Epithelial-mesenchymal Transition In Gastric Cancer Research Articles

Retraction Note: MicroRNA-93-5p promotes epithelial-mesenchymal transition in gastric cancer by repressing tumor suppressor AHNAK expression

Retraction Note: MicroRNA-93-5p promotes epithelial-mesenchymal transition in gastric cancer by repressing tumor suppressor AHNAK expression

Enhanced epithelial-mesenchymal transition signatures are linked with adverse tumor microenvironment, angiogenesis and worse survival in gastric cancer.

Epithelial-mesenchymal transition (EMT) is a crucial mechanism that facilitates cancer cell metastasis. Despite its importance, the clinical significance of EMT in gastric cancer (GC) patients has yet to be clearly demonstrated. For gauging the extent of EMT in GC, we employed gene set variation analysis to score 807 patient samples from two large cohorts: TCGA and GSE84437. In both cohorts, EMT high GC showed a significant association with worse overall survival (hazard ratio (HR) = 1.74, p = 0.011 and HR = 2.01, p < 0.001, respectively). This association was stronger when considering the EMT signature score compared to the individual expressions of EMT-related genes (CDH1, CDH2, VIM, and FN1). While the EMT signature level did not differ among various cancers, high EMT signature specifically correlated with survival in GC alone. Mucinous and diffuse histological types exhibited higher EMT levels compared to others (p < 0.001), and the EMT signature level was correlated with tumor depth and AJCC stage (all p < 0.001). Interestingly, the EMT score was an independent factor for overall and disease-specific survival (multivariate; p = 0.006 and 0.032, respectively). EMT high GC displayed a lower fraction of Th1 cells and a higher fraction of dendritic cells, M1 macrophages and several stromal cells. EMT high GC exhibited an inverse correlation with cell proliferation-related gene sets. While they significantly enriched multiple pro-cancerous gene sets, such as TGF-β signaling, hypoxia, and angiogenesis. The presence of EMT signature in a bulk tumor was linked to TGF-β signaling, hypoxia, and angiogenesis, and was also associated with poorer survival outcomes in GC patients.

DEC1 is involved in TGF-β1-induced epithelial-mesenchymal transition of gastric cancer

DEC1 is involved in TGF-β1-induced epithelial-mesenchymal transition of gastric cancer

LncRNA MIR200CHG inhibits EMT in gastric cancer by stabilizing miR-200c from target-directed miRNA degradation

Gastric cancer (GC) is a heterogeneous disease, threatening millions of lives worldwide, yet the functional roles of long non-coding RNAs (lncRNAs) in different GC subtypes remain poorly characterized. Microsatellite stable (MSS)/epithelial-mesenchymal transition (EMT) GC is the most aggressive subtype associated with a poor prognosis. Here, we apply integrated network analysis to uncover lncRNA heterogeneity between GC subtypes, and identify MIR200CHG as a master regulator mediating EMT specifically in MSS/EMT GC. The expression of MIR200CHG is silenced in MSS/EMT GC by promoter hypermethylation, associated with poor prognosis. MIR200CHG reverses the mesenchymal identity of GC cells in vitro and inhibits metastasis in vivo. Mechanistically, MIR200CHG not only facilitates the biogenesis of its intronic miRNAs miR-200c and miR-141, but also protects miR-200c from target-directed miRNA degradation (TDMD) through direct binding to miR-200c. Our studies reveal a landscape of a subtype-specific lncRNA regulatory network, providing clinically relevant biological insights towards MSS/EMT GC.

An aptamer and Au/Si CCA based SERS sensor for ultra-sensitive detection of Vimentin during EMT in gastric cancer.

Introduction: In this study, a surface-enhanced Raman scattering (SERS) sensor based on a functionalized Au/Si cap-cone array (Au/Si CCA) was constructed using the identity-release strategy to detect Vimentin changes during epithelial-mesenchymal transition (EMT) in gastric cancer (GC). Methods: The periodic structure of Au/Si CCA, which can form "hot spots" with high density and regular arrangement, is a substrate with excellent performance. Au/Si CCA was functionalized with aptamers as the capture substrate, and Au nanocubes (AuNCs) were modified with 5-carboxyfluorescein (5-FAM) labelled complementary strand as SERS probe. The capture substrate and SERS probe were assembled by hybridization, and the SERS signal intensity of 5-FAM was greatly enhanced. The binding of Vimentin to the aptamer resulted in a broken connection between the SERS sensor Au/Si CCA array and AuNCs, which resulted in a decrease in the signal intensity of 5-FAM. The identity-release strategy requires only a simple step of reaction to achieve rapid detection of target proteins, which has clinical practicability. Results: Using this protocol, the concentration of Vimentin in GES-1 cells could be successfully detected, and the detection limit was as low as 4.92pg/mL. Biological experiments of Vincristine, Oncovin (VCR)-treated GES-1 cells effectively mimicked the EMT process, and Vimentin changes during EMT could be accurately detected by this method. Discussion: This study provides a selective, ultra-sensitive and accurate assay for Vimentin detection, which may provide a means for the future detection of EMT process in GC.

