Cell Cycle [JOURNAL]
Sun
200 papers
Transforming growth factor-β and bone morphogenetic protein signaling pathways in pathological cardiac hypertrophy.
Wen J, Liu G, Liu M … +6 more , Wang H, Wan Y, Yao Z, Gao N, Sun Y, Zhu L
Cell Cycle · 2023 Nov · PMID 38179789 · Full text
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 a...
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.
The role of CSTF2 in cancer: from technology to clinical application.
Ding J, Su Y, Liu Y … +6 more , Xu Y, Yang D, Wang X, Hao S, Zhou H, Li H
Cell Cycle · 2023 · PMID 38166492 · Full text
A protein called cleavage-stimulating factor subunit 2 (CSTF2, additionally called CSTF-64) binds RNA and is needed for the cleavage and polyadenylation of mRNA. CSTF2 is an important component subunit of the cleavage st...
A protein called cleavage-stimulating factor subunit 2 (CSTF2, additionally called CSTF-64) binds RNA and is needed for the cleavage and polyadenylation of mRNA. CSTF2 is an important component subunit of the cleavage stimulating factor (CSTF), which is located on the X chromosome and encodes 557 amino acids. There is compelling evidence linking elevated CSTF2 expression to the pathological advancement of cancer and on its impact on the clinical aspects of the disease. The progression of cancers, including hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, and pancreatic cancer, is correlated with the upregulation of CSTF2 expression. This review provides a fresh perspective on the investigation of the associations between CSTF2 and various malignancies and highlights current studies on the regulation of CSTF2. In particular, the mechanism of action and potential clinical applications of CSTF2 in cancer suggest that CSTF2 can serve as a new biomarker and individualized treatment target for a variety of cancer types.
Drug-induced inhibition of HMGA and EZH2 activity as a possible therapy for anaplastic thyroid carcinoma.
De Martino M, Pellecchia S, Decaussin-Petrucci M … +6 more , Testa D, Meireles Da Costa N, Pallante P, Chieffi P, Fusco A, Esposito F
Cell Cycle · 2023 · PMID 38165007 · Full text
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal neoplasms in humans, and just limited progresses have been made to extend patient survival and decrease ATC-associated mortality. Thus, the iden...
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal neoplasms in humans, and just limited progresses have been made to extend patient survival and decrease ATC-associated mortality. Thus, the identification of novel therapeutic strategies for treating ATC is needed. Recently, our group has identified two proteins with oncogenic activity, namely HMGA1 and EZH2, with pivotal roles in ATC cancer progression. Therefore, we tested the ability of trabectedin, a HMGA1-targeting drug, and GSK126, an inhibitor of EZH2 enzymatic activity, to impair cell viability of four ATC-derived cell lines. In the present study, we first confirmed the overexpression of and in all ATC-derived cell lines and tissues compared to the normal primary thyroid cells and tissues. Then, treatment of the ATC cell lines with trabectedin and GSK126 resulted in a drastic induction of apoptotic cell death, which increased when the ATC cell lines were treated with a combination of both drugs. Conversely, normal primary human thyroid cells did not show any significant reduction in their viability when exposed to the same drugs. Noteworthy, both drugs induced the deregulation of - and -controlled genes. Altogether, these findings propose the combination of trabectedin and GSK126 as possible novel strategy for ATC therapy.
Identification of molecular subtypes and prognostic model to reveal immune infiltration and predict prognosis based on immunogenic cell death-related genes in lung adenocarcinoma.
Dong Y, Yu X, Song H … +9 more , Chen Q, Zheng B, Ji X, Xu M, Liu J, Sun X, Wang Q, Ren R, Lu H
Cell Cycle · 2023 · PMID 38164943 · Full text
Immunogenic cell death (ICD) has been increasingly indicated to be related to caners. However, ICD's role in Lung adenocarcinoma (LUAD) is still not well investigated. Clinical data along with associated mRNA expression...
