Cell Cycle最新文献

Previous studies demonstrated that integrase-strand-transfer-inhibitors (INSTIs) promote adipocyte differentiation, while nucleoside-reverse-transcriptase-inhibitors (NRTIs) tenofovir-alafenamide-fumarate (TAF) and tenofovir-disoproxil-fumarate (TDF), inhibit adipogenesis. NRTIs were shown to counteract the pro-adipogenic effects of INSTIs[6]. However, the effects of non-nucleoside-reverse-transcriptase-inhibitors (NNRTIs) and of the novel long-acting INSTI cabotegravir (CAB), on adipogenesis, alone or in combination with NRTIs or other INSTIs, remain unclear. This study aims to elucidate the impact of NNRTIs and recent INSTIs on adipogenesis. 3T3-L1 cells were used as an adipogenesis in vitro model. The NNRTIs doravirine (DOR) and rilpivirine (RPV) were tested alone and in combination with DTG, CAB, TDF, TAF. Adipogenesis was assessed by Oil-Red-O-staining and by measuring expression-levels of peroxisome-proliferator-activated-receptor-gamma (PPARγ) and CCAAT/enhancer-binding-protein-alpha (C/EBPα). Moreover, Fibroblast-marker ER-TR7 was assessed by immunohistochemistry. CAB, DOR, and RPV promoted adipogenesis, with CAB and DOR showing greater effects. In combination, NNRTIs enhanced the adipogenic effects of CAB and DTG. Conversely, TAF and TDF, when paired with RPV or DOR, inhibited adipogenesis. NNRTIs and CAB increased ER-TR7 expression, suggesting fibroblastic differentiation. Finally, NNRTIs and INSTIs promote adipogenesis and induce fibroblastic features in 3T3-L1 cells. Contrarily, TAF and TDF exhibited an antagonistic effect on adipogenesis when combined with certain antiretrovirals, supporting our previous research.

Cell cycle arrest in dermal fibroblasts is a critical biological process essential for maintaining skin homeostasis and serves as a central mechanism driving various skin pathologies. This review systematically summarizes the endogenous and exogenous factors triggering cell cycle arrest in dermal fibroblasts and their underlying molecular mechanisms, with a particular focus on the roles of key signaling pathways such as p53, TGF-β/Smad, and Wnt/β-catenin. Additionally, the dual effects of cell cycle arrest on the skin are discussed: transient arrest facilitates DNA damage repair and tissue regeneration, whereas prolonged arrest leads to cellular senescence, chronic inflammation, collagen degradation, and fibrosis. Advances in chemical compounds modulating cell cycle arrest are also highlighted, including potential therapeutic strategies for promoting or relieving cell cycle arrest. This review provides new insights into skin regenerative medicine and anti-aging therapies while identifying critical scientific questions for future research.

The transforming growth factor-beta (TGF-β)/SMAD signaling pathway, mitogen-activated protein kinase (MAPK) signaling cascade, and dopamine receptor activity are all implicated in tumor progression. This study investigates molecular interactions among these pathways, identifying MAPK proteins that bridge SMAD and dopamine signaling in the context of breast cancer pathogenesis. A cohort of 405 breast cancer patients was categorized into molecular subtypes: luminal A (n = 130), luminal B HER2-negative (n = 100), luminal B HER2-positive (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (TNBC; n = 43). Transcriptomic profiling using microarrays and bioinformatics-based network analysis revealed differentially expressed genes across subtypes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate 11 key transcripts, and protein expression was quantified by enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) regulatory interactions were analyzed to assess post-transcriptional modulation. Among 167 differentially expressed genes, 14 were consistently altered across all subtypes. These included cell division cycle 42 (CDC42), KRAS proto-oncogene, GTPase (KRAS), and transforming growth factor beta 1 (TGFB1), which were upregulated, as well as fibroblast growth factor 2 (FGF2), fibroblast growth factor 7 (FGF7), and insulin-like growth factor 1 (IGF1), which were downregulated. miRNA analysis revealed miR-221, miR-222, and miR-16-5p as regulators of these pathways. ELISA confirmed reduced KIT, IGF1, and FGF family proteins in tumor tissues, with KRAS significantly upregulated. Protein interaction analysis highlighted key hubs linking MAPK, SMAD, and dopamine signaling. This study elucidates crucial molecular intersections between MAPK, SMAD, and dopamine pathways, identifying potential biomarkers and therapeutic targets for breast cancer.

To explore functions and mechanisms in gastric cancer (GC) progression. The mRNA and protein levels of NSUN2 and phosphoglycerate kinase 1 (PGK1) were determined by qRT-PCR and western blot. Cell proliferation, apoptosis, invasion and stemness were examined using CCK8 assay, EdU assay, flow cytometry, transwell assay and sphere formation assay. Cell glycolysis was evaluated by detecting glucose consumption, lactate production and ATP/ADP ratio. The interaction between PGK1 and NSUN2 or YBX1 was evaluated using MeRIP assay or RIP assay. Actinomycin D treatment assay was used to detect the effect of NSUN2 or YBX1 knockdown on PGK1 mRNA stability. The protein levels of p-PI3K/PI3K and p-AKT/AKT were tested by western blot. Animal study was performed to confirm the effect of NSUN2/PGK1 axis on GC tumorigenesis. NSUN2 was confirmed to be upregulated in GC tissues and cells. NSUN2 silencing could repress GC cell growth, invasion, stemness and glycolysis. NSUN2 enhanced PGK1 mRNA stability through promoting its m5C modification, and this modification could be recognized by YBX1. Besides, PGK1 overexpression reversed the inhibitory effect of NSUN2 knockdown on GC cell growth, invasion, stemness and glycolysis. In addition, NSUN2/PGK1 axis increased the activity of PI3K/AKT pathway. Animal study revealed that interference of NSUN2 reduced GC tumorigenesis via inactivating the PGK1/PI3K/AKT pathway. NSUN2/PGK1 axis might play a vital role in GC development.

Circular RNA (circRNA) is involved in the occurrence of many cancers. Nonetheless, the mechanism of circ_0003998 in non-small cell lung cancer (NSCLC) needs to be studied in depth. Real-time quantitative PCR (RT-qPCR) was carried out to check the expression of circ_0003998, microRNA-330-5p (miR-330-5p), chemokine (C-X-C motif) ligand 3 (CXCL3) and methyltransferase-3 (METTL3) in NSCLC tissues and cells. CXCL3, Vimentin and E-cadherin protein levels were measured by western blot. The functions of circ_0003998 in NSCLC cell proliferation, apoptosis, angiogenesis, migration and invasion were tested by clone formation assay, flow cytometry, tube formation assay, wound healing assay, and transwell assay in vitro. The dual-luciferase reporter assay was made to verify the relationship between miR-330-5p and circ_0003998 or CXCL3. Finally, animal experiment was made to further research the function of circ_0003998 on tumor formation in vivo. The interaction between circ_0003998 and METTL3 was analyzed by RNA Immunoprecipitation (RIP) assay, methylated RNA Immunoprecipitation (MeRIP) assay and dual-luciferase reporter assay. In NSCLC tissue and cells, circ_0003998 was markedly overexpressed. Circ_0003998 suppression inhibited NSCLC cell growth, angiogenesis, migration and invasion. Circ_0003998 sponged miR-330-5p, and miR-330-5p inhibitor could reverse the suppression effect of circ_0003998 knockdown on NSCLC cell behaviors. CXCL3 was a downstream target gene of miR-330-5p, and CXCL3 overexpression also reversed the suppressive effect of miR-330-5p on NSCLC cell behaviors. Interference of circ_0003998 reduced NSCLC tumorigenesis by regulating miR-330-5p/CXCL3 axis. Also, METTL3 promoted the expression of circ_0003998 by m6A modification. METTL3-modified circ_0003998 promoted NSCLC cell malignancy through miR-330-5p/CXCL3 axis, suggesting that circ_0003998 might be a new treatment strategy for NSCLC.

Hepatocellular carcinoma (HCC) is characterized by high metastatic potential and poor prognosis. Ring finger protein 220 (RNF220) has been implicated in tumorigenesis across various cancers; however, its role and associated regulatory mechanisms in HCC remain unclear. In this study, analysis of The Cancer Genome Atlas (TCGA) database revealed that RNF220 expression was significantly elevated in liver hepatocellular carcinoma (LIHC) tissues and was associated with poor prognosis. Further experiments confirmed the upregulation of RNF220 mRNA and protein in HCC tissues. Functional assays demonstrated that RNF220 overexpression promoted cell proliferation, migration and stemness, whereas RNF220 knockdown suppressed these processes in HCC cells. Mechanistically, RNF220 enhanced ubiquitin-specific protease 22 (USP22) expression, leading to activation of the protein kinase B (Akt) pathway. Furthermore, the knockdown of RNF220 inhibited HCC progression, an effect that could be reversed by SC79 (an Akt activator), an Akt activator. In vivo experiments further confirmed that RNF220 aggravated tumor growth and metastasis. In summary, these findings indicate that RNF220 promotes HCC progression by regulating USP22 and activating the Akt pathway, suggesting that RNF220 may serve as a potential biomarker and therapeutic target for HCC.

Cancer cells frequently undergo stresses like hypoxia, glucose deprivation, and calcium depletion, leading to protein misfolding and accumulation of unfolded proteins in the ER, which trigger ER stress. The unfolded protein response (UPR) is activated by endoplasmic reticulum (ER) stress to restore protein homeostasis by regulating protein synthesis and degradation. This review explores the multifaceted role of UPR in tumor growth, chemoresistance, and immune evasion in gynecological cancers, particularly ovarian, endometrial, and cervical cancers. UPR-associated genes have been reported to have a potential role as disease biomarkers and therapeutic targets, thus improving early detection and personalized treatment. This review aims to give insights into the role of UPR pathway in gynecological cancers and offers new perspectives for future research and clinical applications.

Epithelial carcinoma cells require penetration of the basement membrane (BM) to metastasize. The BM is a thin layer of extracellular matrix beneath epithelial and endothelial tissues. It acts as a structural barrier, preventing cancer cells from invading and undergoing endocytosis and exocytosis. Thus, understanding the relationship between the BM and tumor immunity can lead to new strategies for halting cancer progression and metastasis. Gene expression data of 33 cancers were obtained from the Cancer Genome Atlas database. The study analyzed the correlation between BM regulatory genes, copy number variations, immune-related genes, and tumor immune dysfunction rejection (TIDE). Immunohistochemical methods were used to analyze the expression of regulatory genes. And the BM score was calculated using single-sample gene set enrichment analysis. Single-cell transcriptional sequencing determined the activation status of the BM in the tumor microenvironment. The expression of BM-related genes (BMGs) exhibited significant heterogeneity across different cancer types. Most genes were up-regulated in tumor tissues. Major single nucleotide polymorphisms of BMGs included missense mutations, while major copy number variations were heterozygous deletion and heterozygous amplification. Additionally, the expressions of immune checkpoint molecules CD276, NRP1, and C10orf54 showed positive correlations with BMS. Numerous tumors displayed a significant positive correlation between BMS and TIDE scores. We demonstrate that BM regulatory genes undergo alterations specific to different cancer types, which are associated with the expression of immune checkpoints and immune dysfunction. This indicates that BM remodeling plays an active role in modulating immune resistance, rather than being a passive structural alteration.