High-Mobility Group Box 1 Overexpression Predicts a Poor Prognosis and Promotes Epithelial-Mesenchymal Transition in Gastric Cancer by Activating TLR4/NF-κB Signaling

Introduction: The molecular mechanism of high-mobility group box 1 (HMGB1) promoting the epithelial-mesenchymal transition (EMT) of gastric cancer (GC) has not been known well. This study aimed to explore the clinical effects of HMGB1 expression levels on the clinicopathological characteristics of patients with GC and to uncover the potential molecular mechanism which promotes tumor progression. Methods: The expression levels of HMGB1 in 125 patients with GC were detected by immunohistochemistry and Western blotting. Univariate and multivariate analyses were performed to evaluate the relationship between HMGB1 expression and clinical characteristics of patients with GC. Stable overexpression (over-HMGB1) and knockdown (sh-HMGB1) GC cell lines (AGS and MKN-45) were used to determine the effects of HMGB1 on the activation of TLR4/NF-κB signaling. Differences were considered statistically significant at p Results: HMGB1 is highly expressed in GC tissues and cell lines. High HMGB1 expression (HR = 1.89, 95% CI: 1.44–2.39, p = 0.001) was an independent risk factor for overall survival in patients with GC. Downregulation of HMGB1 resulted in downregulation of TLR4 and NF-κB subunit (p-p65 and p-IκBα) expression, whereas the upregulated expression of HMGB1 led to increased expression of TLR4 and NF-κB subunits. Overexpression of HMGB1 promotes the upregulation of EMT-TF expression, which enhances the proliferation and migration abilities of GC cell lines. Conclusion: HMGB1 is highly expressed in GC tissues and is associated with a poorer prognosis in patients with GC. HMGB1 activates the TLR4/NF-κB signaling pathway to promote EMT progression in GC cell lines. HMGB1 may be a critical molecule in prognosis prediction and a therapeutic target for patients with GC.

LncRNA THUMPD3-AS1 promotes invasion and EMT in gastric cancer by regulating the miR-1297/BCAT1 pathway

Long noncoding RNA (lncRNA) plays crucial roles in the development of gastric cancer (GC); however, studies of their mechanisms of action are needed to determine their clinical value. The aim of this study is to explore the effects and mechanisms of THUMPD3-AS1 in GC. Elevated levels of THUMPD3-AS1 were observed in GC and demonstrated a significant positive correlation with poor prognosis. Functionally, THUMPD3-AS1 promoted GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and induced tumor growth invivo. THUMPD3-AS1 exerts its regulatory function on BCAT1 through competitive binding with miR-1297. Further investigations confirmed that both THUMPD3-AS1 and miR-1297 interact with BCAT1. These findings suggest that THUMPD3-AS1 promotes GC invasion and EMT by regulating the miR-1297/BCAT1 pathway, indicating that THUMPD3-AS1 may serve as a biomarker and therapeutic target for GC.

Association of enhanced epithelial-mesenchymal transition signature with tumor microenvironment, angiogenesis, and survival in gastric cancer.