Immunogenic cell death (ICD) has been increasingly indicated to be related to caners. However, ICD's role in Lung adenocarcinoma (LUAD) is still not well investigated. Clinical data along with associated mRNA expression profiles from LUAD cases were collected in TCGA and GEO databases. 13 ICD-related genes were identified. Relations of ICD-related genes expression with prognosis of patients, tumor immune microenvironment (TIME) was analyzed. Then, candidate genes were identified and the prognostic signature were constructed. Afterwards, one nomogram incorporating those chosen clinical data together with risk scores were built. Finally, the effect of HSP90AA1, one gene of the prognostic signature, on LUAD cell were analyzed. Two clusters were identified, which were designated as the ICD-high or -low subtype according to ICD-related genes levels. ICD-high subgroup showed good prognosis, high immune cell infiltration degrees, and enhanced immune response signaling activity compared with ICD-low subtype. Moreover, we established and verified the risk signature based on ICD-related genes. High risk group predicted poor prognosis of LUAD independently and presented negative association with immune score and immune status. Furthermore, nomogram contributed to the accurate prediction of LUAD prognostic outcome. Finally, HSP90AA1 levels were remarkably elevated within tumor cells in comparison with healthy pulmonary epithelial cells. HSP90α, HSP90AA1 protein product, promoted growth, migration, and invasion of LUAD cells. Molecular subtypes and prognostic model were identified by incorporating ICD-related genes, and it was related to TIME and might be adopted for the accurate prediction of LUAD prognosis.
LncRNA ABHD11-AS1 activates EGFR signaling to promote cervical cancer progression by preventing FUS-mediated degradation of ABHD11 mRNA.
Yang T, Tian S, Zhao J … +3 more , Pei M, Zhao M, Yang X
Cell Cycle · 2023 · PMID 38146687 · Full text
Cervical cancer is one of the most common gynecological cancers with high metastasis, poor prognosis and conventional chemotherapy. The long non-coding RNA (lncRNA) ABHD11 antisense RNA 1 (ABHD11-AS1) plays a vital role...
Cervical cancer is one of the most common gynecological cancers with high metastasis, poor prognosis and conventional chemotherapy. The long non-coding RNA (lncRNA) ABHD11 antisense RNA 1 (ABHD11-AS1) plays a vital role in tumorigenesis and is involved in cell proliferation, differentiation, and apoptosis. Especially for cervical cancer, the functions and mechanisms of ABHD11-AS1 are still undetermined. In this study, we explored the role and underlying mechanism of ABHD11-AS1 in cervical cancer. We found that ABHD11-AS1 is highly expressed in cervical cancer tissue. The roles of ABHD11-AS1 and EGFR have investigated the loss of function analysis and cell movability in SiHa and Hela cells. Knockdown of ABHD11-AS1 and EGFR significantly inhibited the proliferation, migration, and invasion and promoted apoptosis of SiHa and Hela cells by up-regulating p21 and Bax and down-regulating cyclin D1, Bcl2, MMP9, and Vimentin. ABHD11-AS1 knockdown could decrease the expression of EGFR. In addition, ABHD11-AS1 could regulate the EGFR signaling pathway, including p-EGFR, p-AKT, and p-ERK. Spearman's correlation analysis and cell experiments demonstrated that ABHD11 was highly expressed in tumor tissue and partially offset the effect of shABHD11-AS1 on the proliferation, migration, and invasion of SiHa and Hela cells. Then, RNA pulldown was used to ascertain the mechanisms of ABHD11-AS1 and FUS. ABHD11-AS1 inhibited ABHD11 mRNA degradation by bounding to FUS. A subcutaneous xenograft of SiHa cells was established to investigate the effect of ABHD11-AS1 in tumor tissue. Knockdown of ABDH11-AS1 inhibited tumor growth and decreased the tumor volume. ABHD11-AS1 knockdown inhibited the expression of Ki67 and Vimentin and up-regulated the expression of Tunel. Our data indicated that ABHD11-AS1 promoted cervical cancer progression by activating EGFR signaling, preventing FUS-mediated degradation of ABHD11 mRNA. Our findings provide novel insights into the potential role of lncRNA in cervical cancer therapy.
SIRT1 alleviates insulin resistance and respiratory distress in late preterm rats by activating QKI5-mediated PPARγ/PI3K/AKT pathway.
He J, Fan F, Li J … +6 more , Han Y, Song Y, Zhang R, Xu Y, Wu H, Fan R
Cell Cycle · 2023 Nov · PMID 38146686 · Full text
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 s...
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.
CXADR promote epithelial-mesenchymal transition in endometriosis by modulating AKT/GSK-3β signaling.
Tan HJ, Deng ZH, Zhang C … +2 more , Deng HW, Xiao HM
Cell Cycle · 2023 Nov · PMID 38146657 · Full text
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 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 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.
gene polymorphisms and their influence on patients with colorectal cancer.
Wu Y, Xu J, Tan B … +5 more , Yi T, Liu S, Yang G, Li K, Zhao X
Cell Cycle · 2023 Nov · PMID 38146644 · Full text
Colorectal cancer (CRC) is a prevalent malignant tumor, and its pathogenesis is still not fully understood. Studies have shown that gene polymorphisms can affect CRC susceptibility, but the results have been inconsisten...
Colorectal cancer (CRC) is a prevalent malignant tumor, and its pathogenesis is still not fully understood. Studies have shown that gene polymorphisms can affect CRC susceptibility, but the results have been inconsistent and require additional confirmation. Our study aimed to evaluate the effect of variants on the risk of CRC in the Chinese Han population. A total of five single nucleotide polymorphisms (SNPs) in 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; = 0.024). Stratified analysis showed that rs11874392 might increase the risk of CRC in females (OR = 1.70, = 0.028), individuals with smoking (OR = 1.87, = 0.026), and drinking (OR = 1.38, = 0.027). The rs11874392 was found to be related to an elevated risk of rectal cancer (OR = 1.73, = 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 rs11874392 is related to an increased susceptibility to CRC.
High-density lipoprotein protects vascular endothelial cells from indoxyl sulfate insults through its antioxidant ability.
Chen C, Chang CC, Lee IT … +5 more , Huang CY, Lin FY, Lin SJ, Chen JW, Chang TT
Cell Cycle · 2023 Nov · PMID 38129288 · Full text
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 oxidat...
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.
Identification of novel potential homologous repair deficiency-associated genes in pancreatic adenocarcinoma via WGCNA coexpression network analysis and machine learning.
Liu C, Fang J, Kang W … +5 more , Yang Y, Yu C, Chen H, Zhang Y, Ouyang H
Cell Cycle · 2023 Nov · PMID 38124367 · Full text
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...
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 , , or has not been reported in the literature so far. Thus, these findings indicated that , , and 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 clinical prognosis and immunotherapeutic response in PAAD patients was constructed.
PSMC2 knockdown exerts an anti-tumor role in nasopharyngeal carcinoma through regulating AKT signaling pathway.
Su J, Hu S, Ding S … +1 more , Feng K
Cell Cycle · 2023 Nov · PMID 38123344 · Full text
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 carc...
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 , as well as impaired cell growth , 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.
Methylation of lncSHGL promotes adipocyte differentiation by regulating miR-149/Mospd3 axis.
Huang X, Liu X, Lin J
Cell Cycle · 2023 Nov · PMID 38057958 · Full text
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...
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 . 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.
The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.
Wu NS, Ma IC, Lin YF … +3 more , Ko HJ, Loh JK, Hong YR
Cell Cycle · 2023 Nov · PMID 38053243 · Full text
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 ad...
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.
Structural and functional insights into GSDMB isoforms complex roles in pathogenesis.
Colomo S, Ros-Pardo D, Oltra SS … +3 more , Gomez-Puertas P, Sarrio D, Moreno-Bueno G
Cell Cycle · 2023 Oct · PMID 38037340 · Full text
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...
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].
Understanding cellular senescence: pathways involved, therapeutics and longevity aiding.
Kumar A, Thirumurugan K
Cell Cycle · 2023 Oct · PMID 38031713 · Full text
A normal somatic cell undergoes cycles of finite cellular divisions. The presence of surveillance checkpoints arrests cell division in response to stress inducers: oxidative stress from excess free radicals, oncogene-ind...
A normal somatic cell undergoes cycles of finite cellular divisions. The presence of surveillance checkpoints arrests cell division in response to stress inducers: oxidative stress from excess free radicals, oncogene-induced abnormalities, genotoxic stress, and telomere attrition. When facing such stress when undergoing these damages, there is a brief pause in the cell cycle to enable repair mechanisms. Also, the nature of stress determines whether the cell goes for repair or permanent arrest. As the cells experience transient or permanent stress, they subsequently choose the quiescence or senescence stage, respectively. Quiescence is an essential stage that allows the arrested/damaged cells to go through appropriate repair mechanisms and then revert to the mainstream cell cycle. However, senescent cells are irreversible and accumulate with age, resulting in inflammation and various age-related disorders. In this review, we focus on senescence-associated pathways and therapeutics understanding cellular senescence as a cascade that leads to aging, while discussing the recent details on the molecular pathways involved in regulating senescence and the benefits of therapeutic strategies against accumulated senescent cells and their secretions.
Knockdown of HNRNPM inhibits the progression of glioma through inducing ferroptosis.
Wang J, Luo X, Liu D
Cell Cycle · 2023 Oct · PMID 38016815 · Full text
PURPOSE: 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. MATERIALS AND METHO...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Association of LOX gene G473A polymorphism with the occurrence of allergic rhinitis and efficacy of montelukast sodium in children.
Yao X, Liu Y, Jiao H … +2 more , Ma W, Chen M
Cell Cycle · 2023 Oct · PMID 38009683 · Full text
Allergic rhinitis (AR) is very common in adolescents, and current treatment options are complex and unsatisfactory. The objective of this study was to analyze the association of lysyl oxidase (LOX) gene G473A polymorphis...
Allergic rhinitis (AR) is very common in adolescents, and current treatment options are complex and unsatisfactory. The objective of this study was to analyze the association of lysyl oxidase (LOX) gene G473A polymorphism with susceptibility to AR in children. In addition, we analyzed the therapeutic effect of montelukast sodium on AR. Forty-five children with AR (research group, 8.16±2.88 years old) and 51 healthy children (control group, 8.22±3.87 years old) during the same period were selected. The LOX gene G473A polymorphism was detected with polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The effect of G473A polymorphism in the occurrence of AR was assessed by logistic regression analysis. In addition, the levels of C-reactive protein (CRP), Interleukin (IL-6), and IL-8 were measured to observe the relationship between G473A polymorphism and inflammatory factors. Finally, montelukast sodium was given to children with AR to investigate the effect of G473A polymorphism on clinical outcomes. The number of G473A polymorphisms in the research group was not significantly different from the control group for GA-type ( = 0.521). However, the number of GG-type polymorphisms was less while the number of type AA was more than the control group ( = 0.044 and 0.046). Children carrying the AA gene had an approximately 4-fold increased risk of AR, while those carrying the GG gene had a decreased risk ( < 0.001). Moreover, children carrying the GG gene had lower levels of CRP, IL-6, and IL-8 and better clinical outcomes, while those carrying the AA gene had higher levels of inflammatory factors and worse outcomes (P<0.05). LOX gene G473A polymorphism is closely associated with AR pathogenesis and may have an important research value in antagonizing the therapeutic effect of montelukast sodium.
ACLY promotes gastric tumorigenesis and accelerates peritoneal metastasis of gastric cancer regulated by HIF-1A.
Yan Z, Liu K, Xu P … +11 more , Chen Z, Zhang P, Pei S, Cheng Q, Huang S, Li B, Lv J, Xu Z, Xu H, Yang L, Zhang D
Cell Cycle · 2023 Oct · PMID 38009671 · Full text
Mounting evidence indicates the potential involvement of ATP-citrate lyase (ACLY) in the modulation of various cancer types. Nevertheless, the precise biological significance of ACLY in gastric cancer (GC) remains elusiv...
