Cell Cycle [JOURNAL]
Sun
200 papers
Circular RNA circ_0001829 attenuates G2/M arrest to promote hepatocyte proliferation by sponging miR-3095-3p following liver injury.
Tong H, Wang S, Shi J … +3 more , Pan H, Liu P, Wang L
Cell Cycle · 2026 Dec · PMID 42366556 · Full text
Circular RNAs (circRNAs), a class of non-coding RNAs, are critical regulators of liver injury repair. In this study, using a CCl-induced mouse liver injury model, we conducted high-throughput sequencing to identify circR...
Circular RNAs (circRNAs), a class of non-coding RNAs, are critical regulators of liver injury repair. In this study, using a CCl-induced mouse liver injury model, we conducted high-throughput sequencing to identify circRNAs enriched in the cell cycle pathway. Four circRNAs (circ_0000604, circ_0001350, circ_0001829, and circ_0001830) were significantly upregulated in early liver injury, with dynamic expression patterns closely linked to repair. Of these, circ_0001829 was selected for functional validation. Circ_0001829 overexpression promoted FL83B cell proliferation and alleviated G2/M phase arrest, whereas its knockdown inhibited these effects. This pro-proliferative effect was confirmed in Hepa1-6 cells. Mechanistically, circ_0001829 functions as a molecular sponge for miR-3095-3p, attenuating its repression of the target gene CDC7 and forming a novel competitive endogenous RNA (ceRNA) axis: circ_0001829/miR-3095-3p/CDC7. To the best of our knowledge, this is the first study to demonstrate that circ_0001829 facilitates liver injury repair by promoting cell proliferation and mitigating cell cycle arrest via a ceRNA mechanism. These results offer valuable insights for the development of ncRNA-based therapeutics for liver injury.
Identification of PGF+ endothelial cells associated with plaque instability in carotid atherosclerosis by scRNA-seq and RNA-seq analysis.
Xiang Y, Liu D, Jin W … +7 more , Xu T, Guo L, Wu T, Zheng Y, Xiong X, Xiong H, He H
Cell Cycle · 2026 Dec · PMID 42365589 · Full text
Vascular endothelial dysfunction plays a critical role in the development of atherosclerosis; however, the mechanisms by which endothelial cells contribute to plaque instability remain incompletely understood. In this st...
Vascular endothelial dysfunction plays a critical role in the development of atherosclerosis; however, the mechanisms by which endothelial cells contribute to plaque instability remain incompletely understood. In this study, we performed an integrated analysis of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to characterize endothelial cell heterogeneity associated with carotid plaque instability. Clustering analysis, gene set variation analysis (GSVA), differential gene expression analysis, and KEGG pathway enrichment were conducted to identify key endothelial cell subsets and their functional characteristics. We identified three endothelial cell subsets (subsets 9, 10, and 11) that were significantly enriched in unstable plaques and exhibited upregulation of multiple pro-inflammatory cytokines. Pathway analysis revealed that these subsets were associated with activation of the PI3K - Akt signaling pathway and other inflammation-related pathways. Furthermore, findings were validated in an apolipoprotein E-deficient (ApoE-/-) mouse model, where increased expression of placental growth factor (PGF) and a higher proportion of PGF-positive endothelial cells were observed in atherosclerotic lesions. In conclusion, this study reveals the heterogeneity of endothelial cells in atherosclerotic plaques and identifies pro-inflammatory endothelial subsets potentially associated with plaque instability, providing new insights into the pathogenesis of atherosclerosis.: This study was approved by the Experimental Animal Ethics Committee of Guizhou University of Chinese Medicine (approval number: 2,024,010).
BMSCs-derived exosomal miR-196a-5p promotes macrophage M2 polarization and osteogenesis in postmenopausal osteoporosis through regulating Rspo2/Wnt/β-catenin signaling.
Zhao Y, Liu J, Zhang Y … +3 more , Liang M, Li R, Wang Y
Cell Cycle · 2026 Dec · PMID 42362201 · Full text
This study aimed to investigate the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-EXOs) on postmenopausal osteoporosis (PMOP). Bilateral ovariectomy (OVX) surgery was performed to establish mouse P...