e16002 Background: Among the hallmarks of cancer, epithelial-mesenchymal transition (EMT) that epithelial cancer cells gain the characteristics of mesenchymal cells, is one of the key mechanisms of cancer cell metastasis. On the other hand, the clinical relevance of EMT that occurs in gastric cancer patients has not been clearly shown. Methods: To measure the level of EMT in gastric cancer, gene set variation analysis was used to score total of 807 gastric cancer patient samples from two independent large cohorts; TCGA and GSE84437. Results: EMT high gastric cancer was significantly associated with worse overall survival (hazard ratio (HR)=1.74, p=0.011 in the TCGA, and HR=2.01, p&lt;0.001 in the GSE84437), and the association was stronger with EMT signature score compared to expressions of each EMT-related genes, CDH1, CDH2, VIM, or FN1. EMT signature levels were not significantly different among gastric cancer, hepatocellular carcinoma, colorectal cancer, breast cancer, and pancreatic ductal adenocarcinoma, and high level of EMT signature was associated with survival only in gastric cancer. Among the histological types, mucinous and diffuse type had high EMT level compared to tubular, papillary, or signet gastric cancer ( p&lt;0.001). EMT signature level was significantly correlated with tumor depth and AJCC stage (all p&lt;0.001), but not consistently with lymphatic metastasis. Interestingly, the EMT score was independent factor for patient survival including clinicopathological features, not only for overall survival but also disease-specific survival in the TCGA cohort (multivariate; p=0.006 and 0.032, respectively). EMT high gastric cancer was associated with low fraction of Th1 cells and high fraction of dendritic cells and M1 macrophages (all p&lt;0.001 in both cohort), but not with interferon-gamma immune response. EMT high gastric cancer tended to be inversely correlated with cell proliferation-related gene sets, and significantly associated with high infiltration fraction of stromal cells, including fibroblasts, adipocytes (all p&lt;0.001). On the other hand, they significantly enriched multiple pro-cancerous gene sets, such as TGF-β signaling, hypoxia, and angiogenesis, consistent with infiltration of angiogenesis-related stromal cells such as microvascular and lymphatic endothelial cells, and pericytes (all p&lt;0.001). These results were shown consistently in two large cohort; TCGA and GSE84437. Conclusions: EMT signature in a bulk tumor was associated with cancer aggravating pathways such as TGF-β signaling, hypoxia, and angiogenesis, as well as with worse survival in gastric cancer patients.

Solasodine suppresses the metastasis of gastric cancer through claudin-2 via the AMPK/STAT3/NF-κB pathway

Gastric cancer (GC) is one of the most common malignancies, and it has become the third most common malignant tumour in the world. Targeting metastasis has also become a key and difficult point in the treatment of GC. Solasodine is an active ingredient isolated from Solanum nigrum L. for the treatment of various cancers, such as breast cancer, pancreatic cancer and lung cancer. In the present study, we investigated the role and mechanism of solasodine in inhibiting GC. In vitro, we found that solasodine not only promoted cell death but also inhibited the migration and invasion of HGC27 and AGS cells. Solasodine regulated epithelial-mesenchymal transition (EMT) and reduced the expression of claudin-2 (CLDN2). Moreover, overexpression of CLDN2 inhibited the prometastatic phenotype and EMT of GC, and solasodine recovered this phenotype. Furthermore, the knockdown of CLDN2 had the opposite effect. We also found that the AMPK activators metformin and AICAR activated phosphorylation of AMPK and downregulated the expression of RhoA and CLDN2, indicating that AMPK was the upstream regulator of CLDN2. Solasodine could also activate AMP-activated protein kinase (AMPK) and inhibit the phosphorylation of STAT3 and the nuclear translocation of NF-κB. Therefore, solasodine may have prevented EMT by modulating the AMPK/STAT3/NF-κB/CLDN2 signalling pathway. In vivo, we established a xenograft model to investigate the phosphorylation of AMPK and the expression of CLDN2 from tumour tissues, and we found that solasodine inhibited tumour growth through AMPK-CLDN2 pathway. To sum up, solasodine prevented EMT by modulating the AMPK/STAT3/NF-κB/CLDN2 signalling pathway, becoming a new solution for inhibiting GC metastasis.

Bone mesenchymal stem cells promote gastric cancer progression through TGF-β1/Smad2 positive feedback loop

AimsBone marrow-derived mesenchymal stem cells (BMSCs) have been proven to be recruited into the tumor microenvironment and contribute to gastric cancer (GC) progression, but the underlying mechanism is still unclear. The purpose of this study is to explore the exact role and potential mechanism of BMSCs in the progression of GC. Materials and methodsBioinformatics analyzed were used to clarify the correlation between TGF-β1 and prognosis of gastric cancer. Cell co-culture were used to explore the interaction between gastric cancer cells (GCs) and BMSCs. Quantitative real time-PCR and Western blot assay were used to detect gene and protein expression, respectively. The biological characteristics of GCs and BMSCs were detected by immunofluorescence, Transwell migration, Elisa and invasion assay. Xenograft models in nude mice were constructed to evaluate GC development in vivo. Key findingsTGF-β1 was overexpressed in GC cells and tissues, and is positively related to the poor prognosis of patients. TGF-β1 from GCs activated the Smad2 pathway in BMSCs, promoting their differentiation into carcinoma-associated fibroblasts (CAFs) and TGF-β1 expression. Concomitantly, TGF-β1 secreted by CAFs activate Smad2 signaling in GC cells, thus inducing their epithelial-mesenchymal transition (EMT) and TGF-β1 secretion. BMSCs can dramatically promote the proliferation, migration, and invasion of GCs while blocking TGF-β1/Smad2 positive feedback loop can reverse these effects. SignificanceThe TGF-β1/Smad2 positive feedback loop between GCs and BMSCs, promotes the CAFs differentiation of BMSCs and the EMT of GCs, resulting in the progression of GC.

