Epithelial-mesenchymal Transformation Research Articles

Identifying Diffuse Glioma Subtypes Based on Pathway Enrichment Evaluation.

Gliomas are highly heterogeneous in molecular, histology, and microenvironment. However, a classification of gliomas by integrating different tumor microenvironment (TME) components remains unexplored.Based on the enrichment scores of 17 pathways involved in immune, stromal, DNA repair, and nervous system signatures in diffuse gliomas, we performed consensus clustering to uncover novel subtypes of gliomas. Consistently in three glioma datasets (TCGA-glioma, CGGA325, and CGGA301), we identified three subtypes: Stromal-enriched (Str-G), Nerve-enriched (Ner-G), and mixed (Mix-G). Ner-G was charactered by low immune infiltration levels, stromal contents, tumor mutation burden, copy number alterations, DNA repair activity, cell proliferation, epithelial-mesenchymal transformation, stemness, intratumor heterogeneity, androgen receptorexpression and EGFR, PTEN, NF1 and MUC16 mutation rates, while high enrichment of neurons and nervous system pathways, and high tumor purity, estrogen receptor expression, IDH1 and CIC mutation rates, temozolomide response rate and overall and disease-free survival rates. In contrast, Str-G displayed contrastive characteristics to Ner-G. Our analysis indicates that the heterogeneity between glioma cells and neurons is lower than that between glioma cells and immune and stromal cells. Furthermore, the abundance of neurons is positively associated with clinical outcomes in gliomas, while the enrichment of immune and stromal cells has a negative association with them. Our classification method provides new insights into the tumor biology of gliomas, as well as clinical implications for the precise management of this disease.

TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease

Thioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease (DKD). However, the potential mechanism of TXNIP in DKD is not yet well understood. In this study, we found that TXNIP knockout suppressed renal fibrosis and activation of mammalian target of rapamycin complex 1 (mTORC1) and restored transcription factor EB (TFEB) and autophagy activation in diabetic kidneys. Simultaneously, TXNIP interference inhibited epithelial-to-mesenchymal transformation (EMT), collagen I and fibronectin expression, and mTORC1 activation, increased TFEB nuclear translocation, and promoted autophagy restoration in HK-2 cells exposed to high glucose (HG). Rapamycin, an inhibitor of mTORC1, increased TFEB nuclear translocation and autophagy in HK-2 cells under HG conditions. Moreover, the TFEB activators, curcumin analog C1 and trehalose, effectively restored HG-induced autophagy, and abrogated HG-induced EMT and collagen I and fibronectin expression in HK-2 cells. Taken together, these findings suggest that TXNIP deficiency ameliorates renal fibrosis by regulating mTORC1/TFEB-mediated autophagy in diabetic kidney diseases.

GGT5 facilitates migration and invasion through the induction of epithelial–mesenchymal transformation in gastric cancer

BackgroundGamma-glutamyltransferase 5 (GGT5), one of the two members in the GGT family (GGT1 and GGT5), plays a crucial role in oxidative regulation, inflammation promotion, and drug metabolism. Particularly in the tumorigenesis of various cancers, its significance has been recognized. Nevertheless, GGT5’s role in gastric cancer (GC) remains ambiguous. This study delves into the function and prognostic significance of GGT5 in GC through a series of in vitro experiments.MethodsEmploying online bioinformatics analysis tools such as The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Kaplan–Meier plotter, and cBioPortal, we explored GGT5 characteristics and functions in GC. This encompassed aberrant expression, prognostic value, genomic alterations and mutations, immune cell infiltration, and associated signaling pathways. Immunohistochemistry was conducted to assess GGT5 expression in GC and adjacent normal tissues. Subsequently, univariate and multivariate logistic regression analyses were applied to investigate the associations between GGT5 and clinical characteristics. CCK8, wound healing, and migration assays were utilized to evaluate the impact of GGT5 on cell viability and migration. Additionally, Gene Set Enrichment Analysis (GSEA) and Western blot analysis were performed to scrutinize the activity of the epithelial–mesenchymal transformation (EMT) signaling pathway under GGT5 regulation.ResultsGGT5 exhibits upregulation in gastric cancer, with its overexpression significantly linked to histological differentiation in GC patients (P < 0.05). Multivariate analysis indicates that elevated GGT5 expression is an independent risk factor associated with poorer overall survival in gastric cancer patients (P < 0.05). In vitro experiments reveal that downregulation of GGT5 hampers the proliferation and migration of GC cell lines. Finally, GSEA using TCGA data highlights a significant correlation between GGT5 expression and genes associated with EMT, a finding further confirmed by Western blot analysis.ConclusionsGGT5 emerges as a promising prognostic biomarker and potential therapeutic target for GC.