This study aimed to investigate the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-EXOs) on postmenopausal osteoporosis (PMOP). Bilateral ovariectomy (OVX) surgery was performed to establish mouse PMOP models. Histological analysis was conducted using hematoxylin and eosin staining. Gene expression was detected using immunohistochemistry and Western blot. miRNA and mRNA were detected using quantitative reverse transcriptase PCR. Cell functions were analyzed using oil red O, alizarin red, and alkaline phosphatase (ALP) staining, and flow cytometry. The interaction between miR-196a-5p and R-spondin 2 (Rspo2) was verified by luciferase and RNA immunoprecipitation assays. We found that BMSCs-EXOs promoted osteogenesis and macrophage M2 polarization. BMSCs-derived exosomal miR-196a-5p enhanced the effects of BMSCs-EXOs on mediating osteogenesis and M2 polarization. Mechanistically, miR-196a-5p targeted Rspo2, activating Wnt/β-Catenin signaling. BMSCs-derived exosomal miR-196a-5p alleviated the effects of M1 macrophages and promoted the osteogenesis of BMSCs, which was reversed by Rspo2. Furthermore, BMSCs-derived exosomal miR-196a-5p promoted the osteogenesis . However, miR-196a-5p inhibitor exerted the opposite effects, which was reversed by recombinant IL-10. Taken together, BMSCs-derived exosomal miR-196a-5p protects against PMOP by driving macrophage M2 polarization though regulating Rspo2/Wnt/β-Catenin signaling. Therefore, targeting cell-cell communication in the microenvironment of bone lesions may be a promising strategy for PMOP.
MicroRNA-6833-3p drives prostate cancer progression and stemness by targeting the NUMB-mediated NOTCH signaling pathway.
Wang K, Wang G, Shao J … +4 more , Li C, Wang S, Wu H, He H
Cell Cycle · 2026 Dec · PMID 42333722 · Full text
Understanding molecular pathways in prostate cancer (PCa) is essential. This study demonstrates that miR-6833-3p plays a key role in prostate tumorigenesis via multi-omics integration and functional validation. Expressio...
Understanding molecular pathways in prostate cancer (PCa) is essential. This study demonstrates that miR-6833-3p plays a key role in prostate tumorigenesis via multi-omics integration and functional validation. Expression levels of miR-6833-3p, NUMB, and NOTCH1 were measured in PCa cell lines. The direct regulation of NUMB by miR-6833-3p was confirmed via dual-luciferase reporter assays with mutagenesis. Functional effects were examined using NUMB plasmids or miR-6833-3p mimics. Cell function assays and xenograft models in nude mice were employed, with tissues analyzed via HE staining, qRT-PCR, and Western blot. miR-6833-3p and NOTCH1 were upregulated in PCa, while NUMB was downregulated. miR-6833-3p mimics promoted proliferation, migration, and stemness but inhibited apoptosis and the NUMB/NOTCH1 pathway. NUMB overexpression reversed these effects. In vivo, miR-6833-3p accelerated tumor growth and suppressed NUMB/NOTCH1. miR-6833-3p promotes PCa progression and stemness by inhibiting the NUMB-NOTCH pathway, highlighting its potential as a biomarker for detection and targeted therapy.
OTUD5 promotes AML progression by stabilizing SLC7A11 to suppress ferroptosis.
Chen X, Zhao B, Yang W … +5 more , Sun Z, Hu M, Xu P, Guo J, Jiang T
Cell Cycle · 2026 Dec · PMID 42333513 · Full text
Acute myeloid leukemia (AML) is a highly aggressive malignancy with frequent therapeutic resistance, necessitating the identification of novel molecular targets. This study aims to elucidate the role of the deubiquitinas...
Acute myeloid leukemia (AML) is a highly aggressive malignancy with frequent therapeutic resistance, necessitating the identification of novel molecular targets. This study aims to elucidate the role of the deubiquitinase OTUD5 in AML progression by regulating SLC7A11 to suppress ferroptosis. We analyzed OTUD5 expression in AML patient samples and cell lines using RNA sequencing and quantitative PCR. Functional roles were assessed through OTUD5 silencing and overexpression in AML cell lines (THP-1, HL-60), followed by proliferation, colony formation, and ferroptosis assays (ROS, labile Fe, GSH, MDA). Co-immunoprecipitation and ubiquitination assays confirmed OTUD5-SLC7A11 interactions, while xenograft models validated findings. Molecular docking and transmission electron microscopy further elucidated mechanisms. OTUD5 was significantly upregulated in AML, correlating with ferroptosis suppression. OTUD5 directly interacted with and deubiquitinated SLC7A11, enhancing its stability and promoting AML cell survival. OTUD5 silencing induced ferroptosis, marked by increased labile iron, ROS, and mitochondrial damage, which was reversed by SLC7A11 overexpression or GSH supplementation. , OTUD5 knockdown reduced tumor growth, an effect mitigated by SLC7A11 overexpression or GSH. The OTUD5-SLC7A11 axis drives AML progression by suppressing ferroptosis, offering a novel therapeutic target to exploit ferroptosis sensitivity and overcome treatment resistance in AML.
MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.
Kisielewska M, Suwała S, Drąg-Zalesińska M … +1 more , Rembiałkowska N
Cell Cycle · 2026 Dec · PMID 42290218 · Full text
Melanoma remains one of the most aggressive cancers, and although immune checkpoint blockade and MAPK-targeted therapies have transformed clinical management, durable responses occur in only a subset of patients. Converg...
Melanoma remains one of the most aggressive cancers, and although immune checkpoint blockade and MAPK-targeted therapies have transformed clinical management, durable responses occur in only a subset of patients. Converging evidence identifies microphthalmia-associated transcription factor (MITF) - dependent phenotype switching as a central, non-genetic mechanism enabling melanoma cells to escape therapy. Dynamic fluctuations in MITF activity permit transitions between differentiated, proliferative states and invasive, drug-resistant phenotypes. This review synthesizes emerging insights into the tumor microenvironmental, mechanical, and metabolic cues that regulate MITF states. These include cytokine-driven inflammatory signaling, hypoxia, cancer-associated fibroblasts, extracellular matrix remodeling, integrin - YAP/TAZ - mediated mechanotransduction, and metabolic reprogramming involving glycolysis - OXPHOS switching, lipid-regulated MITF control, and nutrient-stress responses. By integrating these pathways, MITF-dependent plasticity shapes melanoma adaptation and persistence under therapeutic pressure. Understanding this interconnected network provides a foundation for developing strategies to target phenotype switching and overcome treatment resistance.
FCGR2B drives immunosuppressive M2 polarization of tumor-associated macrophages via metabolic reprogramming of fatty acid oxidation.
Han Z, Rao P, Wang F … +4 more , Xing Y, Guo X, Du C, Wang Y
Cell Cycle · 2026 Dec · PMID 42289001 · Full text
FCGR2B, the only inhibitory receptor in the Fcγ receptor family, plays a crucial role in both innate and adaptive immunity. In this study, we observed high FCGR2B expression in tumor-associated macrophages (TAMs) induced...
FCGR2B, the only inhibitory receptor in the Fcγ receptor family, plays a crucial role in both innate and adaptive immunity. In this study, we observed high FCGR2B expression in tumor-associated macrophages (TAMs) induced by B16 melanoma cells. Knockdown of in these TAMs suppressed their M2 polarization, as evidenced by decreased expression of immunosuppressive factors, including Arg-1, IL-10, and Fizz1. Furthermore, knockdown enhanced the phagocytic and antigen-presenting capacities of TAMs, promoted ROS production, and improved their ability to kill melanoma cells in vitro. Transcriptomic analysis revealed that knockdown predominantly affected key metabolic and signaling pathways, including the JAK-STAT and PPAR-γ pathways. Using classic pharmacological inhibitors (2-DG and C75), we confirmed that FCGR2B interference remodels glycolipid metabolism in TAMs, which is characterized primarily by attenuated fatty acid metabolism, accompanied by increased glycolysis and intracellular free fatty acid accumulation. Moreover, FCGR2B interference downregulated the fatty acid oxidation key enzyme CPT1a by inhibiting the JAK/STAT6/PPAR-γ signaling axis, thereby reducing fatty acid oxidation. Concomitantly, it alleviated endoplasmic reticulum stress via the IRE1/XBP1 pathway, ultimately attenuating the tumor-promoting phenotype of TAMs. Our findings delineate a mechanism by which FCGR2B integrates metabolic and signaling pathways to regulate TAM function, providing a mechanistic basis for targeting FCGR2B in cancer immunotherapy.
RBMS1 enhances PDPK1 mRNA stability to promote multiple myeloma malignancy and M2 macrophage polarization.
Liu Y, Geng YQ, Jiang L … +1 more , Liu AC
Cell Cycle · 2026 Dec · PMID 42277590 · Full text
Multiple myeloma (MM) is an incurable malignancy of bone marrow plasma cells. Tumor-associated macrophages (TAMs) are the predominant immune cells in the bone marrow microenvironment of MM and play important roles in MM....