Helicobacter pylori promotes epithelial-to-mesenchymal transition by downregulating CK2β in gastric cancer cells

Strains of Helicobacter pylori that are positive for the oncoprotein CagA (cytotoxin-associated gene A) are associated with gastric cancer and might be related to the epithelial-to-mesenchymal transition (EMT). Casein kinase 2 (CK2) is a serine/threonine protein kinase that plays a major role in tumorigenesis through signaling pathways related to the EMT. However, the role played by the interaction between CagA and CK2 in gastric carcinogenesis is poorly understood. Although CK2α protein expression remained unchanged during H. pylori infection, we found that CK2α kinase activity was increased in gastric epithelial cells. We also found that the CK2β protein level decreased in H. pylori-infected gastric cancer cells in CagA-dependent manner and demonstrated that CagA induced CK2β degradation via HDM2 (human double minute 2; its murine equivalent is MDM2). We observed that CagA induced HDM2 protein phosphorylation and that p53 levels were decreased in H. pylori-infected gastric cancer cells. In addition, downregulation of CK2β induced AKT Ser473 phosphorylation and decreased the AKT Ser129 phosphorylation level in gastric cancer cells. We also found that the downregulation of CK2β triggered the upregulation of Snail levels in gastric cancer cells. Furthermore, our in vivo experiments and functional assays of migration and colony formation suggest that CK2β downregulation is a major factor responsible for the EMT in gastric cancer. Therefore, CK2 could be a key mediator of the EMT in H. pylori-infected gastric cancer and could serve as a molecular target for gastric cancer treatment.

Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells.

BACKGROUNDInterleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated.AIMTo investigate whether and how IL-34 affects the proliferation of GC cells and EMT.METHODSUsing immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting.RESULTSExpression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice.CONCLUSIONIL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.

Flotillin-1 promotes EMT of gastric cancer via stabilizing Snail.

Gastric cancer is one of the most common malignancies worldwide and has been identified as the third leading cause of cancer-related mortality. Flotillin-1 is a lipid raft-associated scaffolding protein and plays an important role in the progression and development of several malignant carcinomas. Flotillin-1 is involved in epithelial-mesenchymal transition (EMT) process of several solid tumors to promote metastasis. However, the detailed characteristics and mechanisms of Flotillin-1 in gastric cancer have rarely been investigated. In this study, we found Flotillin-1 upregulated in gastric cancer, and the high expression of Flotillin-1 correlated with a worse prognosis. The migration and invasion ability of gastric cancer cells was upregulated by overexpressing Flotillin-1. Knockdown of Flotillin-1 inhibits gastric cancer cells metastasis. Flotillin-1 is a key regulator of EMT process and promotes gastric cancer cells metastasis through inducing EMT. Flotillin-1 may interact with a deubiquitinase to inhibit the ubiquitination of Snail in gastric cancer cells to promote EMT process. Our study provides a rationale and potential target for the treatment of gastric cancer.

MiR-192-5p/RB1/NF-κBp65 signaling axis promotes IL-10 secretion during gastric cancer EMT to induce Treg cell differentiation in the tumour microenvironment.

