Cell Division最新文献

Colorectal cancer (CRC) is the third most common malignant tumor worldwide and is characterized by high incidence and mortality rates. In the chemotherapeutic treatment of CRC, antiangiogenic therapy is utilized throughout the entire disease course, particularly for highly metastatic tumors. However, studies have reported that resistance to current antiangiogenic therapies often develops, leading to suboptimal clinical outcomes. Vasculogenic mimicry (VM) represents a novel tumor blood supply mechanism that is distinct from traditional endothelial cell-dependent vasculature. VM channels are composed solely of tumor cells and extracellular basement membranes, emerge within malignant tumors requiring blood perfusion, and have been identified in numerous solid tumors. Research indicates that tumors exhibiting VM demonstrate greater proliferative, invasive, and metastatic potential, along with poorer prognosis, than those without VM. Additionally, studies suggest that VM contributes to the limited efficacy and resistance observed with antiangiogenic drugs in clinical practice. Thus, targeting VM is crucial in oncology, especially in CRC. Recent advances have been made in anti-VM drug therapy for CRC. Moving forward, combining VM-targeted strategies with conventional antiangiogenic therapies targeting endothelial cells may represent a promising new direction in CRC treatment. This review summarizes current insights into the mechanisms of VM in CRC and its therapeutic advancements, aiming to provide novel perspectives for clinical management.

Background: MicroRNA-124-3p (miR-124-3p) has been widely reported as an important tumor-suppressive regulator in multiple malignancies. Nevertheless, its precise biological function in stomach adenocarcinoma (STAD) remains insufficiently clarified.

Methods: We applied large-scale bioinformatics interrogation of The Cancer Genome Atlas (TCGA) STAD cohort, combined with in vitro cellular assays and in vivo xenograft experiments, to explore both the biological significance and molecular mechanisms of miR-124-3p in STAD progression.

Results: MiR-124-3p expression was significantly downregulated in STAD tissues and correlated with advanced pathological stage, poor prognosis, and reduced survival outcomes. Functional investigations confirmed that miR-124-3p directly interacts with the 3'-UTR of the aryl hydrocarbon receptor (AHR) mRNA, suppressing its expression and inducing autophagy. This regulation led to impaired proliferation, migration, and invasiveness of STAD cells. Restoration of AHR expression reversed these tumor-suppressive effects. Moreover, in vivo delivery of miR-124-3p inhibited tumor growth and mitigated cancer-induced cachexia in nude mice.

Conclusion: These findings establish miR-124-3p as a key suppressor of STAD progression via AHR-mediated autophagy, underscoring its promise as both a diagnostic biomarker and a therapeutic candidate.

Background: Long noncoding RNAs (lncRNAs) are key regulators in cancer progression. Among them, KCNMB2 antisense RNA 1 (KCNMB2-AS1) has been identified as an oncogenic lncRNA in several tumor types; however, its role in clear-cell renal cell carcinoma (ccRCC) remains largely unexplored. This study aimed to elucidate the expression profile, functional significance, and underlying molecular mechanisms of KCNMB2-AS1 in ccRCC.

Methods: The expression of KCNMB2-AS1 in ccRCC tissues and cell lines was analyzed using publicly available datasets, quantitative real-time PCR, and Western blotting. Functional assays including Cell Counting Kit-8, colony formation, wound healing, and Transwell migration/invasion tests along with in vivo xenograft experiments were performed to assess its biological effects. Mechanistic studies, including luciferase reporter, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and rescue assays, were conducted to verify the regulatory interactions among KCNMB2-AS1, forkhead box protein 3 (FOXP3), microRNA-744-3p (miR-744-3p), and cluster of differentiation 1D (CD1D).

Results: KCNMB2-AS1 expression was markedly elevated in ccRCC tissues compared to adjacent normal tissues, and its high expression was significantly associated with advanced tumor stage, presence of distant metastasis, and poor overall survival. Silencing KCNMB2-AS1 markedly suppressed ccRCC cell proliferation, migration, and invasion in vitro, accompanied by reduced epithelial-mesenchymal transition marker expression. Consistent with these findings, xenograft experiments confirmed that KCNMB2-AS1 knockdown attenuated tumor growth in vivo, while its overexpression promoted aggressive tumor behavior. Mechanistically, FOXP3 directly bound to the promoter region of KCNMB2-AS1, activating its expression transcriptionally. KCNMB2-AS1 acted as a molecular sponge for miR-744-3p, thereby relieving its inhibitory effect on CD1D expression. Rescue assays demonstrated that restoring CD1D expression counteracted the inhibitory phenotypes resulting from KCNMB2-AS1 silencing.