Multiple myeloma (MM) is an incurable malignancy of bone marrow plasma cells. Tumor-associated macrophages (TAMs) are the predominant immune cells in the bone marrow microenvironment of MM and play important roles in MM. The effect of RBMS1 on MM has not yet been reported. This study aimed to investigate the function of RBMS1 in MM. Through the analysis of GSE datasets, we identified RBMS1 as a potential pathogenic factor in MM. We further investigated the effects of RBMS1 on the proliferation of MM cells (RPMI8226, MM1S, and KMS11) and its regulation of TAM polarization. An animal model was established by intravenous injection of MM cells into 6-week-old male NOG mice. Bioinformatics analyses, including RRA, WGCNA, and GO enrichment, screened for potential pathogenic genes in MM. Kaplan - Meier survival identified RBMS1 as a prognostic marker associated with poor outcomes in MM. Functionally, RBMS1 enhanced MM cell proliferation, colony formation, and cell cycle. Moreover, RBMS1 promoted M2 polarization of macrophages, as evidenced by elevated levels of M2 macrophage markers, as well as increased CCL2 secretion. Consistently, in a male NOD/Shi-scid IL-2 Rγ mouse xenograft model, RBMS1 accelerated tumor growth and enhanced M2 macrophage polarization. Mechanistically, RBMS1 bound to the 3'UTR of PDPK1 mRNA, enhancing its stability and activating the pro-tumorigenic β-catenin signaling pathway, thereby promoting tumor growth. Collectively, this study is the first to report the functional role of RBMS1 in MM and highlights the importance of the RBMS1/PDPK1/β-catenin signaling axis in MM, providing new insights for basic research on MM.
MAGED4 promotes hepatocellular carcinoma progression via activation of JAK2/STAT3 pathway by stabilizing TRIM21.
Zhao Y, Zhang Y, Cao J … +6 more , Liu Z, Zhu R, Liang R, Wang W, Li J, Sun Y
Cell Cycle · 2026 Dec · PMID 42272063 · Full text
Melanoma-associated antigen D4 (MAGED4) belongs to the melanoma-associated antigen family and is upregulated in various cancer types. However, the functional role and molecular mechanisms of MAGED4 in hepatocellular carc...
Melanoma-associated antigen D4 (MAGED4) belongs to the melanoma-associated antigen family and is upregulated in various cancer types. However, the functional role and molecular mechanisms of MAGED4 in hepatocellular carcinoma (HCC) remain largely unknown. In this study, we observed that MAGED4 expression levels were significantly higher in HCC tissues than in non-cancerous tissues and elevated expression was associated with poor patient outcomes. Functional assays demonstrated that MAGED4 promoted proliferation and migration of HCC. We found that MAGED4 can activate the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Mass spectrometry and co-immunoprecipitation assays revealed an interaction between MAGED4 and tripartite motif-containing 21 (TRIM21). Confocal microscopy experiments confirmed the colocalization of MAGED4 with TRIM21. Mechanistically, MAGED4 can regulate the stability of TRIM21 by preventing its ubiquitination and degradation. Furthermore, MAGED4 contributes to the downregulation of suppressor of cytokine signaling 3 (SOCS3) via TRIM21, and this effect can be partially reversed by si-TRIM21 in MAGED4-overexpressing cells. These findings indicate that MAGED4 promotes HCC progression through the activation of the JAK2/STAT3 pathway by stabilizing TRIM21, suggesting that targeting MAGED4 may provide new insights into HCC treatment strategies.
Stattic administration plays a protective role in a lipopolysaccharide-induced acute lung injury cell model.
Li B, Liu C, Li H … +5 more , Sun Y, Zhang R, Liu F, Song Q, Zhang Y
Cell Cycle · 2026 Dec · PMID 42257271 · Full text
Inflammation and apoptosis are vital the processesis of acute lung injury (ALI). Signal transducer and activator of transcription 3 (Stat3) plays diverse roles in cellular processes. Little is known about the activation...