BackgroundRegulatory T (Treg) cells are important components of the tumour microenvironment (TME) that play roles in gastric cancer (GC) metastasis. Although tumour cells that undergo epithelial‐mesenchymal transition (EMT) regulate Treg cell function, their regulatory mechanism in GC remains unclear.MethodsThe miR‐192‐5p was identified by examining three Gene Expression Omnibus GC miRNA expression datasets. RNA immunoprecipitation (RIP) and dual‐luciferase reporter assays were conducted to identify interactions between miR‐192‐5p and RB1. The role of miR‐192‐5p/RB1 in GC progression was evaluated based on EdU incorporation, wound healing and Transwell assays. An in vitro co‐culture assay was performed to measure the effect of miR‐192‐5p/RB1 on Treg cell differentiation. In vivo experiments were conducted to explore the role of miR‐192‐5p in GC progression and Treg cell differentiation.ResultsMiR‐192‐5p was overexpressed in tumour and was associated with poor prognosis in GC. MiR‐192‐5p bound to the RB1 3′‐untranslated region, resulting in GC EMT, proliferation, migration and invasion. MiR‐192‐5p/RB1 mediated interleukin‐10 (IL‐10) secretion by regulating nuclear factor‐kappaBp65 (NF‐κBp65), affecting Treg cell differentiation. NF‐κBp65, in turn, promoted miR‐192‐5p expression and formed a positive feedback loop. Furthermore, in vivo experiments confirmed that miR‐192‐5p/RB1 promotes GC growth and Treg cell differentiation.ConclusionCollectively, our studies indicate that miR‐192‐5p/RB1 promotes EMT of tumour cells, and the miR‐192‐5p/RB1/NF‐κBp65 signaling axis induces Treg cell differentiation by regulating IL‐10 secretion in GC. Our results suggest that targeting miR‐192‐5p/RB1/NF‐κBp65 /IL‐10 may pave the way for the development of new immune treatments for GC.

LncRNA DLEU2 silencing impedes the migration, invasion and EMT in gastric cancer cell by suppressing PI3K/AKT signaling pathway

Context: The high expression of long non-coding RNA deleted in lymphocytic leukaemia 2 (lncRNA DLEU2) has been confirmed in gastric cancer (GC). Objective: However, the detailed mechanism concerning its involvement in GC remained unclear, which we aimed to explore in this study. Materials and methods: LncRNA DLEU2 expression in GC was estimated by bioinformatic analysis, and the relationship between the expression of DLEU2 and the clinicopathological characteristics of patients with GC was performed. qRT-PCR was employed to detect the expression of lncRNA DLEU2 and confirm the transfection efficiency following the knockdown or overexpression of DLEU2. Functional assays, including CCK-8, flow cytometry, scratching test and Transwell assays, were used to determine the role of DLEU2 in tumor phenotypes. The effects of DLEU2 on the PI3K/Akt pathway were detected by western blot. For elucidating the functions of DLEU2/PI3K/Akt axis in GC, we inhibited the PI3K/Akt pathway in rescue experiments, and evaluated the expression levels of epithelial-mesenchymal transition (EMT)-related proteins by western blot. Results: The expression of DLEU2 was aberrantly up-regulated in GC tissues and cells, which was correlated with the degree of tumor differentiation, cancer antigen 19-9 (CA19-9) and Lauren histologic classification of patients with GC. Silencing of DLEU2 induced apoptosis, attenuated viability, migration and invasion as well as inhibited the PI3K/Akt signaling pathway in GC cells. Mechanistically, the DLEU2/PI3K/Akt axis promoted the progression of GC and the EMT by down-regulating the expression of E-Cadherin and up-regulating those of N-Cadherin and Vimentin. Discussion and conclusions: LncRNA DLEU2 promoted the migration, invasion and EMT in GC by activating the PI3K/Akt pathway.

Upregulated LINC00922 Promotes Epithelial-Mesenchymal Transition and Indicates a Dismal Prognosis in Gastric Cancer.

Background LINC00922 has been found to promote epithelial-mesenchymal transition (EMT) in a variety of tumors. But its functions in gastric cancer (GC) remain unclear. We attempt to investigate the correlation between LINC00922 and GC via bioinformatics analysis, in vitro and in vivo experiments. Methods TCGA and GTEx databases were utilized to obtain the RNAseq and clinical data of GC, and then, identified the correlation of LINC00922 with patients' clinicopathological characteristics and prognosis. GSEA and GO/KEGG enrichment analyses were performed to explore the potential functions or signaling pathways that LINC00922 participated in GC. Infiltration levels of immune cells were employed by ssGSEA algorithm, and then Wilcoxon rank sum test was applied to analyze their correlations with LINC00922. Scratch and transwell assays were conducted to detect the invasion and migration abilities of GC cells. Western blot was performed to explore the expression level of EMT-related proteins. Furthermore, we constructed the xenograft tumor model and metastatic tumor model in nude mice to explore the effect of LINC00922 downregulating on metastasis of GC cells in vivo. Results Compared with normal tissues, LINC00922 was highly expressed in GC tissues and positively correlated with poor prognosis. The correlation existed between LINC00922 and immune infiltration in GC. Downregulation of LINC00922 inhibited the EMT process of GC cells. In addition, both in vitro and in vivo experiments showed that LINC00922 affects the invasion and migration abilities of GC. Conclusions LINC00922 promotes the migration, invasion, and EMT in GC and has the potential to be used as a prognostic biomarker and therapeutic target for GC.

Helicobacter pylori cytotoxin-associated gene A virulence and its association with the epithelial-mesenchymal transition in gastric cancer

Gastric cancer is currently one of the most prevalent malignancies worldwide with a high mortality rate. Helicobacter pylori (H. pylori) infection significantly contributes to the onset and progression of gastric cancer mainly due to the induction of chronic inflammatory responses. The pathogenicity of H. pylori is associated with a vast number of virulence factors among which cytotoxin-associated gene A (CagA) plays a crucial role. We conducted a literature review of PubMed, Web of Science, and Scopus on September 1st, 2021. There were no limits regarding the year and the language of publication. Articles included in this review concerned human and animal studies. The following search string was applied during the search: (gastric cancer) AND (epithelial-mesenchymal transition) AND (Helicobacter pylori) AND (cytotoxin-associated gene A). The final analysis included 135 articles independently reviewed by the authors. H. pylori CagA-positive strains seem to be more virulent compared to the CagA-negative strains. CagA pathogenicity includes the increased secretion of pro-inflammatory cytokines, induction of cancer stem cell-like properties, apoptosis prevention, or overactivation of particular oncogenic pathways. H. pylori might induce epithelial-mesenchymal transition (EMT) via numerous pathways, among which CagA-related pathogenicity is considered to be of high significance. Mechanisms associated with CagA action are involved in the maintenance of chronic H. pylori infection, subsequent EMT induction, and further onset and progression of gastric cancer. Because of a huge number of H. pylori strains with different virulence mechanisms, the clinical outcome of patients is also associated with the particular type of strain that infected a patient.

Collagen type IV alpha 1 (COL4A1) silence hampers the invasion, migration and epithelial–mesenchymal transition (EMT) of gastric cancer cells through blocking Hedgehog signaling pathway

ABSTRACT Gastric cancer (GC), which features high prevalence and mortality rate, remains the third most lethal cancer worldwide. The paper was designed to explore the impacts of collagen type IV alpha 1 (COL4A1) on GC, along with its potential mechanism. The mRNA and protein expressions of COL4A1 in GC cells were assessed using RT-qPCR and Western blot. After depleting COL4A1, RT-qPCR and Western blot were conducted again to check the transfection efficacy. With the application of CCK-8, wound healing and transwell, the capabilities of cells to proliferate, migrate and invade were appraised, respectively. Moreover, Western blot tested the protein levels of factors involved in migration, proliferation, epithelial–mesenchymal transition (EMT) and Hedgehog signaling. As a result, COL4A1 displayed elevated expression in GC tissues and cells, while its knockdown inhibited the cell viability, migration, invasion and EMT in GC. According to Gene Set Enrichment Analysis (GSEA), COL4A1 was involved in the regulation of Hedgehog signaling pathway, which was then further verified by the detection of Hedgehog-related proteins. To figure out the relationship between COL4A1 and Hedgehog signaling pathway, we used purmorphamine, an agonist of Hedgehog, to treat GC cells, finding that COL4A1 blocked Hedgehog signaling to inhibit the aggressive phenotypes of GC cells. In short, COL4A1 silence was testified to exhibit suppressive effects on the malignant process of GC, suggesting that COL4A1 might be a potent hallmark of GC therapy.

Retracted: miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway

The article entitled “miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway”, by Chen-Hui Bao and Lin Guo, has been retracted on the request of the Author in light of the changes to the University’s promotion policy, due to which the article needs further content. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. Kindly see Bentham Science Policy on Article retraction at the link https://benthamscience.com/journals/anti-canceragents-in-medicinal-chemistry/editorial-policies/ Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

The SKA3-DUSP2 Axis Promotes Gastric Cancer Tumorigenesis and Epithelial-Mesenchymal Transition by Activating the MAPK/ERK Pathway

Background: Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied. Methods: The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied in vitro and in vivo. Results: Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer. Conclusion: Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.