Waterpipe smoke condensate induces epithelial-mesenchymal transformation and promotes metastasis of oral cancer by FOXD1 expression

Background/purposeSmoking is a major contributor to global oral cancer cases, necessitating urgent intervention. FOXD1, involved in developmental processes and various cancers, shows promise as a prognostic marker in oral squamous cell carcinoma (OSCC). This study investigates the impact of waterpipe smoke condensate (WPSC) on OSCC, focusing on FOXD1 role in inducing epithelial-mesenchymal transition (EMT) and metastasis. MethodsThe study involved using OSCC cells treated with WPSC to evaluate their proliferation, colony formation, gene expression, and protein levels. The researchers also explored the clinical relevance of their findings using online databases to analyze FOXD1 expression in cancer tissues and its correlation with clinicopathological features and patient survival. Additionally, in silico tools were employed for functional analysis, pathway enrichment, and network exploration. ResultsThe study found that WPSC increased the expression of FOXD1 in OSCC cells, which led to increased cell growth. The study also showed that FOXD1 plays a critical role in the EMT process induced by WPSC, as evidenced by changes in the expression of EMT-related genes and proteins. Clinical analysis revealed that FOXD1 was significantly associated with more aggressive tumor features and poorer prognosis in cancer patients. ConclusionThe study highlights FOXD1 as a key player in OSCC pathogenesis and a potential prognostic marker and therapeutic target, particularly when influenced by WPSC exposure. Further research is needed to explore FOXD1 molecular mechanisms and clinical implications to enhance OSCC treatment strategies.

Research Progress of circRNAs during Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

Hepatocellular carcinoma is prone to invasion and metastasis. It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate. Epithelial-mesenchymal transformation (EMT) is a key factor in promoting tumor cell invasion and metastasis. Circular RNA (circRNA) is involved in regulating EMT in hepatocarcinoma cells through multiple pathways, thereby affecting the occurrence and progression of hepatocellular carcinoma. This article mainly reviews the research progress of circRNA related to EMT core transcription factors, circRNA that promotes EMT in liver cancer, and circRNA that inhibits EMT in liver cancer.

The role of PI3K/Akt signaling pathway in chronic kidney disease.

Chronic kidney disease (CKD), including chronic glomerulonephritis, IgA nephropathy and diabetic nephropathy, are common chronic diseases characterized by structural damage and functional decline of the kidneys. The current treatment of CKD is symptom relief. Several studies have reported that the phosphatidylinositol 3 kinases (PI3K)/protein kinase B (Akt) signaling pathway is a pathway closely related to the pathological process of CKD. It can ameliorate kidney damage by inhibiting this signal pathway which is involved with inflammation, oxidative stress, cell apoptosis, epithelial mesenchymal transformation (EMT) and autophagy. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in CKD-induced inflammatory response, apoptosis, autophagy and EMT. We also summarize the latest evidence on treating CKD by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of CKD, and identify potential challenges in developing these clinical therapeutic CKD strategies, and provide appropriate solutions.