Inflammation and apoptosis are vital the processesis of acute lung injury (ALI). Signal transducer and activator of transcription 3 (Stat3) plays diverse roles in cellular processes. Little is known about the activation and function of lungs during ALI. Stat3 activation is observed during ALI. RAW264.7 cells were treated with lipopolysaccharide (LPS) to establish an ALI cell model. Stattic, a Stat3 inhibitor, was then administered to LPS-treated RAW264.7, to probe its effect on inflammation, apoptosis, and oxidative stress . Western blot analysis confirmed that Stat3 was upregulated and phosphorylated in LPS-exposed cells, while stattic administration decreased these effects. LPS treatment reduced cell viability, as evidenced by MTT, CCK-8, and colony formation assays. However, cell viability was restored after treatment with stattic. ELISA and quantitative PCR indicated that pro-inflammation cytokines, such as Interleukin-1β, IL-6, IL-8, matrix metalloproteinase-13, and tumor necrosis factor-α, were robustly elevated due to LPS stimulation; however, stattic treatment abolished the upregulation of these cytokines. Furthermore, analysis of oxidative stress effectors (malondialdehyde, glutathione, catalase, and superoxide dismutase) showed that LPS treatment upregulated oxidative stress, which was confirmed by the deactivation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1/NAD(P)H quinone dehydrogenase 1 pathway. Apoptosis in cells was also upregulated by LPS. Stattic alleviated oxidative stress and apoptosis induced by LPS. Moreover, Stat3 overexpression reversed the protective effects of stattic on cell viability, inflammation, oxidative stress, and apoptosis. Our study demonstrates that stattic treatment mitigates LPS-triggered inflammatory injury by deactivating the Jak1/Stat3 pathway in ALI.
Integrated transcriptomic and metabolomic analyses provide mechanistic insights into the pro-proliferative role of DARS in human MPN cell models.
Xiong H, Zhang H, Zhang L … +8 more , Wang X, Wan F, Li Y, Bai J, Zhang J, Wang Y, Li L, Zhang L
Cell Cycle · 2026 Dec · PMID 42177774 · Full text
Previous studies have shown that DARS is highly expressed in patients with myeloproliferative neoplasms (MPN), and these patients have higher disease burdens. However, the mechanism by which DARS promotes the proliferati...
Previous studies have shown that DARS is highly expressed in patients with myeloproliferative neoplasms (MPN), and these patients have higher disease burdens. However, the mechanism by which DARS promotes the proliferation of MPN cells remains unclear. Here, we explored the tumor-intrinsic role of DARS in human MPN cell models and the associated molecular mechanisms using an integrated multi-omics approach. DARS depletion suppressed the proliferation of MPN cells in vitro and xenograft tumor growth in vivo, induced cell-cycle arrest, and promoted apoptosis. Metabolomic analysis identified 190 differential metabolites associated with DARS depletion in MPN cells, many of which were enriched in cancer-related pathways. Transcriptomic analysis showed that DARS depletion was associated with altered expression of more than 2,000 genes; integrated analysis of transcriptomic and metabolomic data indicated potential involvement of calcium signaling, pyrimidine metabolism, and nucleotide metabolism. Re-analysis of independent public MPN datasets further supported the association of DARS with disease context and immune-infiltration features. Overall, our results support a pro-proliferative role of DARS in human MPN cell models. DARS depletion was associated with PI3K/AKT-related transcriptional and metabolic alterations, and reactivation of PI3K/AKT partially rescued the phenotypic changes induced by DARS depletion.
Amplification of pro-proliferative genes adjacent to the F3 gene in pancreatic adenocarcinoma is associated with worse outcomes.
Nidamanur S, Thomas TM, Soliman SA … +2 more , Aboujaoude MT, Blanck G
Cell Cycle · 2026 Dec · PMID 42165335 · Full text
While the elevated expression of F3 is known to contribute to a hyper-venous thromboembolism (VTE) state in pancreatic adenocarcinoma (PAAD), the basis for elevated F3 expression remains unexplored. This study investigat...
While the elevated expression of F3 is known to contribute to a hyper-venous thromboembolism (VTE) state in pancreatic adenocarcinoma (PAAD), the basis for elevated F3 expression remains unexplored. This study investigated whether amplification of the genes, ARHGAP29 and SLC44A3, which are adjacent to F3, could explain the amplification of the F3 gene. Thus, precision-guided copy number variation (CNV) analyses were performed using two PAAD data sets: Clinical Proteomic Tumor Analysis Consortium (CPTAC)-PAAD and The Cancer Genome Atlas (TCGA)-PAAD. Kaplan-Meier (KM) analyses demonstrated that patients representing the upper percentiles of CNs for ARHGAP29 and SLC44A3 had significantly worse overall survival (OS) and disease-free survival (DFS) for CPTAC-PAAD. Trends for the same outcomes for OS were observed for TCGA-PAAD. Pearson's correlation tests for ARHGAP29, F3, and SLC44A3 CNs and MSIsensor scores showed statistical significance, indicating that higher amplification was consistent with greater genomic instability. F3 CNs and the F3 CN-based outcome assessments were consistent with the outcomes based on the increased CNs for ARHGAP29 and SLC44A3, for both CPTAC-PAAD and TCGA-PAAD. These findings raise the question of whether a selection for increased CNs of pro-proliferative genes, with a corresponding increase in F3 CNs, contributes to increased VTE and worse outcomes for PAAD?
