Cell Division最新文献

There is evidence that atherosclerosis is a "tumor-like" disease and has similar genetic mutations to lung adenocarcinoma. In addition, the treatment and progression of lung adenocarcinoma can contribute to the development of atherosclerosis. This highlights the importance of studying the mechanisms of crosstalk between these two diseases and developing tools for early diagnosis and prognosis. We obtained gene expression profiles of both diseases through the GEO and TCGA databases and screened for crosstalk genes on the basis of differential genes. On the one hand, we constructed a diagnostic model of AS with LUAD by screening the core genes through Lasso and SVM-RFE to advance the early diagnosis of AS in patients with LUAD and explored the association between the core genes and immune infiltration. On the other hand, we constructed a robust prognostic model of LUAD based on crosstalk genes, explored the potential mechanisms of prognostic model genes in the regulation of immune infiltration and predicted treatment differences in LUAD patients to advance clinical decision-making. In addition, we constructed a PPI network based on crosstalk genes and a TF-miRNA-mRNA network, and performed drug prediction and molecular docking validation based on core targets. In conclusion, we revealed the crosstalk between AS and LUAD based on multifaceted transcriptomic analysis, screened novel targets, advanced diagnosis and prognosis, explored potential drugs and treatments, and provided invaluable insights into the research and treatment of AS with LUAD.

Cancer, as one of the main causes of human deaths, has an adverse effect on the quality of life in cancer patients. Despite many advances in diagnostic and therapeutic methods, there is still a poor prognosis in cancer patients that can be associated with the late tumor diagnosis. Therefore, investigating the molecular pathology of cancer can help to introduce early diagnostic markers. MicroRNAs (miRNAs) have key roles in regulation of cell proliferation, migration, and apoptosis. Deregulations of miRNAs have been widely reported in various cancers. Regarding the high stability of miRNAs in body fluids, they can be used as the non-invasive diagnostic markers in tumor screening programs and early detection. Considering the aberrant expression of miR-339 in a wide range of tumors, we discussed the role of miR-339 during tumor progressions. MiR-339 mainly functions as a tumor suppressor by the modulation of apoptosis, transcription factors, and signaling pathways. This review can be an effective step towards suggesting miR-339 as a therapeutic target and diagnostic marker in cancer patients.

Background: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer, with high mortality and limited treatment approaches. This paper explores the function of TAL1 in NSCLC progression and glycolysis and its mechanism.

Methods: Bioinformatics analysis screened out TAL1 and the upstream and downstream molecules. MTT, EdU, wound healing assay, Transwell assay, and TUNEL were utilized to detect the malignant phenotype of A549 and H460 cells. Western blot analysis was conducted to detect the expression of the proliferation-associated protein (Ki67), EMT-associated proteins (E-cadherin, N-cadherin), and glycolysis-associated proteins (GLUT1, LDHA, and PDK1). Cellular metabolism assays detected changes in glucose metabolites. A xenograft model was constructed, and the mouse tumor weight and volumes were measured periodically. Dual-luciferase assays and ChIP assays were performed to authenticate the transcriptional regulation of TAL1 on PKM2 and the relationship between DNMT3B and TAL1.

Results: TAL1 was lowly expressed in NSCLC, and TAL1 overexpression prevented the proliferation, migration, and invasion and elevated apoptosis. TAL1 inhibited PKM2 transcription, and overexpression of PKM2 reversed the trend of overexpression of TAL1 and promoted glycolysis. DNMT3B inhibited TAL1 expression through methylation modification. DNMT3B overexpression facilitated NSCLC cell growth and promoted glycolysis, and further overexpression of TAL1 reversed this trend. In vivo experiments showed that overexpression of TAL1 inhibited NSCLC progression, while combined overexpression of PKM2 promoted NSCLC progression. Overexpression of DNMT3B promoted NSCLC progression, and combined knockdown of PKM2 inhibited NSCLC progression.

Conclusion: DNMT3B activates glycolysis and promotes NSCLC progression by mediating methylation modification of TAL1 and inducing PKM2 transcription.