Inhibition of PD-L1 expression in non-small cell lung cancer may reduce vasculogenic mimicry formation by inhibiting the epithelial mesenchymal transformation process

Non-small cell lung cancer (NSCLC) is a kind of highly malignant tumor. Studies have shown that Vasculogenic mimicry (VM) may be responsible for dismal prognosis in NSCLC. Immunotherapy with programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) has significantly altered the treatment of assorted cancers, including NSCLC, but its role and mechanism in the formation of Vasculogenic mimicry (VM) in NSCLC remains unclear. This study aimed to investigate the role of the anti-PD-L1 antibody in the formation of VM in NSCLC and its possible mechanisms. The results showed that anti-PD-L1 antibody therapy could inhibit the growth of NSCLC-transplanted tumors and reduce the formation of VMs. In addition, this study found that anti-PD-L1 antibodies could increase the expression of the epithelial-mesenchymal transition (EMT) related factor E-cadherin. zinc finger E-box binding homeobox 1 (ZEB1) is an important transcription factor regulating EMT. Knocking down ZEB1 could significantly inhibit tumor growth, as well as the expression of VE-cadherin and mmp2, while remarkably increase the expression of E-cadherin. During this process, the formation of VM was inhibited by knowing down ZEB1 in both in vitro and in vivo experiments of the constructed ZEB1 knockdown stable transfected cell strains. Therefore, in this study, we found that anti-PD-L1 antibodies may reduce the formation of VMs by inhibiting the EMT process.

Establishment and characterization of the gemcitabine-resistant human gallbladder cancer cell line NOZ GemR.

Patients with gallbladder cancer (GBC) generally receive gemcitabine as the standard treatment; however, its efficacy is often limited owing to the development of resistance. To identify the mechanisms underlying gemcitabine resistance in GBC, a gemcitabine-resistant GBC cell line (NOZ GemR) was established by exposing the parental NOZ cell line to increasing concentrations of gemcitabine. Morphological changes, growth rates, and migratory and invasive capabilities were evaluated. Protein expression was detected using western blotting. The results demonstrated that the IC50 of NOZ and NOZ GemR was 0.011 and 4.464μM, respectively, and that the resistance index ratio was 405.8. In comparison, NOZ GemR cells grew slower and had significantly lower migration and invasion abilities than NOZ cells. There were altered levels of epithelial-mesenchymal transformation markers in NOZ GemR cells, as well as increased levels of the Akt/mTOR pathway protein. The NOZ GemR cell line could be used as an effective in vitro model to improve our understanding of gemcitabine resistance in GBC.

Effect of CHRDL1 on angiogenesis and metastasis of colorectal cancer cells via TGF-β/VEGF pathway.

Colorectal cancer (CRC) is a common digestive tract tumor with the third incidence and death in the world. There is still an urgent need for effective therapeutic targets and prognostic markers for CRC. Herein, we report a novel potential target and marker, Chordin like-1 (CHRDL1). The function of CHRDL1 has been reported in gastric cancer, breast cancer, and oral squamous cell carcinoma. However, the biological effect of CHRDL1 in CRC remains unrevealed. Transwell and tube formation experiments were used to determine the biological function of CHRDL1. Western blot and rescue experiments were used to determine the specific mechanisms of CHRDL1. Results showed CHRDL1 is significantly downregulated in CRC cell lines and tissues. In vitro, experiments confirmed that CHRDL1 can inhibit cell growth, migration, invasion, angiogenesis and reverse epithelial-mesenchymal transformation. In vivo, experiments proved that it can inhibit tumor growth and metastasis. Mechanistically, we newly find that CHRDL1 exerts biological functions through the transforming growth factor-beta (TGF-β)/vascular endothelial growth factor signaling axis in vitro and in vivo. Therefore, we concluded that CHRDL1 reduces the growth, migration, and angiogenesis of CRC cells by downregulating TGF-β signaling. Our new findings on CHRDL1 may provide a basis for clinical antiangiogenesis therapy and the prognosis of CRC.

Research Progression in the Mechanism of Bone Metastasis and Bone-Targeted Drugs in Prostate Cancer

Prostate cancer is a particularly slow growing cancer, the early stage of the disease is not easy to detect, the some major clinical manifestations include low back pain, urgent and frequent urination, urinary pain, and other urethral symptoms. These symptoms are often experienced after surgical resection or drug castration treatment. Early-stage, prostate cancer is curable, and with disease progression many clinical symptoms become worse with high probability of metastasis. Bone is the most common site of advanced metastasis of prostate cancer. Bone metastasis is a continuous and complex pathological process regulated by tumor cells and bone microenvironment, in which epithelial-mesenchymal transformation, homing and dormancy, reactivation, and proliferation of tumor cells are closely related to its occurrence and development. Several cytokines such as Receptor activator of NF-κB ligand (RANK-L) is overexpressed in bone microenvironment and prostate cancer. RANKL, chemokine family, and integrins are involved in bone metastasis of prostate cancer through complex interaction mechanisms. A variety of bone-targeting drugs such as bisphosphonates, RANKL inhibitors (denosumab) and radiotherapy drugs (radium-223, strontium-89, samarium-153), tyrosine kinase inhibitors, integrin-targeted drugs, etc. are approved for the prevention and treatment of skeletal related events caused by bone metastasis in prostate cancer patients. In this review, the biological mechanism of bone metastasis in prostate cancer and the research progress of bone-targeting drugs are reviewed.

CircRNA ITCH Inhibits Epithelial-Mesenchymal Transformation and Promotes Apoptosis in Papillary Thyroid Carcinoma via miR-106a-5p/JAZF1 Axis.

Circular RNA ITCH (circ-ITCH) is implicated in papillary thyroid carcinoma (PTC) development. Nevertheless, the more detailed molecular mechanism remains uncovered. The transcriptional level of circ-ITCH was tested via quantitative real-time PCR. Transwell assay was introduced to assess the migrative and invasive abilities of cells. RNA interference technology was employed to reduce the level of circ-ITCH as well as JAZF1 in PTC cells. Western blot assay was utilized to reveal the content of JAZF1 and proteins related to epithelial-mesenchymal transformation (EMT) progression. Circ-ITCH was downregulated in PTC tissues as well as cells. Overexpression of circ-ITCH suppressed EMT, migration, invasion, facilitated apoptosis in PTC cells, while silencing circ-ITCH exhibited reversed effects. Additionally, miR-106a-5p was the target of circ-ITCH and negatively regulated through circ-ITCH. MiR-106a-5p mimic partly eliminated the influences of overexpressed circ-ITCH in PTC cells. Moreover, JAZF1 could interact with miR-106a-5p, then it was regulated via circ-ITCH. Silencing JAZF1 partially counteracted the role of circ-ITCH in PTC cells progress. This study uncovered that circ-ITCH suppressed the development of PTC cells at least partly by mediating miR-106a-5p/JAZF1 network.

MICAL2 implies immunosuppressive features and acts as an independent and adverse prognostic biomarker in pancreatic cancer

At present, clinical outcomes of pancreatic cancer patients are still poor. New therapeutic targets for pancreatic cancer are urgently needed. Previous studies have indicated that Microtubule Associated Monooxygenase, Calponin and LIM Domain Containing 2 (MICAL2) is highly expressed in many tumors and promotes tumor progression. However, the role played by MICAL2 in pancreatic cancer remains unclear. Based on gene expression and clinical information from multiple datasets, we used comprehensive bioinformatics analysis in combination with tissue microarray to explore the function and clinical value of MICAL2. The results showed that MICAL2 was highly expressed in pancreatic cancer tissue and exhibited potential diagnostic capability. High expression of MICAL2 was also associated with poor prognosis and acted as an independent prognostic factor. MICAL2, mainly expressed in fibroblasts of pancreatic cancer, was closely related to metastasis and immune-related features, such as epithelial-mesenchymal transformation, extracellular cell matrix degradation, and inflammatory response. Furthermore, higher MICAL2 expression in pancreatic cancer was also associated with an increase in cancer-associated fibroblasts as well as M2 macrophage infiltration, and a reduction in CD8 + T cell infiltration, thereby facilitating the formation of an immunosuppressive microenvironment. Our results helped elucidate the clinical value and function in metastasis and immunity of MICAL2 in pancreatic cancer. These findings provided potential clinical strategies for diagnosis, targeted therapy combination immunotherapy, and prognosis in patients with pancreatic cancer.

Honokiol inhibits gallbladder cancer proliferation and epithelial mesenchymal transformation by suppressing TMPRSS4-induced PI3K/AKT activation

Purpose: To determine the role of TMPRSS4 in gallbladder cancer (GBC).&#x0D; Methods: Quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) and western blotting were used to evaluate the expression of genes, while CCK-8 kit and foci formation assay were used to assess cell growth in GBC-SD and non-obliterative zone (NOZ) cell lines. Cell apoptosis was evaluated by flow cytometry, while cell migration and cell invasion were determined by Transwell assay in GBCSD and NOZ cell lines.&#x0D; Results: TMPRSS4 was highly expressed in GBC cells, compared to normal cell, HIBEC. Overexpression of TMPRSS4 enhanced cell viability and 2D foci formation in GBC-SD (stratified) and NOZ; however, knockdown of TMPRSS4 reduced cell proliferation and colony formation in the cell lines (p &lt; 0.05). TMPRSS4 deficiency increased cell apoptosis but its reinforced expression decreased cell apoptosis in GBC cell lines (p &lt; 0.05). Moreover, TMPRSS4 positively regulated cell invasion and migration in GBC cells by upregulating TWIST1, vimentin and N- cadherin. TMPRSS4 also regulated the activation of PI3K/AKT signal pathway. Furthermore, honokiol inhibited gallbladder cancer proliferation and migration, and induced cell apoptosis by suppressing TMPRSS4-induced PI3K/AKT activation (p &lt; 0.05).&#x0D; Conclusion: TMPRSS4 plays an important role in regulating cell growth, apoptosis and metastasis of gallbladder cancer cells (GBC). Thus, TMPRSS4 might be a new biomarker in gallbladder cancer.

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.

Triptolide inhibits esophageal squamous cell carcinoma progression by regulating the circNOX4/miR-153-3p/SATB1 signaling pathway.

To explore the role and mechanism of triptolide in regulating esophageal squamous cell carcinoma (ESCC) progression by mediating the circular RNA (circRNA)-related pathway. The expression levels of circNOX4, miR-153-3p and special AT-rich sequence binding protein-1 (SATB1) were measured by qRT-PCR. Cell proliferation was confirmed by cell counting kit-8 assay and colony formation assay. Flow cytometry was employed to measure cell apoptosis and cell cycle process. Moreover, cell migration and invasion were detected using transwell assay. The protein levels of epithelial-mesenchymal transformation markers and SATB1 were determined by western blot analysis. Furthermore, dual-luciferase reporter assay and RIP assay were performed to confirm the interaction between miR-153-3p and circNOX4 or SATB1. Xenograft tumor models were built to verify the effects of triptolide and circNOX4 on ESCC tumor growth. CircNOX4 was highly expressed in ESCC tissues and cells, and its expression could be reduced by triptolide. Triptolide could inhibit ESCC proliferation, cell cycle process, migration, invasion, EMT process, and promote apoptosis, while these effects were reversed by circNOX4 overexpression. MiR-153-3p could be sponged by circNOX4, and the promotion effect of circNOX4 on the progression of triptolide-treated ESCC cells was abolished by miR-153-3p overexpression. SATB1 was a target of miR-153-3p. Also, SATB1 knockdown reversed the enhancing effect of miR-153-3p inhibitor on the progression of triptolide-treated ESCC cells. Triptolide reduced ESCC tumor growth by regulating the circNOX4/miR-153-3p/SATB1 axis. Triptolide could hinder ESCC progression, which was mainly achieved by regulating the circNOX4/miR-153-3p/SATB1 axis.