UBE2C promotes pancreatic cancer progression through PI3K/Akt/mTOR signaling pathway.
Zhou Z, Chen Y, Li P
Cell Cycle · 2026 Dec · PMID 42157383 · Full text
UBE2C, a key member of the ubiquitin-proteasome system, is overexpressed in various malignant tumors and correlates with poor prognosis. Our findings reveal that UBE2C expression is elevated in both pancreatic cancer cel...
UBE2C, a key member of the ubiquitin-proteasome system, is overexpressed in various malignant tumors and correlates with poor prognosis. Our findings reveal that UBE2C expression is elevated in both pancreatic cancer cell lines and tissues compared to normal pancreatic cells and tissues, with this aberrant expression linked to a poor prognosis. Knockdown of UBE2C expression reduces pancreatic cancer cell proliferation, migration, and invasion, while significantly decreasing the phosphorylation of the PI3K/AKT/mTOR signaling pathway. Administration of the pathway activator SC79 reverses the inhibitory effects of UBE2C knockdown on the PI3K/AKT/mTOR pathway, restoring the proliferation, migration, and invasion of pancreatic cancer cells. These results suggest that UBE2C promotes pancreatic cancer progression the PI3K/AKT/mTOR signaling pathway. Thus, UBE2C serves as a potential biomarker for the early detection and diagnosis of pancreatic cancer and may represent a promising therapeutic target.
TGFA promotes the development of cervical cancer via interacting with DSG2.
Dong C, Zhang B, Song J … +4 more , Lin Y, Wang Y, Yu J, Ma D
Cell Cycle · 2026 Dec · PMID 42154444 · Full text
This study aims to uncover the role and mechanism of transforming growth factor α (TGFA) on the malignant progression of cervical cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western...
This study aims to uncover the role and mechanism of transforming growth factor α (TGFA) on the malignant progression of cervical cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to examine the expression levels of TGFA in cancer cells and tissues. Changes in cell viability, apoptosis, and malignant metastatic ability of cancer cells were detected using methylthiazolyldiphenyl-tetrazolium bromide (MTT), flow cytometry, and Transwell method respectively. Autophagy was evaluated via microtubule-associated proteins light chain 3 (LC3) and sequestosome 1 (p62) expression. A nude mouse xenograft model was used for validation. RNA pull-down assay was performed to explore the interaction between TGFA and desmoglein 2 (DSG2). These results indicated that TGFA expression was elevated in both cervical cancer tissues and cells. TGFA overexpression promoted cell proliferation, metastasis, and autophagy, whereas TGFA knockdown exerted the opposite effects and inhibited tumor growth. Mechanistically, TGFA bound to DSG2 and affected the downstream MYC oncogene (c-MYC)/ADAM metallopeptidase domain 17 (ADAM17) pathway. In conclusion, TGFA serves as an upstream regulator of the DSG2/c-MYC/ADAM17 axis, which is correlated with autophagy and malignant progression of cervical cancer.
Polyploid giant cancer cells: the hidden players in ovarian cancer progression and prognosis.
Roy S, Rakhshit S, Chakraborty S … +4 more , Chakraborty S, Jana S, Sircar P, Nayak A
Cell Cycle · 2026 Dec · PMID 42153639 · Full text
Polyploid giant cancer cells (PGCCs) showcase a unique and often undervalued subpopulation within tumors that performs a major role in promoting the aggressiveness and therapy resistance of ovarian cancer that is one of...
Polyploid giant cancer cells (PGCCs) showcase a unique and often undervalued subpopulation within tumors that performs a major role in promoting the aggressiveness and therapy resistance of ovarian cancer that is one of the deadliest cancers. These unusually large numbers of cells, which may be multinucleated or single-nucleated, typically arise when cancer cells are exposed to different stress conditions. Their formation begins through mechanisms like endoreplication, failed cytokinesis, or disrupted cell fusion. Functionally, in ovarian cancer, these PGCCs act as "mother" cells, generating heterogeneous sets of smaller, more resilient daughter cells through depolyploidization or meiosis. This unusual and unique capability induces a significant tumor relapse and reemergence. Moreover, they drive epithelial-to-mesenchymal transition (EMT), increasing invasiveness, metastatic ability, and ovarian tumor embolization. Their identification within circulating tumor cells (CTCs) is being examined as a biomarker for worse prognosis and disease progression. Importantly, ovarian PGCCs are inherently multidrug-resistant as they escape apoptosis, re-regulate metabolic activities, and actively efflux chemotherapeutic agents into the extracellular environment. These characteristics make them notably challenging to fully eliminate with conventional therapeutic strategies. Targeting PGCCs might offer a game-changing way to overcome therapeutic resistance and improve patient outcomes in advanced ovarian cancer.
