Cell Cycle最新文献

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.

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).

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.

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 KMT2A-rearranged (KMT2Ar) 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 KMT2A status. We found that sensitivity to IMPDHi was independent of KMT2A 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.

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 G₀ 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 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.

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.

Autophagy and cellular senescence are fundamental determinants of tumor cell fate. p16^INK4a 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^INK4a 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^INK4a acted both upstream, modulating autophagic flux, and downstream, as an effector of autophagy-induced senescence. Study heterogeneity limited direct comparisons. Autophagy and p16^INK4a 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.

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.