Conclusion: KCNMB2-AS1 serves as an oncogenic lncRNA in ccRCC, functioning through a FOXP3/KCNMB2-AS1/miR-744-3p/CD1D signaling axis, thereby revealing a novel molecular pathway that contributes to ccRCC progression.

Background: Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer deaths. Standard therapeutic management is faced with challenges like treatment resistance and late-stage diagnosis, highlighting a need for better diagnosis. LncRNAs are crucial in CRC progression and may serve as non-invasive biomarkers. For the first time, this study explores LINC00332 potential as a therapeutic and diagnostic marker in CRC.

Methods: Eighty fresh normal and tumor tissues were enrolled to evaluate the levels of LINC00332 expression using Real-time PCR method. LINC00332 ectopic expression was also done to evaluate its role in drug resistance and cell migration in HCT116 cells.

Results: Ectopic expression of LINC00332 significantly induced NOTCH and WNT pathways in HCT116 cells. LINC00332 promoted EMT process through up regulation of Vimentin, CDH2, Snail, ZEB2, Slug, MMP10, and MMP3 while down regulation of CDH1 and OCLUDIN in HCT116 cells. LINC00332 significantly induced the HCT116 cell migration and paclitaxel (PTX) resistance in HCT116 cells (p < 0.0001). There was significant up regulation of LINC00332 in CRC clinical samples compared to normal margins (p = 0.042). There was significant up regulation of LINC00332 in stage I/II tumors that was located in transverse and left colon in comparison to right colon (p = 0.03). Tumors with perineural invasion had significant LINC00332 up regulation compared with negative ones in CRC patients (p = 0.02).

Conclusions: LINC00332 promotes PTX resistance and EMT in CRC via WNT and NOTCH pathways activation. It can also be suggested as a potential diagnostic marker in early-stage CRC patients. Targeting LINC00332 may enhance PTX response, warranting further studies for therapeutic application.

Objective: BUB1, a key mitotic checkpoint kinase, is often dysregulated in cancer, yet its regulatory mechanism remains unclear. This study investigates the BUB1-centered miRNA-lncRNA-mRNA (ceRNA) network, its role in cell cycle regulation and immune modulation.

Methods: Prognostic significance and expression profiles were assessed using TCGA-based databases such as KM Plotter, UALCAN, OncoDB, ENCORI, GEPIA2, Lung Cancer Explorer, and TCGAnalyzeR. Transcription factors were identified via Enrichr, and a ceRNA network was constructed using miRNet. Binding affinity and folding energy between BUB1, miRNA, and lncRNA were predicted using miRWalk and RNA22v2. Molecular docking evaluated interactions with natural compounds, chemotherapeutics, and inhibitor. Immune subpopulations were visualized using the SPRING viewer and correlation analysis with the immune cells was conducted using the GSCA and TIMER2.0 databases.

Results: BUB1 overexpression correlated with poor LUAD prognosis, especially in smokers (HR = 1.76), with transcriptomic analysis showing a 2.46 log2-fold increase in BUB1 transcript levels in tumor. TF-E2F1 and lncRNA-TMPO-AS1 were positively correlated with BUB1 (R = 0.664 and R = 0.632, respectively), while miRNA hsa-let-7b-5p showed a negative correlation (R = - 0.366). TMPO-AS1 exhibited an inverse association with hsa-let-7b-5p, suggesting a molecular sponge formation, repressing its tumor-suppressive activity. Docking revealed strong binding affinity of hesperidin (- 9.4 kcal/mol) with BUB1. Additionally, BUB1 expression negatively correlated with CD4⁺ T cells, suggesting an immunosuppressive role.

Conclusion: This study identifies the BUB1/E2F1/TMPO-AS1/hsa-let-7b-5p axis as a potential prognostic biomarker and therapeutic target in LUAD. Targeting hsa-let-7b-5p may modulate this network, offering opportunities for both diagnostic and prognostic interventions.

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