Objective: This study aims to develop a ceRNA network associated with the chromosomal passenger complex (CPC) and identify a prognostic signature in lung cancer, the most diagnosed globally, to better understand the molecular mechanisms underlying tumor progression.

Methods: The study used R packages and publicly available databases to conduct multi-omics In-silico analyses on CPC. These tools facilitated gene expression profiling, prognostic assessment, exploration of miRNA (microRNA), lncRNA (long non-coding RNA), transcription factor interactions, and pathway enrichment analysis. Molecular docking tools were used to evaluate binding affinities of CPC proteins with tobacco carcinogens, selective Aurora kinase B inhibitors, FDA-approved chemotherapeutics, and natural compounds. Immune landscape analysis was conducted using the SPRING viewer to visualize immune cell subpopulations in NSCLC, validated by correlation analysis using the GSCA database.

Results: The study reveals that CPC genes-BIRC5, CDCA8, INCENP, and AURKB-are overexpressed in lung adenocarcinoma (LUAD) and are associated with poor overall survival, especially in smokers. A dysregulated ceRNA axis involving lncRNA TMPO-AS1 and miRNA-hsa-let-7b-5p was identified, along with transcription factor E2F1, which shows a strong correlation with the CPC genes. Notably, TMPO-AS1 and E2F1 are positively correlated, while hsa-let-7b-5p is negatively correlated with the CPCs, contributing to tumor progression. Downregulation of hsa-let-7b-5p is linked to poorer outcomes, highlighting its potential as a therapeutic target. Nicotine and NNK show stable binding, suggesting potential roles in activating the CPC pathway and contributing to LUAD progression. CPCs have a strong binding affinity with Hesperidin, a natural bioflavonoid, compared to known chemotherapeutic agents like docetaxel and paclitaxel. CPC genes are negatively correlated with CD4⁺ T cells, indicating a role in promoting an immunosuppressive tumor microenvironment.

Conclusion: Lung adenocarcinoma patients have poorer prognosis due to higher levels of CPCs, TMPO-AS1, and E2F1. A sponge complex between TMPO-AS1 and hsa-let-7b-5p may contribute to the tumor progression, and targeting CPCs with natural compounds could offer therapeutic potential. Highlights 1. The overexpression of chromosomal passenger complex genes, AURKB, BIRC5, CDCA8, and INCENP is significantly associated with poor prognosis in lung adenocarcinoma (LUAD), particularly among smokers. 2. The competing endogenous RNA (ceRNA) axis, which involves the long non-coding RNA TMPO-AS1 and the miRNA hsa-let-7b-5p, regulates the expression of these CPC genes. TMPO-AS1 shows a positive correlation with CPC genes, while hsa-let-7b-5p shows a negative correlation. 3. Survival analysis indicates that the combined expression of CPC genes, TMPO-AS1, hsa-let-7b-5p, and E2F1 may serve as a reliab

Background: Overexpression or downregulation of long noncoding RNA (lncRNA) plays an essential role in the progression and chemotherapy-resistant of breast cancer (BRCA). LncPRESS1 is a lncRNA regulated by p53, suggesting its potential in participating in carcinogenesis. However, few evidences reported the role of LncPRESS1 in tumor development.

Methods: The clinical significance of LncPRESS1 was explored in BRCA and normal samples derived from the patients. Overexpression and knockdown of LncPRESS1 were performed by lentivirus. CCK-8 and colony formation were conducted to examined the proliferation ability of BRCA cells. Apoptosis was measured by PI/Annexin V staining and the activity of caspase 3/7. Xenografted tumorigenesis in nude mice was applied to explore the role of LncPRESS1 on BRCA progression and cisplatin response. RT-qPCR was used to detect the mRNA level, while immunoblotting was applied to check the protein level.