Circular RNAs in tumorigenesis: an insight into recent research in biogenesis and targeted tumor therapy.
Shafaghat Z, Golshanrad P, Saharkhiz S … +5 more , Leśniak A, Mikeladze D, Datukishvili N, Ramezani Farani M, Alipourfard I
Cell Cycle · 2026 Dec · PMID 42148803 · Full text
Circular RNAs (circRNAs) are eukaryotic RNA molecules that are covalently closed and have the characteristics of high stability, tissue-specific expression, and cell-specific expression. The majority of circRNAs are prod...
Circular RNAs (circRNAs) are eukaryotic RNA molecules that are covalently closed and have the characteristics of high stability, tissue-specific expression, and cell-specific expression. The majority of circRNAs are produced from pre-mRNAs that also result in linear RNA, and they have expression patterns that are similar to those of their host mRNAs. Despite their abundance, circRNAs are typically expressed at lower levels than mRNAs. These molecules are often dysregulated in Cancer and play important roles during the beginning and progression of tumors, according to mounting data. Dysregulated circRNAs unique to Cancer may be used as biomarkers for cancer diagnosis and prognosis since certain circRNAs from cancer tissues have been shown to go through the bloodstream and be persistently present in sera. It has been discovered that circRNAs not only influence tumor immunity and play a major role in tumor indicators, tumor development, and prognosis, but they may also be expressed improperly in various tumors.
KIBRA impairs DNA damage repair and suppresses osteosarcoma progression by inhibiting the Wnt/β-catenin signaling activity.
Zhou J, Leng Z, Guo Q … +4 more , Liu L, Wang Z, Ma J, Suonan A
Cell Cycle · 2026 Dec · PMID 42148796 · Full text
Kidney and brain expressed protein (KIBRA) has been implicated in various cancers, but its mechanisms in osteosarcoma remain poorly understood. KIBRA expression was analyzed in osteosarcoma datasets and cell lines. Funct...
Kidney and brain expressed protein (KIBRA) has been implicated in various cancers, but its mechanisms in osteosarcoma remain poorly understood. KIBRA expression was analyzed in osteosarcoma datasets and cell lines. Functional assays, including Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, wound healing, Transwell, and flow cytometry, were performed to assess proliferation, migration, invasion, and apoptosis in osteosarcoma cells after KIBRA overexpression. A subcutaneous xenograft model was established to evaluate tumor growth . DNA damage response was examined via immunofluorescence staining of the phosphorylated form of histone H2AX (γH2AX) foci and Western blot analysis of RAD51 Recombinase (RAD51) and γH2AX. KIBRA was significantly downregulated in osteosarcoma tissues and cell lines. Overexpression of KIBRA suppressed proliferation, migration, invasion, and DNA damage repair, while promoting apoptosis in osteosarcoma cells. , KIBRA overexpression inhibited tumor growth and impaired DNA damage repair, as evidenced by increased γH2AX foci and decreased RAD51 expression. Mechanistically, KIBRA inhibited the Wnt/β-catenin signaling activity, and activating this pathway by SKL2001 reversed the inhibitory effects of KIBRA on osteosarcoma progression and DNA damage repair. Therefore, KIBRA acts as a tumor suppressor in osteosarcoma by inhibiting the Wnt/β-catenin signaling activity, thereby impairing DNA damage repair and suppressing malignant progression.
Microenvironment stiffness regulates cell cycle.
Gu S, Yang Y, Lin B … +3 more , Luo Y, Zhang D, Yang J
Cell Cycle · 2026 Dec · PMID 42112591 · Full text
The cell cycle is a highly conserved and ordered process that regulates cell proliferation under physiological and pathological conditions. Among the physical properties of the cellular microenvironment, the extracellula...
The cell cycle is a highly conserved and ordered process that regulates cell proliferation under physiological and pathological conditions. Among the physical properties of the cellular microenvironment, the extracellular matrix (ECM) stiffness is a crucial regulator of cellular behavior. Emerging research suggests a strong relationship between ECM stiffness and cell cycle progression, although the underlying mechanisms remain unclear. In various diseases, including cancer, neurological disorders, and fibrosis, both ECM stiffness and the cell cycle are tightly involved, thereby influencing disease progression. In addition, ECM stiffness varies across tissues as the disease progresses. This review summarizes current findings on the mechanotransduction pathway through which microenvironmental stiffness regulates the cell cycle across different cell types and stiffness ranges. We also discuss the limitations of the current research and future directions for deepening our understanding of how physical cues in the microenvironment modulate cell cycle control.
Metformin counteracts lipid accumulation and cell proliferation in hepatocellular carcinoma via regulating METTL3-mediated mA methylation.
Qi Y, Chen C, Dai Y … +6 more , Wang Z, Liu X, Guo C, Wang M, Hu Z, Di H
Cell Cycle · 2026 Dec · PMID 42070116 · Full text
Metformin, a first-line antidiabetic drug, has demonstrated anticancer potential in various malignancies, yet its precise mechanisms in hepatocellular carcinoma (HCC) remain incompletely defined. Here, we show that metfo...
Metformin, a first-line antidiabetic drug, has demonstrated anticancer potential in various malignancies, yet its precise mechanisms in hepatocellular carcinoma (HCC) remain incompletely defined. Here, we show that metformin inhibits lipid accumulation and proliferation in HCC cells through modulation of N6-methyladenosine (mA) RNA methylation. Treatment of HepG2 and Huh7 cells with metformin significantly reduced intracellular triglyceride and cholesterol levels, concomitant with decreased lipid droplet accumulation and impaired cell proliferation. Mechanistically, metformin lowered global mA methylation by downregulating the mA methyltransferase Methyltransferase-like 3 (METTL3), while upregulating the demethylase Fat mass and obesity-associated protein (FTO). Functional assays revealed that METTL3 overexpression restored lipid accumulation and proliferation in metformin-treated cells, whereas METTL3 knockdown phenocopied the lipid-lowering and anti-proliferative effects of metformin. Further analyses identified the METTL3/ACC1/FASN axis as a critical downstream pathway, with metformin suppressing mA modification and expression of Fatty acid synthase (FASN) and Acetyl-CoA carboxylase 1 (ACC1) transcripts - effects reversed by METTL3 overexpression. These findings establish METTL3 as a central mediator of metformin's metabolic and antiproliferative activities in HCC, uncovering a previously unappreciated epitranscriptomic mechanism by which metformin impedes tumor progression.
CTDSPL2 facilitates resistance to paclitaxel in breast cancer cells by suppressing SCYL1 phosphorylation.
Zhao J, Zhao W, Wei Z … +4 more , Hou F, Sun L, Li X, Dong X
Cell Cycle · 2026 Dec · PMID 42041204 · Full text
Breast cancer (BC) exhibits significant heterogeneity and complexity and is leading causes of mortality in women globally. Paclitaxel (PTX) is commonly utilized as the primary medication for BC. However, the resistance o...
Breast cancer (BC) exhibits significant heterogeneity and complexity and is leading causes of mortality in women globally. Paclitaxel (PTX) is commonly utilized as the primary medication for BC. However, the resistance of BC to PTX poses a significant challenge in clinical treatment. This study aimed at to explore whether carboxy-terminal domain small phosphatase like 2 (CTDSPL2) affected PTX resistance in BC cells. PTX resistant BC cell lines, including MCF-7/PTX and MDA-MB-231/PTX, were developed by continuously increasing PTX concentration, and we found that CTDSPL2 was upregulated in BC cells with PTX resistance. Loss-of-function studies showed that CTDSPL2 knockdown caused a decrease in cytotoxicity and proliferative ability in PTX-resistant BC cells, as well as enhanced cell apoptotic rate and DNA damage. The results from nanoparticle tracking analysis (NTA) indicated that CTDSPL2 knockdown also suppressed the secretion of extracellular vesicles. tumorigenesis assays showed that CTDSPL2 downregulation inhibited tumorigenicity of nude mice injecting with PTX-resistant BC cells. Co-immunoprecipitation (Co-IP) assay demonstrated the binding between CTDSPL2 and SCY1-like pseudokinase 1 (SCYL1). The increased level of SCYL1 phosphorylation evoked by CTDSPL2 knockdown in PTX-resistant cancer cells was blocked after mutating the serine 754 site of SCYL1 to alanine. In conclusion, the present study identifies CTDSPL2 as a new factor in BC that plays an essential role in PTX-resistant BC cells through the regulation of SCYL1 phosphorylation.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe