Cell Cycle [JOURNAL]
Sun
200 papers
Goosecoid facilitates the metastasis of pancreatic adenocarcinoma by enhancing EMT and stemness via regulating TGF-β/SMAD2/3 signaling.
Meng Y, Li R, Jiang W … +5 more , Chen W, Xu Z, Li Z, Hou Y, Wang T
Cell Cycle · 2026 Dec · PMID 41532321 · Full text
Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignant tumor of the gastrointestinal tract. Goosecoid (GSC), translated from a homeobox gene, is a protein participating in metastasis of assorted tumors. This s...
Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignant tumor of the gastrointestinal tract. Goosecoid (GSC), translated from a homeobox gene, is a protein participating in metastasis of assorted tumors. This study explores the role of GSC implicated in tumor metastasis, in PAAD progression. GSC expression in PAAD tissues and cells were tested by quantitative polymerase chain reaction (PCR) and western blot. GSC mRNA and protein expressions were elevated in PAAD tissues and cells. The impacts of GSC depletion or upregulation on PAAD cell proliferation, migration, invasion, cell cycle, and apoptosis were determined by colony formation assay, transwell assay, and flow cytometry. E-cadherin and N-cadherin expressions were tested through immunofluorescence to evaluate the epithelial-mesenchymal transition (EMT) process. The results showed that GSC depletion notably restrained cell proliferative and migratory capabilities and cell cycle, declined MMP2 and MMP9 activity, suppressed EMT process, and enhanced cell apoptosis. Nevertheless, GSC overexpression showed the opposite functions. Stem cell markers CD44 and CD133 were suppressed by GSC depletion and enhanced by GSC overexpression. Additionally, a sphere formation assay was implemented to test cell stemness. The levels of key proteins on TGF-β signaling were tested by western blot. GSC could activate TGF-β signaling in cells by promoting SMAD2/3 phosphorylation. The pathway inhibitor SIS3 notably counteracted the functions on cell malignant phenotypes induced by GSC overexpression. Moreover, xenograft tumor-bearing mouse models were established using male BALB/c nude mice to explore the effects of GSC knockdown on tumor growth and metastasis , and we found that GSC knockdown inhibited PAAD tumor growth and metastasis in xenograft models. GSC is expressed at a high level in PAAD and can facilitate PAAD metastasis by enhancing EMT and stemness via regulating TGF-β/SMAD2/3 signaling.
Locus-specific transcriptional regulation of transposable elements by p53.
Freewoman JM, Rosato AJ, Russell TM … +1 more , Cui F
Cell Cycle · 2026 Dec · PMID 41504242 · Full text
The tumor suppressor p53 protects genomic integrity in part by regulating transposable elements (TEs). Studies of p53-TE interactions rely on synthetic DNA and reporter assays, estimating expression only at the family or...
The tumor suppressor p53 protects genomic integrity in part by regulating transposable elements (TEs). Studies of p53-TE interactions rely on synthetic DNA and reporter assays, estimating expression only at the family or subfamily level and lacking locus-specific resolution. To address this limitation, we developed a computational pipeline for ChIP-seq and RNA-seq analysis that employs advanced algorithms to accurately assign short reads mapping to multiple genomic locations. This approach enables precise quantification of TE transcripts at the locus level. By integrating p53 ChIP peaks with differentially expressed TE transcripts, we performed a global analysis of TE expression upon p53 binding. Applying this framework to lung fibroblast IMR90 and colon cancer HCT116 cells treated with p53 activators, we observed a striking pattern: TEs were predominantly activated in normal IMR90 cells but repressed in HCT116 cancer cells. Further analysis of 24 transcriptomes and 10 cistromes confirmed this trend as a distinguishing hallmark between normal and cancer cells. At the family level, normal cells showed broad TE upregulation, whereas cancer cells exhibited selective repression of Alu and LINE elements. These findings provide the first comprehensive, locus-specific view of TE expression associated with p53 binding, implicating a potential role of chromatin context in TE regulation.
TCAB1: a key promoter of tumor growth through telomere maintenance and senescence evasion.
Lin MY, Jiang D, Tian N … +8 more , Yao X, Pan XH, Ma LH, Gao J, Li ZA, Zhu XQ, Zhao XL, Ruan GP
Cell Cycle · 2026 Dec · PMID 41489261 · Full text
TCAB1 (telomerase Cajal body protein 1), encoded by the WRAP53 gene on chromosome 17p13.1, is a molecular scaffold critical for protein-nucleic acid interactions. In normal cells, TCAB1 plays a pivotal role in localizing...
TCAB1 (telomerase Cajal body protein 1), encoded by the WRAP53 gene on chromosome 17p13.1, is a molecular scaffold critical for protein-nucleic acid interactions. In normal cells, TCAB1 plays a pivotal role in localizing telomerase to Cajal bodies, thereby ensuring proper telomere maintenance and genomic stability. In cancer cells, however, TCAB1 is frequently overexpressed, which supports unchecked proliferation and therapy resistance. Conversely, knockdown of TCAB1 triggers multiple tumor-suppressive mechanisms, including G1 cell cycle arrest - mediated by impaired p21 ubiquitination and subsequent Cyclin E/CDK2 inactivation - as well as telomere shortening and genomic instability due to mitochondrial dysfunction and defective DNA repair. Notably, the induction of cellular senescence emerges as a key anticancer mechanism upon TCAB1 depletion, particularly in early-stage tumors retaining wild-type p53. This review delineates the dual roles of TCAB1, highlighting its function as a context-dependent oncoprotein and the therapeutic potential of targeting it to induce senescence.
Circular RNA circ_0050102 promotes colorectal cancer progression via modulation of the miR-3622a-3p/BIRC5 signaling pathway.
Wang B, Zhang B
Cell Cycle · 2026 Dec · PMID 41481139 · Full text
BACKGROUND: Colorectal cancer (CRC) represents a significant global health burden, requiring a deeper understanding of the molecular mechanisms that drive its progression. Circular RNAs (circRNAs) have appeared as crucia...
BACKGROUND: Colorectal cancer (CRC) represents a significant global health burden, requiring a deeper understanding of the molecular mechanisms that drive its progression. Circular RNAs (circRNAs) have appeared as crucial regulators in cancer, with circ_0050102 as a potential functional molecule in CRC. The present study aimed to determine the diagnostic and functional implications of circ_0050102 in CRC pathogenesis. METHODS: The GSE172229, GSE205094, and GSE134834 datasets were used for the comprehensive analyses of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in CRC tumor samples. Functional experiments, including fluorescence in situ hybridization, knockdown assays, flow cytometric analysis, and luciferase reporter assay, were conducted to investigate the effect of circ_0050102 on CRC cell behavior. CircRNA - miRNA - mRNA interaction analysis provided information about the regulatory network that involved circ_0050102, miR-3622a-3p, and baculoviral IAP repeat-containing 5 (BIRC5). Furthermore, the functional impact of circ_0050102 on CRC tumor growth was investigated using in vivo xenograft models. RESULTS: Our analysis determined circ_0050102 as a significantly differentially expressed circRNA in CRC, with a high area under the receiver operating characteristic curve value, indicating its diagnostic potential. Functional experiments revealed that circ_0050102 is predominantly localized in the cytoplasm of CRC tumor cells, and its knockdown significantly attenuates various CRC cell behavior aspects, including viability, invasion, and migration (p < 0.05). The interaction analysis revealed a potential regulatory axis that involves circ_0050102, miR-3622a-3p, and BIRC5. In vivo experiments demonstrated that circ_0050102 knockdown significantly attenuated CRC tumor development. CONCLUSION: Our results revealed that circ_0050102 promotes CRC progression through miR-3622a-3p and BIRC5. The circ_0050102-mediated regulatory network provides valuable information about the intricate mechanisms contributing to CRC pathogenesis.
Identification of mitochondrial permeability transition-related gene signatures to predict lung adenocarcinoma survival and drug response.
Liu L, Gao M, He W … +4 more , Wang M, Zhou S, Wang X, Shu Y
Cell Cycle · 2026 Dec · PMID 41456273 · Full text
This study investigated mitochondrial permeability transition-driven necrosis-related genes (MPTDNRGs) and its association with lung adenocarcinoma (LUAD). We systematically investigated their genetic variation, expressi...
This study investigated mitochondrial permeability transition-driven necrosis-related genes (MPTDNRGs) and its association with lung adenocarcinoma (LUAD). We systematically investigated their genetic variation, expression patterns, and prognostic value. A risk prediction model for MPTDNRGs was contrasted using Cox regression and least absolute shrinkage and selection operator regression analyses. MPTDNRG scores were used to quantify LUAD subtypes. We evaluated their value in the tumor microenvironment (TME), tumor mutational burden (TMB), prognostic prediction, and drug sensitivity in LUAD. The expression level, copy number variation, methylation, and microRNA (miRNA) status of PSMB7 were analyzed. We also analyzed the expression and knockdown efficiency of PSMB7 in LUAD by immunohistochemical staining, real-time fluorescence quantitative polymerase chain reaction, and western blotting. PSMB7 function in LUAD cells and in vivo was assayed using Cell Counting Kit 8, colony formation, wound healing, Transwell assays, flow cytometry, and mouse models. Seven MPTDNRG features were successfully constructed to predict LUAD prognosis and validated in an external cohort. Patients were categorized into high- and low-risk groups based on risk scores. The high-risk group exhibited shorter survival times, lower TME scores, weaker TME cell infiltration, and higher TMB scores than the low-risk group. Cancer stem cell index, mutation frequency, and drug sensitivity significantly differed between the two groups. MPTDNRG score could independently predict LUAD. PSMB7 was highly expressed in various tumors, and copy number variation, methylation, and miRNA expression significantly differed among different cancers. PSMB7 was highly expressed in LUAD tissues and cell lines. PSMB7 knockdown inhibited cancer cell proliferation, migration, invasion, and epithelial - mesenchymal transition, and promoted apoptosis. PSMB7 exerted tumorigenic effects in mice. In conclusion, we comprehensively demonstrated the characterization of MPTDNRGs in LUAD and constructed a new risk prediction model. Meanwhile, PSMB7 was shown to be a possible new target for LUAD treatment.
Correction.
Cell Cycle · 2026 Dec · PMID 41429583 · Full text
Abstract loading — click title to view on PubMed.
Cell cycle-regulated expression of Fam72a from the |Srgap2-Fam72a| master gene leads to Mis18a downregulation.
Nguyen THA, Kim PS, Kutzner A … +1 more , Heese K
Cell Cycle · 2026 Dec · PMID 41414706 · Full text
The novel |Srgap2-Fam72a| master gene, comprising SLIT-ROBO Rho GTPase-activating protein 2 (Srgap2) and family with sequence similarity 72 member A (Fam72a), has attracted attention for its potential role in regulating...
The novel |Srgap2-Fam72a| master gene, comprising SLIT-ROBO Rho GTPase-activating protein 2 (Srgap2) and family with sequence similarity 72 member A (Fam72a), has attracted attention for its potential role in regulating brain plasticity and supporting advanced cognitive functions in humans. Moreover, recent studies have identified Fam72a as a new cell cycle-regulated gene. In this study, we investigated the activity of the intergenic region (IGR) between the native Srgap2 and Fam72a gene pair and the signaling pathways of Fam72a upon mitogen epidermal growth factor (Egf) stimulation. We found that, under mitogen Egf stimulation, the IGR functions as a divergent promoter, simultaneously driving the transcription of Srgap2 and Fam72a in opposite directions. Furthermore, Fam72a downregulates MIS18 kinetochore protein A (Mis18a), a tightly cell cycle-regulated gene, and interferes with the RAC-alpha serine/threonine-protein kinase (Akt1) signaling pathway by downregulating phosphorylated Akt1 at Serine 473, thereby favoring the more direct mitogen activated protein kinase 1 (Mapk1) route to promote cellular proliferation. These findings provide insight into the role of Fam72a during the cell cycle and suggest that it may contribute to the proliferation of neural stem cells (NSCs).
Targeting IMPDH to inhibit SAMHD1 in -rearranged leukaemia.
Klootsema Y, Tsesmetzis N, Sharma S … +14 more , Hofmann S, Thier J, Dirks C, Hormann FM, Yagüe-Capilla M, Bohlin A, Bengtzen S, Lehmann S, Chabes A, Jädersten M, Lundin V, Rudd SG, Lilienthal I, Herold N
Cell Cycle · 2026 Dec · PMID 41399259 · Full text
Cytarabine (ara-C) and fludarabine (F-ara-A) are key drugs in leukaemia treatment. SAMHD1 is known to confer resistance to ara-C and F-ara-A, and we previously identified ribonucleotide reductase inhibitors as indirect S...
Cytarabine (ara-C) and fludarabine (F-ara-A) are key drugs in leukaemia treatment. SAMHD1 is known to confer resistance to ara-C and F-ara-A, and we previously identified ribonucleotide reductase inhibitors as indirect SAMHD1 inhibitors in a phenotypic screen. The inosine monophosphate dehydrogenase (IMPDH) inhibitor mycophenolic acid (MPA) was also a hit in this screen. IMPDH inhibitors (IMPDHi) have previously shown efficacy against -rearranged (r) acute myeloid leukaemia (AML). We investigated whether IMPDH inhibition could enhance the effect of ara-C and F-ara-A in AML cell lines and primary AML samples, and whether this effect was linked to status. We found that sensitivity to IMPDHi was independent of status. IMPDHi synergized with ara-C and F-ara-A in a SAMHD1-dependent manner in a subset of AML cells, but not in acute lymphoblastic leukaemia cell lines. Mechanistically, IMPDHi depleted allosteric SAMHD1 activators GTP and dGTP, thereby increasing active triphosphate metabolites in SAMHD1-proficient, but not SAMHD1-deficient, cells. Our findings suggest that the addition of IMPDHi to ara-C and F-ara-A may have therapeutic benefits in some AML cases.
Beyond translation: systematic insight of the multifaceted roles of GARS1 in cellular biology and disease.
Coronel Vargas G, Iervasi E, Tkachenko K … +4 more , Bellitto D, Raineri M, Bachetti T, Rosano C
Cell Cycle · 2026 Dec · PMID 41392997 · Full text
Human glycyl-tRNA synthetase (GARS), encoded by the GARS1 gene, is a key protein within the aminoacyl-tRNA synthetases family, responsible for catalyzing the attachment of glycine to its corresponding tRNA during protein...
Human glycyl-tRNA synthetase (GARS), encoded by the GARS1 gene, is a key protein within the aminoacyl-tRNA synthetases family, responsible for catalyzing the attachment of glycine to its corresponding tRNA during protein synthesis. While aminoacyl-tRNA synthetases are primarily known for their role in translation, emerging evidence indicates that they also have non-canonical functions in physiological and pathological processes, including metabolism, angiogenesis, immune responses, and inflammation. This review integrates glycyl-tRNA synthetase evolutionary origins, isoform biology, structure function relationships, immune roles, and cellular stress evidence across bladder, prostate, breast, colorectal, and hepatocellular tumors. Unlike prior papers about GARS, we (i) distinguish cytosolic vs mitochondrial GARS isoforms and their detection pitfalls; (ii) synthesize non-canonical mechanisms (neddylation interfaces, extracellular vesicles-mediated C-ter and N-ter peptides, CDH6-dependent signaling); and (iii) provide a comparative reliability map across cancers, identifying urinary bladder cancer as the most substantiated indication with convergent transcriptomic, proteomic, metabolic, and preliminary translational evidence. Current literature is dominated by correlative and in-vitro studies, and prospective clinical validation is scarce. GARS is a promising but incompletely defined oncologic and immunobiologic node; targeted, standardized, and clinically anchored studies are now feasible and necessary.
Dysregulation of the Cyclin D/E2F activity as a core mechanism driving cancer stem cell plasticity and cell cycle dynamics.
Ahmadi Y, Mohammed T, Abolhasani S … +2 more , Abdullah Hamad S, Faiq T
Cell Cycle · 2026 Dec · PMID 41392602 · Full text
Cancer stem cells (CSCs) represent a highly specialized intratumoral compartment responsible for tumor initiation, metastatic dissemination, therapeutic resistance, and disease recurrence. A central conceptual challenge...
Cancer stem cells (CSCs) represent a highly specialized intratumoral compartment responsible for tumor initiation, metastatic dissemination, therapeutic resistance, and disease recurrence. A central conceptual challenge in CSC biology is their capacity to oscillate between a quiescent G state and a proliferative, stem-like phenotype, reflecting a high degree of phenotypic plasticity. Although dysregulation of the G1/S checkpoint is a hallmark of malignant transformation, its mechanistic contribution to CSC identity and plastic behavior remains poorly defined.This review outlines a conceptual model that integrates aberrant G1/S control with CSC state transitions. We propose that defective checkpoint regulation accelerates CSC proliferation, leading to the progressive intracellular accumulation of Cyclin D, which in turn drives a self-reinforcing, rapid G1 progression through phosphorylation-dependent pathways that operate independently of the slower, transcription-driven Cyclin D-Rb-E2F regulatory axis. With continued cycling, depletion of key E2F-regulated DNA replication factors ensues, eventually forcing CSCs into a quiescent, biosynthetic restoration phase. During this interval, essential genomic replication and cell cycle machinery are replenished until microenvironmental or intracellular cues trigger reentry into the proliferative cycle, giving rise to another burst of accelerated division.Through these cyclical perturbations in the Cyclin D/E2F balance, CSCs undergo temporally governed shifts between quiescent and proliferative states, thereby sustaining plasticity, intratumoral heterogeneity, and treatment-resistant phenotypes. This model also identifies potential therapeutic strategies, such as leveraging stimuli-responsive delivery systems that exploit cyclic CSC vulnerabilities.
Migrasomes: the "functional footprints" left by cell migration.
Liu Y, Chen X, Zhou J … +3 more , Wang Q, Ma Y, Zhao K
Cell Cycle · 2026 Dec · PMID 41369152 · Full text
Migrasomes are membrane-bound vesicles that form on the retraction fibers at the trailing edge of migrating cells and are deposited along the migration path upon the rupture of these fibers. As inherently signal-rich com...
Migrasomes are membrane-bound vesicles that form on the retraction fibers at the trailing edge of migrating cells and are deposited along the migration path upon the rupture of these fibers. As inherently signal-rich complexes enriched with diverse bioactive components, migrasomes not only mediate intercellular communication and microenvironmental regulation but also provide novel mechanisms and potential targets for understanding physiological and pathological processes. Although research on migrasome functions is still in its infancy, accumulating evidence suggests that they not only expand existing biological knowledge systems but also exhibit unique potential in elucidating disease mechanisms, developing diagnostic biomarkers, and exploring therapeutic targets. This review summarizes the discovery, biogenesis, biological functions, and methodological advances in migrasome research, with a particular focus on their emerging roles in disease. Additionally, we discuss prevailing challenges and future directions, concluding with a perspective on the clinical translation of migrasomes in diagnostics and therapeutics.
MicroRNAs in chemotherapy-induced peripheral neuropathy: mechanisms and therapies.
Javankiani S, Dehghani F, Yarahmadi F … +10 more , Jahandideh A, Asadi F, Ghasemi M, Akhondi D, Nasiri Z, Zarrintan V, Moradian M, Mehrvar K, Salmannezhad Khorami F, Behfar Q
Cell Cycle · 2026 Dec · PMID 41362222 · Full text
Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of cancer therapies that profoundly disrupts the quality of life for patients. CIPN is characterized by sensory symptoms such as pain, tin...
Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of cancer therapies that profoundly disrupts the quality of life for patients. CIPN is characterized by sensory symptoms such as pain, tingling, and numbness, typically distributed in a "glove and stocking" pattern. Its underlying mechanisms remain incompletely understood, involving complex processes such as heightened neuronal excitability, alterations in ion channel function, neuroinflammation, and glial cell activation. MicroRNAs (miRNAs), small non-coding RNA molecules, play a pivotal role in regulating these processes by modulating gene expression and cellular functions. Emerging evidence suggests that specific miRNAs, including miR-30b-5p, miR-155, miR-124, and miR-21, are involved in regulating pathways that contribute to CIPN-related pain. These miRNAs influence the function of ion channels, glial cell activation, and neuroinflammation. MiRNAs hold significant promise as biomarkers for the early detection of CIPN. This review comprehensively examines the current understanding of miRNA-mediated mechanisms contributing to CIPN development. Key miRNAs implicated in modulating these pathways are discussed in detail, including their potential as diagnostic biomarkers and therapeutic targets. By integrating molecular insights with translational approaches, this review provides a framework for future research and clinical applications targeting miRNA pathways to mitigate CIPN and improve outcomes for cancer patients undergoing chemotherapy.
The curvature code: BCL-w dimers rewire BAX-BCL-2 control of mitochondrial fate and apoptosis.
Santulli G
Cell Cycle · 2025 · PMID 41324221 · Full text
Abstract loading — click title to view on PubMed.
The interplay between autophagy, p16, and senescence in tumor cells: a systematic review.
Palabiyik AA, Palabiyik E
Cell Cycle · 2026 Dec · PMID 41317088 · Full text
Autophagy and cellular senescence are fundamental determinants of tumor cell fate. p16 has emerged as a key regulator at the intersection of these processes, yet its mechanistic role in the autophagy - senescence axis re...
Autophagy and cellular senescence are fundamental determinants of tumor cell fate. p16 has emerged as a key regulator at the intersection of these processes, yet its mechanistic role in the autophagy - senescence axis remains incompletely defined. Understanding this interaction is essential for identifying novel therapeutic opportunities in oncology. A systematic literature search was conducted across PubMed, Web of Science, and Scopus for studies published between January 2000 and April 2025, yielding 10 eligible studies after the application of predefined criteria. Evidence shows a dual role of autophagy in tumor biology. In some models, autophagy increased p16 and senescence-associated β-gal activity, leading to stable growth arrest. Under stress conditions, however, it supported tumor cell survival despite senescence signals. Mechanistically, p16 acted both upstream, modulating autophagic flux, and downstream, as an effector of autophagy-induced senescence. Study heterogeneity limited direct comparisons. Autophagy and p16 interact bidirectionally to regulate senescence, representing a critical axis that can shift tumor cells between suppression and survival. Future research should prioritize standardized protocols, longitudinal models, and therapeutic evaluations to clarify whether targeting this pathway can be translated into effective cancer interventions.
Functions of exosomal microRNAs from adipose tissue in diabetes mellitus and related cardiovascular pathologies.
Li YZ, Zhang YT, Li XH
Cell Cycle · 2026 Dec · PMID 41249941 · Full text
Adipose tissue is central to energy homeostasis and endocrine function, and its dysregulation is a key driver of metabolic disorders. Exosomes, serving as critical intercellular messengers, mediate systemic metabolic res...
Adipose tissue is central to energy homeostasis and endocrine function, and its dysregulation is a key driver of metabolic disorders. Exosomes, serving as critical intercellular messengers, mediate systemic metabolic responses by delivering bioactive cargo, including nucleic acids, proteins, and lipids. Mounting evidence identifies adipose-derived exosomes as potent mediators of obesity-related inflammation and glucose metabolic dysfunction, thereby contributing to insulin resistance and diabetic complications. This review summarizes the pivotal roles of exosomal microRNAs (miRNAs) and highlights their significant potential as a novel class of small RNA therapeutics. Unlike synthetic delivery systems, exosomal miRNAs constitute an inherent delivery vehicle that synergizes natural targeting efficiency with potent gene regulatory functions. This unique combination enables the precise coordination of complex gene networks involved in metabolic disease, offering a distinct advantage over conventional single-target approaches. Consequently, exosomal miRNAs are positioned as promising candidates for pioneering RNA-based therapies against pervasive conditions such as diabetes and cardiovascular disease.
Exosomes in hepatocellular carcinoma: involvement in reprogramming the tumor microenvironment for immune evasion, metastasis, angiogenesis, and drug resistance.
Ghasemian-Irani M, Babaei S, Kazemi T
Cell Cycle · 2025 · PMID 41204822 · Full text
Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer, and its progression is significantly influenced by the tumor microenvironment (TME). Tumor-derived exosomes (TEXs), an important component of the TME, s...
Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer, and its progression is significantly influenced by the tumor microenvironment (TME). Tumor-derived exosomes (TEXs), an important component of the TME, significantly influence tumor growth by regulating immune responses, facilitating metastasis, and enhancing resistance to therapy. These extracellular vesicles (EVs) transport bioactive substances, such as proteins, lipids, and nucleic acids that promote interaction between cells in the TME. Recent research indicates that HCC-derived exosomes can inhibit immune cell activity, specifically in T cells, thus creating an immunosuppressive TME that facilitates tumor immune escape. They also augment metastatic capability by restructuring the extracellular matrix and promoting angiogenesis. Moreover, HCC-derived exosomes have been associated with developing resistance to drug therapy by transferring molecules such as apoptotic signals and oncogenic microRNAs, circRNAs and lncRNA. Understanding how HCC-derived exosomes affect immune modulation, metastasis, and drug resistance could yield innovative therapeutic targets to enhance therapy outcomes. This review focuses on recent research on the diverse functions of TEXs in HCC progression.
Repurposing the anti-gout drug benzbromarone for the treatment of glioma.
Huo M, Wang Z, Guo W … +4 more , Gong J, Lu H, Liu W, Ding L
Cell Cycle · 2026 Dec · PMID 41201217 · Full text
Glioma has long been a threat to human health and new treatments are required to address this health problem. We here explored the potential use of benzbromarone as a supplement to existing chemotherapy strategies. The e...
Glioma has long been a threat to human health and new treatments are required to address this health problem. We here explored the potential use of benzbromarone as a supplement to existing chemotherapy strategies. The effects of benzbromarone on the proliferation and migration of C6 glioma cells were evaluated by MTT and wound healing assays. The effects of benzbromarone on cell cycle arrest and apoptosis in C6 glioma cells were determined by flow cytometry. The effect of benzbromarone on reactive oxygen species (ROS) production was determined through fluorescence microscopy and flow cytometry. Finally, the effect of benzbromarone on the NF-κB pathway was determined by western blotting and immunofluorescence. Benzbromarone inhibited the growth and migration of C6 glioma cells in a concentration-dependent manner. Benzbromarone also induced cell cycle arrest and apoptosis in C6 glioma cells, in addition to increasing ROS generation. Western blot analysis revealed that benzbromarone activated the NF-κB signaling pathway. Our results suggest that benzbromarone induces cytotoxicity through ROS production. These findings indicate the potential of benzbromarone as a treatment of glioma.
CKS2 promotes the malignant phenotypes of bladder cancer cells via PI3K/AKT signaling pathway activation.
Yang T, Kong SP, Xu QL … +5 more , Zhan CX, Wang XT, Li SB, Wang G, Ma JG
Cell Cycle · 2025 · PMID 41200902 · Full text
Cyclin-dependent kinase subunit 2 (CKS2) has been implicated in various malignancies. This study investigates the mechanism by which CKS2 contributes to bladder cancer (BC) progression. Abnormally expressed genes were id...
Cyclin-dependent kinase subunit 2 (CKS2) has been implicated in various malignancies. This study investigates the mechanism by which CKS2 contributes to bladder cancer (BC) progression. Abnormally expressed genes were identified by differential analysis of tumor and normal tissues using Gene Expression Omnibus datasets. Subsequently, functional assays - including cell proliferation, Transwell migration, colony formation, wound healing, flow cytometry, and enzyme-linked immunosorbent assays - were performed to provide cellular evidence supporting the oncogenic function of CKS2 in BC. The results demonstrated significantly elevated CKS2 expression in BC cells than in normal urothelial cells. CKS2 overexpression promoted cell proliferation, cell migration and invasion. Mechanistically, CKS2 overexpression caused a marked reduction in PTEN protein levels, thereby inhibiting PIP3 degradation and indirectly activating the PI3K/AKT signaling pathway. Furthermore, CKS2 promoted phosphorylation and degradation of p27 Kip1 (Thr187), consequently contributing to cell cycle deregulation and further enhancing PI3K/AKT pathway activity. In contrast, CKS2 knockdown produced the opposite effects. Notably, treatment with the PI3K inhibitor LY294002 effectively reversed CKS2-induced BC cell proliferation and metastasis. In conclusion, CKS2 promoted the malignant phenotypes of BC cells by enhancing PI3K/AKT pathway activity through dual mechanisms involving PTEN downregulation and p27 Kip1-mediated cell cycle dysregulation.
"Leucine zipper proteins as emerging therapeutic regulators: structural dynamics, disease associations, and novel targeting strategies".
Kumari A, Mussarrat A, Chakraborty M … +2 more , Bhattacharjee A, Rajan RK
Cell Cycle · 2025 · PMID 41195551 · Full text
Leucine zipper proteins are transcription factors that regulate gene activity through DNA binding and creating stable pairs. They are located in particular tissues and are involved in significant processes like metabolis...
Leucine zipper proteins are transcription factors that regulate gene activity through DNA binding and creating stable pairs. They are located in particular tissues and are involved in significant processes like metabolism, immunity, and stress response. The C/EBPβ (CCAAT/Enhancer-Binding Proteins), which is predominantly active in the liver and spleen, regulates metabolism and immune activity. The GILZ (glucocorticoid-induced leucine zipper), which is located in the brain, lungs, immune cells, and reproductive system, may protect against inflammation and stress. Hormonal signals or oxidative stress may cause these proteins to be activated and transported to the nucleus to turn off or turn on the genes. The disruption of balance, such as the loss of GILZ, drives inflammation, which may cause diseases. Therapies include small molecules, peptides, or DNA decoy therapy. The selective control of these proteins via biomarker profiling and targeted tissue delivery has potential in mitigating cancer, inflammatory, and metabolic diseases.
Mitophagy suppression via lncRNA H19 silencing: a novel strategy to overcome cisplatin resistance in lung adenocarcinoma.
Liu MZ, Shao XY, Wu SH … +6 more , Ning QQ, Zhang C, Du WW, Sun RR, Sun SY, Zhang YW
Cell Cycle · 2025 · PMID 41194501 · Full text
Cisplatin (DDP) resistance substantially compromises treatment efficacy in lung adenocarcinoma (LUAD). This study investigates the role of mitochondrial long non-coding RNA (lncRNA) H19 in mediating DDP resistance. High-...
Cisplatin (DDP) resistance substantially compromises treatment efficacy in lung adenocarcinoma (LUAD). This study investigates the role of mitochondrial long non-coding RNA (lncRNA) H19 in mediating DDP resistance. High-throughput sequencing and RT-qPCR analyses revealed pronounced H19 upregulation in DDP-resistant A549 (A549/DDP) cells relative to parental A549 cells. Subcellular localization studies indicated that H19 is primarily nuclear in A549 cells but translocates to mitochondria in A549/DDP cells. Functional assays demonstrated that H19 silencing in resistant cells attenuated chemoresistance, suppressed proliferation, migration, invasion, and colony formation in vitro, and delayed tumor growth in vivo. H19 knockdown impaired mitophagy and promoted apoptosis, mirroring autophagy inhibition and restoring DDP sensitivity. In contrast, H19 overexpression in A549 cells did not significantly alter mitophagy or cellular behavior. Furthermore, H19 silencing induced its relocalization from mitochondria back to the nucleus in resistant cells, while overexpression did not affect its nuclear localization. These findings establish that H19 translocation to mitochondria promotes DDP resistance, and its downregulation reverses this process by inhibiting mitophagy and resensitizing cells to DDP. As a nucleus-encoded mitochondria-associated lncRNA (ntmtlncRNA), H19 mediates intercompartmental communication, highlighting its potential as a therapeutic target for overcoming DDP resistance in LUAD.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe