MBD3 promotes epithelial-mesenchymal transition in gastric cancer cells by upregulating ACTG1 via the PI3K/AKT pathway.

BACKGROUND: Gastric cancer (GC) is a common malignancy and a leading cause of cancer-related death with high morbidity and mortality. Methyl-CpG binding domain protein 3 (MBD3), a key epigenetic regulator, is abnormally expressed in several cancers, participating in progression and metastasis. However, the role of MBD3 in GC remains unknown. METHODS: MBD3 expression was assessed via public databases and validated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The prognosis of MBD3 was analysed via bioinformatics based on the TCGA dataset. The migration, invasion and proliferation of GC cells were examined by transwell, wound healing, cell counting kit (CCK)-8, colony-formation and xenograft mouse models. Epithelial-mesenchymal transition (EMT) and phosphatidylinositide 3-kinases/ protein Kinase B (PI3K/AKT) pathway markers were evaluated by Western blotting. RNA sequencing was used to identify the target of MBD3. RESULTS: MBD3 expression was higher in GC tissues and cells than in normal tissues and cells. Additionally, high MBD3 levels were associated with poor prognosis in GC patients. Subsequently, we proved that MBD3 enhanced the migration, invasion and proliferation abilities of GC cells. Moreover, western blot results showed that MBD3 promoted EMT and activated the PI3K/AKT pathway. RNA sequencing analysis showed that MBD3 may increase actin γ1 (ACTG1) expression to promote migration and proliferation in GC cells. CONCLUSION: MBD3 promoted migration, invasion, proliferation and EMT by upregulating ACTG1 via PI3K/AKT signaling activation in GC cells and may be a potential diagnostic and prognostic target.

LncRNA UCA1 promotes pancreatic cancer cell migration by regulating mitochondrial dynamics via the MAPK pathway.

PURPOSE: Long non-coding RNA urothelial cancer associated 1 (UCA1) serves as an oncogene in various cancers. However, the mechanism underlying the role of UCA1 in pancreatic cancer remains unclear. This study aimed to explore the role of UCA1 in pancreatic cancer. METHODS: The expression and prognosis of UCA1 were analyzed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The results were validated by immunohistochemistry (IHC) and qRT-PCR. The biofunctions of UCA1 were analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The migration abilities and mitochondrial dynamics of PC cells were examined using the Transwell assay, mitochondrial membrane potential (MMP), and fluorescence. The mitochondrial-related protein and MAPK/ERK pathway markers were evaluated using western blotting. RESULTS: UCA1 expression was significantly higher in pancreatic cancer tissues than in normal tissues. High UCA1 expression indicated poor clinical outcomes and was associated with clinical features in patients with pancreatic cancer. Additionally, high UCA1 expression is a potential independent marker for poor prognosis. Subsequently, we demonstrated that UCA1 enhanced the migration capability, increased MMP, enhanced mitochondrial fusion, and inhibited mitochondrial autophagy in pancreatic cancer cells via the MAPK/ERK pathway. CONCLUSION: UCA1 promotes the migration by regulating the mitochondrial dynamics of pancreatic cancer cells via the MAPK/ERK pathway. Our findings suggest that UCA1 may serve as a potential biomarker in pancreatic cancer prognosis.

Pan-Cancer Analysis Reveals SOX2 as a Promising Prognostic and Immunotherapeutic Biomarker Across Various Cancer Types, Including Pancreatic Cancer.

SOX2 is associated with the initiation, growth, and progression of various tumors and is related to stem cells. However, further studies of SOX2 in a pan-cancer context are warranted. In this study, we obtained pan-cancer and clinical data from TCGA, GTEx, STRING, and TISIDB databases and we analyzed the relationship between SOX2 expression levels and changes in gene diagnostics and survival prognosis. Additionally, we compared the expression levels of SOX2 in pancreatic cancer and healthy pancreatic tissues using Wilcoxon's rank-sum test. Functional enrichment analysis was conducted to identify potential signaling pathways and biological functions. To determine the prognostic value, we used the area under the curve (AUC) and Cox regression analysis. We further developed nomograms to predict overall survival at 1, 6, and 12 months after cancer diagnosis. Moreover, we assessed immune cell infiltration using single-sample gene set enrichment analysis. The methylation status of SOX2 was analyzed using the UALCAN and MethSurv databases. Furthermore, we verified the differential expression of SOX2 in pancreatic cancer cell lines by western blotting and quantitative polymerase chain reaction. We also confirmed the effect of SOX2 on the invasion and migration of pancreatic cancer cells using transwell and scratch assays. The biological effects were confirmed using a clone-formation assay. Our findings suggest that SOX2 is highly expressed in various tumor tissues and has potential clinical significance. It can be used as a new biomarker for pancreatic adenocarcinoma and plays a crucial role in immune infiltration.

Hypoxia-elicited Exosomes Promote the Chemoresistance of Pancreatic Cancer Cells by Transferring LncROR via Hippo Signaling.

Recent studies have found that hypoxia contributes to tumor progression and drug resistance by inducing the secretion of exosomes. However, the mechanism underlying this resistance in pancreatic cancer remains to be explored. In this study, we investigated the effect of hypoxia-induced tumor-derived exosomes (Hexo) on stemness and resistance to gemcitabine in pancreatic cancer cells, as well as the molecular mechanisms involved in this process. Firstly, we discovered that hypoxia promoted stemness and induced resistance to gemcitabine in pancreatic cancer cells. Secondly, we showed that exosomes secreted by pancreatic cancer cells under normoxic or hypoxic conditions can be transfected into tumor cells. Thirdly, it was demonstrated that Hexo promotes proliferation, stemness, and resistance to gemcitabine in pancreatic cancer cells, as well as inhibits the apoptosis and cell cycle arrest induced by gemcitabine. Finally, it was verified that Hexo inactivated the Hippo/Yes-associated protein (Hippo/YAP) pathway in pancreatic cancer cells by transferring exosomal long non-coding RNA regulator of reprogramming (lncROR). In summary, the hypoxic tumor microenvironment could promote stemness and induce resistance to gemcitabine in pancreatic cancer cells. Mechanistically, Hexo enhanced stemness to promote chemoresistance in pancreatic cancer cells by transferring lncROR via Hippo signaling. Thus, exosomal lncROR may serve as a candidate target of chemotherapy for pancreatic cancer.

LncRNA FAM83A-AS1 promotes epithelial-mesenchymal transition of pancreatic cancer cells via Hippo pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been proved to play a vital role in pancreatic cancer (PC). However, the role of lncRNA FAM83A-AS1 in PC remains unclear. In this study, we explored the biological function and underlying mechanism of FAM83A-AS1 in PC cells. METHODS: The FAM83A-AS1 expression was assessed via public databases and validated by qRT-PCR. The biofunction and immune cell infiltration of FAM83A-AS1 were analyzed through GO, KEGG, GESA and ssGSEA. The migration, invasion and proliferation abilities of PC cells were examined by Transwell, wound healing, CCK8 and colony formation. The EMT and Hippo pathway markers were evaluated by western blot. RESULTS: FAM83A-AS1 expression was higher in PC tissues and cells than normal. Additionally, FAM83A-AS1 was associated with poor prognosis of PC and involved in cadherin binding and immune infiltration. Subsequently, we proved FAM83A-AS1 overexpression enhanced the migration, invasion and proliferation abilities of PC cells, whereas FAM83A-AS1 downregulation inhibited those. Moreover, western blot results showed that FAM83A-AS1 knockdown increased the E-cadherin expression and decreased the expression of N-cadherin, ß-catenin, Vimentin, Snail and Slug. On the contrary, FAM83A-AS1 upregulation results in the opposite effects. Besides, FAM83A-AS1 overexpression inhibited the expression of p-YAP, p-MOB1, p-Lats1, SAV1, MST1 and MST2 as well as the results of FAM83A-AS1 knockdown were opposite. CONCLUSION: FAM83A-AS1 promoted EMT of PC cells via Hippo signaling inactivation and may be a potential diagnosis and prognosis target.

CTSK and PLAU as Prognostic Biomarker and Related to Immune Infiltration in Pancreatic Cancer: Evidence from Bioinformatics Analysis and qPCR.

Pancreatic adenocarcinoma (PAAD) is a malignancy with the highest mortality rate worldwide. There is a pressing need for novel biomarkers that can facilitate early detection and serve as targets for therapeutic interventions beyond the commonly utilized CA199 marker. This study utilized microarray datasets (GSE15471, GSE62165, and GSE28735) from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) and construct a protein-protein interaction network using STRING and Cytoscape. Hub genes were selected using BiNGO. Expression profiles and clinical data from the Cancer Genome Atlas (TCGA) were then used to compare the expression levels of CTSK and PLAU in pancreatic cancer and healthy pancreatic tissues via the Wilcoxon rank-sum test, with further validation using qPCR. Functional enrichment analysis was conducted to explore potential signaling pathways and biological functions. Prognostic values were assessed by the Kaplan-Meier and Cox regression analyses, and an overall survival (OS) nomogram was created to predict 1-, 2-, and 3-year survival after cancer diagnosis. The infiltration of immune cells was evaluated by single-sample gene set enrichment analysis. The methylation status of both genes was analyzed using the UALCAN and MethSurv databases. The results demonstrated that CTSK and PLAU were overexpressed in pancreatic cancer and that the hypomethylation status of both genes was associated with a poor prognosis. The overexpression of both genes was positively correlated with various immune cells, and functional enrichment analysis revealed that they were associated with immune cell infiltration. Besides, the effects of PLAU on the migration and invasion of pancreatic cancer cells were also verified by scratch and transwell experiments. Consequently, CTSK and PLAU have potential as prognostic biomarkers for pancreatic cancer.

A metamaterial ultrasound mode convertor for complete transformation of Lamb waves into shear horizontal waves.

This article reports a new mechanism involving a non-perforated resonant elastic metamaterial to achieve the complete conversion of Lamb waves (A0 and S0) into the fundamental shear horizontal (SH0) wave. The proposed metamaterial ultrasound mode convertor is studied via the observation of the special resonant shear motion of its unit cells, initiating with a conventional additive stub design. Thereafter, such a stubbed structure is further modified to fully couple the Lamb modes with the shear horizontal stub motion. By investigating the band structure of the metamaterial unit cell through modal analysis and tuning the shear resonant motions, a complete SH0 mode generation band within the simultaneous Lamb modes bandgap can be established in a wide frequency range. Such a special bandgap situation enables the complete mode conversion from Lamb waves into shear horizontal waves. The transformation capability of the proposed ultrasound mode convertor is further substantiated via the harmonic analysis of metamaterial chain model, showcasing the frequency spectrum of the transmitted wave modes. The optimal configuration is determined by conducting a parametric study to identify the most effective mode conversion performance. Finally, a coupled-field transient finite element simulation is carried out to acquire the dynamic response of the structure. The frequency-wavenumber analysis of the transmitted wave field illuminates the successful realization of the mode conversion behavior. Experimental demonstrations are presented to validate the numerical predictions. The proposed complete mode conversion capability may possess great potential for wave control and manipulation.

Observation of two-dimensional Faraday waves in extremely shallow depth.

A family of two-dimensional Faraday waves in extremely shallow depth (1 mm to 2 mm) of absolute ethanol are observed experimentally using a Hele-Shaw cell that vibrates vertically. The same phenomena are not observed by means of water, ethanol solution, and silicone oil. These Faraday waves are quite different from the traditional ones. These phenomena are helpful to deepen and enrich our understandings about Faraday waves, and besides provide a challenging problem for computational fluid dynamics.