PTBP1 promotes the progression of hepatocellular carcinoma by enhancing the oncogenic splicing switch of FGFR2.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer accounting for 90% of cases. It is a highly invasive and deadly cancer with a gradual onset. Polypyrimidine tract-binding protein 1 (PTBP1) is an important RNA-binding protein involved in RNA metabolism and has been linked to oncogenic splicing events. While the oncogenic role of PTBP1 in HCC cells has been established, the exact mechanism of action remains unclear. This study aimed to investigate the functional connection between PTBP1 and dysregulated splicing events in HCC. Through immunoprecipitation-mass spectrometry analyses, we discovered that the proteins bound to PTBP1 were significantly enriched in the complex responsible for the alternative splicing of FGFR2 (fibroblast growth factor receptor 2). Further RNA immunoprecipitation and quantitative PCR assays confirmed that PTBP1 down-regulated the FGFR2-IIIb isoform levels and up-regulated the FGFR2-IIIc isoform levels in HCC cells, leading to a switch from FGFR2-IIIb to FGFR2-IIIc isoforms. Subsequent functional evaluations using CCK-8, transwell, and plate clone formation assays in HCC cell lines HepG2 and Huh7 demonstrated that FGFR2-IIIb exhibited tumor-suppressive effects, while FGFR2-IIIc displayed tumor-promoting effects. In conclusion, this study provides insights into the PTBP1-mediated alternative splicing mechanism in HCC progression, offering a new theoretical basis for the prevention and treatment of this malignancy. Mechanistically, the isoform switch from FGFR2-IIIb to FGFR2-IIIc promoted epithelial-mesenchymal transformation (EMT) of HCC cells and activated the FGFR cascades ERK and AKT pathways.

IKBKE promotes the ZEB2-mediated EMT process by phosphorylating HMGA1a in glioblastoma

IKBKE (Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Epsilon) is an important oncogenic protein in a variety of tumors, which can promote tumor growth, proliferation, invasion and drug resistance, and plays a critical regulatory role in the occurrence and progression of malignant tumors. HMGA1a (High Mobility Group AT-hook 1a) functions as a cofactor for proper transcriptional regulation and is highly expressed in multiple types of tumors. ZEB2 (Zinc finger E-box Binding homeobox 2) exerts active functions in epithelial mesenchymal transformation (EMT). In our current study, we confirmed that IKBKE can increase the proliferation, invasion and migration of glioblastoma cells. We then found that IKBKE can phosphorylate HMGA1a at Ser 36 and/or Ser 44 sites and inhibit the degradation process of HMGA1a, and regulate the nuclear translocation of HMGA1a. Crucially, we observed that HMGA1a can regulate ZEB2 gene expression by interacting with ZEB2 promoter region. Hence, HMGA1a was found to promote the ZEB2-related metastasis. Consequently, we demonstrated that IKBKE can exert its oncogenic functions via the IKBKE/HMGA1a/ZEB2 signalling axis, and IKBKE may be a prominent biomarker for the treatment of glioblastoma in the future.

Characterization and verification of CAF-relevant prognostic gene signature to aid therapy in bladder cancer

Cancer-associated fibroblasts (CAFs) are significantly involved in determining the patient's prognosis and response to bladder cancer (BLCA) therapy. CAFs can induce epithelial-mesenchymal transformation (EMT) as well as complex interaction with immune cells. Hence, it is imperative to identify potential markers for enhancing our understanding of CAFs in BLCA progression and immune regulation. A variety of algorithms and analyses were employed in the study, leading to the development of a novel prognostic feature for CAFs-Stromal-EMT (CSE)-prognostic feature. This feature was constructed based on the genes MFAP5, PCOLCE2, and JUN. Furthermore, we revealed that patients with higher CSE risk scores responded to immunotherapy better compared to those with lower. Finally, we verified two CSE-related genes using in vitro experiments. Our results suggested that the CSE-prognostic feature could predict the prognosis and evaluate the response of patients to immune and chemotherapies. This would aid clinicians in designing treatment strategies for patients with BLCA.

FOXD1 promotes proliferation, migration, and epithelial-mesenchymal transformation in esophageal squamous cell carcinoma by targeting SNAI1

The transcription factor Forkhead box D1 (FOXD1) is a crucial member of the FOX family and is widely expressed in human embryonic cells, where it plays a regulatory role in organogenesis. However, the precise functions and molecular mechanisms of FOXD1 in esophageal squamous cell carcinoma (ESCC) are not fully clarified. This study aimed to analyze the expression of FOXD1 in ESCC, investigate its relationship with clinicopathological features and prognosis, and elucidate its role in ESCC tumorigenesis and progression. We found a significant up-regulation of FOXD1 mRNA and protein expression in ESCC (p < 0.01), which exhibited a negative correlation with prognosis. Notably, the expression level of FOXD1, along with tumor TNM stage and lymph node metastasis, emerged as independent prognostic factors for ESCC patients (p < 0.01). In addition, we observed that FOXD1 promoted ESCC cell proliferation, migration, and invasion in vitro. Furthermore, we identified a positive correlation between FOXD1 and SNAI1 in ESCC. Through direct binding to the SNAI1 promoter, FOXD1 enhanced its transcriptional activity, thereby regulating the epithelial-mesenchymal transition (EMT) process and activating TGF-β signaling. These findings suggested that FOXD1 may function as a tumor activator and represent a potential novel therapeutic target for ESCC.

The Antimicrobial Peptide Merecidin Inhibit the Metastasis of Triple-Negative Breast Cancer by Obstructing EMT via miR-30d-5p/Vimentin.

Purpose: To investigate the inhibitory effect of antimicrobial peptide merecidin on triple-negative breast cancer (TNBC) and the mechanism of inhibiting epithelial-mesenchymal transformation (EMT) by regulating miR-30d-5p/vimentin. Methods: TNBC cell lines (MDA-MB-231, MDA-MB-468) were treated with merecidin to assess proliferation, migration, invasion ability, and EMT. Confocal laser localization was used to examine the role of merecidin and TNBC cells. The relationship between merecidin and miR-30d-5p was determined through RT-qPCR and dual-luciferase reporter gene, and the relationship between merecidin and vimentin was verified through pulling down the experiment. The effects of miR-30d-5p on the migration and invasion ability of TNBC cells were confirmed through scratch and transwell experiments. Vimentin levels, tumor volume, shape, size, and weight were observed in the MDA-MB-231 subcutaneous tumor model in nude mice. Results: merecidin inhibited the proliferation, migration, invasion, and EMT of TNBC cells. merecidin was primarily located in the cytoplasm of TNBC cells, and the expression of miR-30d-5p was low in TNBC cells. merecidin significantly up-regulated the expression of miR-30d-5p. miR-30d-5p negatively regulated vimentin. merecidin could bind to vimentin in vitro. miR-30d-5p inhibited the migration and invasion ability of TNBC cells, while vimentin promoted their migration and invasion ability. Down-regulation of miR-30d-5p or overexpression of vimentin partially counteracted the inhibitory effects of merecidin on TNBC cell migration, invasion ability, and EMT. In nude mouse tumor models, merecidin significantly suppressed tumor growth. Conclusion: Merecidin effectively blocks the EMT process and inhibits the migration and invasion of TNBC cells by regulating miR-30d-5p/vimentin.