L1 differentiation, with lncSHGL highly expressed in the presence of a methylation inhibitor. In conclusion. lncSHGL methylation facilitates adipocyte differentiation by modulating the miR-149/Mospd3 axis. Targeting lncSHGL expression may represent a promising therapeutic strategy for obesity-associated adipogenesis, particularly in the context of fatty liver disease.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"2361-2380"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497872","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":"CXADR promote epithelial-mesenchymal transition in endometriosis by modulating AKT/GSK-3β signaling.","authors":"Hang-Jing Tan, Zi-Heng Deng, Chun Zhang, Hong-Wen Deng, Hong-Mei Xiao","doi":"10.1080/15384101.2023.2296242","DOIUrl":"10.1080/15384101.2023.2296242","url":null,"abstract":"<p><p>Endometriosis is a benign high prevalent disease exhibiting malignant features. However, the underlying pathogenesis and key molecules of endometriosis remain unclear. By integrating and analysis of existing expression profile datasets, we identified coxsackie and adenovirus receptor (CXADR), as a novel key gene in endometriosis. Based on the results of immunohistochemistry (IHC), we confirmed significant down-regulation of CXADR in ectopic endometrial tissues obtained from women with endometriosis compared with healthy controls. Further <i>in vitro</i> investigation indicated that CXADR regulated the stability and function of the phosphatases and AKT inhibitors PHLPP2 (pleckstrin homology domain and leucine-rich repeat protein phosphatase 2) and PTEN (phosphatase and tensin homolog). Loss of CXADR led to phosphorylation of AKT and glycogen synthase kinase-3β (GSK-3β), which resulted in stabilization of an epithelial-mesenchymal transition (EMT) factor, SNAIL1 (snail family transcriptional repressor 1). Therefore, EMT processs was induced, and the proliferation, migration and invasion of Ishikawa cells were enhanced. Over-expression of CXADR showed opposite effects. These findings suggest a previously undefined role of AKT/GSK-3β signaling axis in regulating EMT and reveal the involvement of a CXADR-induced EMT, in pathogenic progression of endometriosis.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"2436-2448"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037368","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":" ","pages":"2424-2435"},"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":"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":"&lt;p&gt;&lt;p&gt;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 &lt;i&gt;CKS1B&lt;/i&gt;, &lt;i&gt;HJURP&lt;/i&gt;, or &lt;i&gt;TPX2&lt;/i&gt; has not been reported in the literature so far. Thus, these findings indicated that &lt;i&gt;CKS1B&lt;/i&gt;, &lt;i&gt;HJURP&lt;/i&gt;, and &lt;i&gt;TPX2&lt;/i&gt; 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":" ","pages":"2392-2408"},"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":"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":" ","pages":"2449-2466"},"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":" ","pages":"2467-2484"},"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":"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":" ","pages":"2097-2112"},"PeriodicalIF":3.4,"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}