Results: In this study, we identified that LncPRESS1 was significantly upregulated in BRCA tissues as compared with normal tissues, and in the cancer tissues with late stage or node metastasis. LncPRESS1 abundance was not changed among the patients based on the expression of estrogen receptor, progesterone receptor, or epidermal growth factor 2. In vitro, LncPRESS1 suppressed the apoptosis, while enhanced the proliferation and cisplatin resistance in BRCA cells. Upregulation of LncPRESS1 was also observed in the patients who did not response to cisplatin treatment. In vivo, knockdown of LncPRESS1 suppressed the tumorigenesis of BRCA cells and enhanced the effectiveness of cisplatin. Mechanistically, LncPRESS1 activated glycolysis via upregulation of ENO1. Overexpression of LncPRESS1 dictated the sensitivity of BRCA cells to ENO1 inhibitor, ENOblock. Importantly, treatment of ENOblock reduced the resistance of cisplatin in BRCA cells with overexpression of LncPRESS1.

Conclusion: In summary, we demonstrated that LncPRESS1 facilitated BRCA progression and cisplatin resistance via activation of ENO1-mediated glycolysis. Combination of ENO1 inhibitor and cisplatin was a promising therapeutic stragtegy for BRCA patients with overexpression of LncPRESS1.

Objective: This study investigates how Fibroblast Growth Factor 4 (FGF4) drives triple-negative breast cancer (TNBC) progression by modulating macrophage polarization through the IL6/STAT3 signaling axis, with a focus on immune suppression and tumor microenvironment remodeling.

Methods: TNBC transcriptomic datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify FGF4-associated pathways using differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and immune infiltration profiling via Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Functional annotations (GO/KEGG) highlighted IL6/STAT3 as a key pathway. In vitro models with FGF4-overexpressing or knockdown TNBC cells were co-cultured with macrophages to assess IL6/STAT3 activation, M2 polarization markers (CD206, Arg1), and cytokine secretion (ELISA). Tumor cell behaviors (proliferation, migration, invasion) were quantified. In vivo orthotopic TNBC models in mice evaluated FGF4's impact on tumor growth, immune cell infiltration (flow cytometry), and STAT3 activity (Western blot).

Results: FGF4 was upregulated in TNBC and strongly correlated with M2 macrophage infiltration. In vitro, FGF4 activated IL6/STAT3 signaling, inducing macrophage polarization to an M2 phenotype with elevated IL-10/TGF-βsecretion and suppression of T cell proliferation. Conditioned media from M2 macrophages enhanced TNBC cell aggressiveness. In vivo, FGF4-overexpressing tumors showed higher weight and increased M2 markers, whereas FGF4 knockdown reduced tumor volume and enhanced CD8⁺ T cell infiltration.

Conclusion: FGF4 promotes TNBC progression by activating IL6/STAT3 to reprogram macrophages into immune-suppressive M2 effectors, fostering a tumor-permissive microenvironment. Targeting FGF4 may disrupt this crosstalk, offering a novel immunotherapeutic strategy for TNBC.

Background: Gastric cancer (GC) continues to pose a significant global health burden, necessitating a thorough understanding of the molecular mechanisms driving its progression. This study aimed to investigate the regulatory role of SMAD3 in modulating Sestrin2 ubiquitination stability and its implications in GC cell behaviors.

Methods: Leveraging GC-related single-cell transcriptomic data, we employed advanced analytical approaches to unveil the relationship between SMAD3 and Sestrin2. Experimental validations involving RT-qPCR, Western blotting, and immunofluorescence analyses elucidated the impact of SMAD3 on Sestrin2 expression and subcellular localization. In vitro models of SMAD3 overexpression and knockdown were utilized to assess the functional consequences on GC cell proliferation, migration, invasion, and apoptosis. The interaction between SMAD3 and ubiquitination-related enzymes RNF167 and STAMBPL1 was investigated through immunoprecipitation assays.

Results: Our findings revealed a positive correlation between SMAD3, Sestrin2, and STAMBPL1 expression, indicating a regulatory network within GC cells. SMAD3 was shown to stabilize Sestrin2 protein levels by influencing the ubiquitination processes of STAMBPL1 and RNF167. Functional assays demonstrated the promotion of GC cell proliferation, migration, and invasion, along with decreased apoptosis, by the SMAD3-Sestrin2 axis. Moreover, SMAD3-mediated regulation of Sestrin2 stability was found to enhance GC metastasis.

Conclusion: The study underscores the critical role of SMAD3 in modulating Sestrin2 expression and stability, consequently impacting GC cell behaviors and metastatic potential. The SMAD3-Sestrin2 axis emerges as a promising therapeutic target for GC treatment.

Background: FAM83A plays a significant role in the development of non-small cell lung cancer (NSCLC). This study elucidated the biological role of FAM83A in ferroptosis and cisplatin (DDP) sensitivity in NSCLC cells.

Methods: The expression patterns of FAM83A and TFAP2A were analyzed by bioinformatic analysis. mRNA and protein levels were detected by quantitative PCR, immunoblotting, and immunohistochemistry, respectively. Cell invasion, migration, and viability were assessed by transwell, wound healing, CCK-8 assays, respectively. Cell ferroptosis was evaluated by measuring the levels of ROS, Fe²⁺, MDA, GSH, and SOD. Chromatin immunoprecipitation (ChIP) and luciferase assays were used to confirm the relationship between TFAP2A and the FAM83A promoter. Xenograft models were generated to evaluate the role of TFAP2A in vivo.

Results: FAM83A and TFAP2A levels were upregulated in human NSCLC. FAM83A inhibition decreased NSCLC cell growth, motility, and invasiveness, while inducing ferroptosis and enhancing DDP sensitivity. Mechanistically, TFAP2A regulated FAM83A transcription in NSCLC cells. TFAP2A depletion suppressed the malignant behaviors of NSCLC cells and augmented their sensitivity to ferroptosis and DDP, and these effects were reversed by the upregulation of FAM83A. Additionally, TFAP2A depletion decreased the growth of A549 subcutaneous xenografts in vivo. Moreover, the TFAP2A/FAM83A cascade regulated the activation of the PI3K/AKT and Wnt/β-catenin pathways.

Conclusion: Our study demonstrates that the novel TFAP2A/FAM83A cascade modulates ferroptosis and drug sensitivity in NSCLC.

Background: Prostate cancer (PCa) is a common leading cause of death worldwide and is recognized as the second most frequently diagnosed cancer in the male population, making it a significant focus of long-term oncological research. The HOXD13 gene, belonging to the HOX gene family, has been associated with various malignancies, including breast and colon cancer, and is associated with prognostic outcomes. However, its specific role in prostate cancer remains to be elucidated.

Methods: The correlation of HOXD13 expression in PCa was analyzed by UALCAN database. qRT-PCR and western blot assays were employed to assess the expression levels of HOXD13 in several prostate cancer cell lines. Construct siRNA and overexpression plasmids for HOXD13 and transfect them into cells. Western blot was used to assess the knockdown efficiency of HOXD13 in the cells. The influence of HOXD13 expression on cell proliferation in PC-3 M and C4-2 cells was assessed by EDU staining. The role of HOXD13 in cell migration and invasion of prostate cancer cells was detected by wound healing and transwell assay. Western blot analysis was performed to examine apoptosis-related proteins (C-caspase3, Bax, and Bcl-2) in PC-3 M cells. The co-immunoprecipitation (Co-IP) assay evaluates the interaction between MDM2 and p53.

Results: An examination of the data obtained from the UALCAN database reveals that HOXD13 was significantly reduced in prostate cancer tissues and correlated with patient survival. In prostate cancer cell lines, notably PC-3M, HOXD13 expression was markedly reduced. Knockdown of HOXD13 promotes PC-3 M and C4-2 cells proliferation, migration, and invasion. However, the elevated expression of HOXD13 hampers PC-3 M and C4-2 cells proliferation, migration, and invasion. Furthermore, knockdown of HOXD13 in PC-3 M cells resulted in decreased levels of apoptosis markers, including C-caspase-3 and Bax. Co-immunoprecipitation assays demonstrated that HOXD13 depletion enhanced the association between MDM2 and p53.

Conclusion: HOXD13 was a critical regulator in the pathogenesis of prostate cancer, modulating the MDM2/p53 signaling pathway to promote apoptosis.