Mounting evidence indicates the potential involvement of ATP-citrate lyase (ACLY) in the modulation of various cancer types. Nevertheless, the precise biological significance of ACLY in gastric cancer (GC) remains elusive. This study sought to elucidate the biological function of ACLY and uncover its influence on peritoneal metastasis in GC. The expression of ACLY was assessed using both real-time quantitative PCR and western blot techniques. To investigate the impact of ACLY on the proliferation of gastric cancer (GC) cells, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed. The migratory and invasive abilities of GC were evaluated using wound healing and transwell assays. Additionally, a bioinformatics analysis was employed to predict the correlation between ACLY and HIF-1A. This interaction was subsequently confirmed through a chromatin immunoprecipitation (ChIP) assay. ACLY exhibited upregulation in gastric cancer (GC) as well as in peritoneal metastasis. Its overexpression was found to facilitate the proliferation and metastasis of GC cells in both in vitro and in vivo experiments. Moreover, ACLY was observed to play a role in promoting angiogenesis and epithelial-mesenchymal transition (EMT). Notably, under hypoxic conditions, HIF-1A levels were elevated, thereby acting as a transcription factor to upregulate ACLY expression. Under the regulatory influence of HIF-1A, ACLY exerts a significant impact on the progression of gastric cancer, thereby facilitating peritoneal metastasis.
Role of non-coding RNAs as new therapeutic targets in regulating the EMT and apoptosis in metastatic gastric and colorectal cancers.
Ebrahimi N, Hakimzadeh A, Bozorgmand F … +8 more , Speed S, Manavi MS, Khorram R, Farahani K, Rezaei-Tazangi F, Mansouri A, Hamblin MR, Aref AR
Cell Cycle · 2023 Oct · PMID 38009668 · Full text
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, a...
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.
IGF2BP2 promotes glycolysis and hepatocellular carcinoma stemness by stabilizing CDC45 mRNA via m6A modification.
Wu T, Liao L, Wu T … +3 more , Chen S, Yi Q, Xu M
Cell Cycle · 2023 Oct · PMID 37985379 · Full text
A growing number of studies have shown the prognostic importance of Cell division cycle protein 45 (CDC45) in hepatocellular carcinoma (HCC). This study aims to investigate the biological function and mechanism of CDC45...
A growing number of studies have shown the prognostic importance of Cell division cycle protein 45 (CDC45) in hepatocellular carcinoma (HCC). This study aims to investigate the biological function and mechanism of CDC45 in HCC. The differential expression and prognostic significance of CDC45 in HCC and normal tissues were analyzed by bioinformatics. CDC45 was knocked down and the biological effects of CDC45 in HCC and were measured. Subsequently, using RNA m6A colorimetry and Methylated RNA Immunoprecipitation (MeRIP), the levels of m6A modification of total RNA and CDC45 were evaluated in cells. RIP was applied to establish that CDC45 and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) interact. A test using actinomycin D was performed to gauge the stability of the CDC45 mRNA. Furthermore, the regulatory role of IGF2BP2 on CDC45 expression in HCC progression was explored by overexpressing IGF2BP2. High expression of CDC45 was correlated with poor prognosis in HCC patients. Knocking down CDC45 inhibited HCC cell proliferation, migration, invasion, EMT, stemness, and glycolysis, and promoted apoptosis, which was verified through experiments. Additionally, IGF2BP2 was highly expressed in HCC cells, and it was found to interact with CDC45. Knocking down IGF2BP2 resulted in reduced stability of CDC45 mRNA. Moreover, overexpression of IGF2BP2 promoted HCC cell proliferation, migration, invasion, EMT, stemness, and glycolysis, while inhibiting apoptosis, which was reversed by knocking down CDC45. In general, IGF2BP2 promoted HCC glycolysis and stemness by stabilizing CDC45 mRNA via m6A modification. [Figure: see text].
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