Migration Of Gastric Cancer Cells Research Articles

TRIM50 inhibits glycolysis and the malignant progression of gastric cancer by ubiquitinating PGK1.

Ubiquitination plays a pivotal regulatory role in tumor progression. Among the components of the ubiquitin-proteasome system (UPS), ubiquitin-protein ligase E3 has emerged as a key molecule. Nevertheless, the biological functions of E3 ubiquitin ligases and their potential mechanisms orchestrating glycolysis in gastric cancer (GC) remain to be elucidated. In this study, we conducted a comprehensive transcriptomic analysis to identify the core E3 ubiquitin ligases in GC, followed by extensive validation of the expression patterns and clinical significance of Tripartite motif-containing 50 (TRIM50) both in vitro and in vivo. Remarkably, we found that TRIM50 was downregulated in GC tissues, associated with malignant progression and poor patient survival. Functionally, overexpression of TRIM50 suppressed GC cell proliferation and indirectly mitigated the invasion and migration of GC cells by inhibiting the M2 polarization of tumor-associated macrophages (TAMs). Mechanistically, TRIM50 inhibited the glycolytic pathway by ubiquitinating Phosphoglycerate Kinase 1 (PGK1), thereby directly suppressing GC cell proliferation. Simultaneously, the reduction in lactate led to diminished M2 polarization of TAMs, indirectly inhibiting the invasion and migration of GC cells. Notably, the downregulation of TRIM50 in GC was mediated by the METTL3/YTHDF2 axis in an m6A-dependent manner. In our study, we definitively identified TRIM50 as a tumor suppressor gene (TSG) that effectively inhibits glycolysis and the malignant progression of GC by ubiquitinating PGK1, thus offering novel insights and promising targets for the diagnosis and treatment of GC.

PSME3 promotes glycolysis and migration of gastric cancer cells via regulating the EGFR/c-myc pathway

Gastric cancer (GC) is a common malignant tumor that is pernicious to the health of patients. Proteasome activator subunit 3 (PSME3) has been shown to exhibit higher expression and aggravate tumorigenesis in cancer progression. A major finding is that PSME3 is also highly expressed in GC tissues, which results in a worse prognosis. Nevertheless, the regulatory functions of PSME3 in GC progression remain unclear. This study aimed to investigate the impacts of PSME3 and related regulatory pathways on GC progression. From the Gene Expression Profiling Interactive Analysis (GEPIA) database, it was noted that PSME3 expression was up-regulated in GC tissues. Our findings suggested that in GC, PSME3 showed higher expression, resulting in a worse prognosis. Functional experiments revealed that PSME3 accelerates cell growth, migration and abnormal glycolysis in GC. PSME3 stimulates the epidermal growth factor receptor (EGFR)/c-myc pathway. In conclusion, GC cells exhibited higher PSME3 expression, which modulated the EGFR/c-myc pathway to fa

GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling.

The high mortality rate associated with gastric cancer (GC) has resulted in an urgent need to identify novel therapeutic targets for GC. This study aimed to investigate whether GAIP interacting protein, C terminus 1 (GIPC1) represents a therapeutic target and its regulating mechanism in GC. GIPC1 expression was elevated in GC tissues, liver metastasis tissues, and lymph node metastases. GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway, and inhibited the proliferation and migration of GC cells. Conversely, GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway, and promoted GC cell proliferation and migration. Furthermore, platelet-derived growth factor subunit BB (PDGF-BB) cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression. Moreover, GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice, while GIPC1 overexpression had contrasting effects. Taken together, our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.

Expression and clinical significance of ECHS1 in gastric cancer.

Background: Gastric cancer (GC), as one of the most common malignant tumors and the 3rd primary cause of death by cancer globally, poses a great threat to public health. Despite many advancements have been achieved in current treatment avenues for GC, the 5-year survival rates of GC patients remain substandard. Short-chain enoyl-CoA hydratase (ECHS1) exerts pro- or anti-cancer activities in different cancer backgrounds. However, its clinical significance and biological role in GC remain vague and need further investigation. Methods: The expression of ECHS1 in GC tumors and adjacent normal tissues was examined using the GEPIA platform and clinical samples. The effects of ECHS1 on GC cell proliferation and migration were evaluated using colony formation and transwell migration assays. Results: ECHS1 was upregulated in GC tumor tissues in both mRNA and protein levels and increased ECHS1 was markedly linked with tumor location, depth of tumor invasion, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage of GC patients. High ECHS1 expression was also linked with a shorter overal survival (OS), first progression (FP) and post progression survival (PPS). Further subgroup analysis showed that OS was significantly shorter in GC patients with high ECHS1 expression compared to those with low ECHS1 expression belonging to tumors with T3 stage, N2 stage or in instestinal Lauren subgroup. In addition, cytological experiments showed that there was higher ECHS1 expression in GC cell lines compared to the normal gastric epithelium (GES-1) cells, and ECHS1 can promote GC cell proliferation and migration in vitro. Conclusion: ECHS1 plays an oncogenic role in GC and might be a promising therapeutic target for GC.

ATP11A Promotes Epithelial-mesenchymal Transition in Gastric Cancer Cells via the Hippo Pathway.

Background: ATP11A, a P-type ATPase, functions as flippases at the plasma membrane to maintain cellular function and vitality in several cancers. However, the role of ATP11A in gastric cancer remains unknown. This study aimed to identify ATP11A related to the biological behavior of gastric cancer, and elucidate the underlying mechanism. Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression and prognosis of ATP11A. The biofunctions of ATP11A were explored through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). The expression of ATP11A were validated by immunohistochemistry (IHC), qRT-PCR and Western blotting. Transwell, wound healing, CCK8 and colony-formation were to detected the migration, invasion and proliferation of gastric cancer cells. The epithelial-mesenchymal transition (EMT) and Hippo pathway markers were examined by Western blotting. Results: The expression of ATP11A was higher in gastric cancer tissues than in normal tissues, and high ATP11A levels were related to worse prognosis of gastric cancer patients. Additionally, we proved that ATP11A promoted the migration, invasion and proliferation in gastric cancer cells. Furthermore, ATP11A was found to promote EMT by devitalizing the Hippo pathway. Conclusion: ATP11A promoted migration, invasion, proliferation and EMT via Hippo signaling devitalization in gastric cancer cells.

Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1.

Gastric cancer (GC) ranks as the fifth most common cancer and the fourth leading cause of cancer-related deaths globally. Despite advancements in molecular profiling, the mechanisms driving GC proliferation and metastasis remain unclear. This study identifies Early 2 Factor 4 (E2F4) as a key transcription factor that promotes GC cell proliferation, migration, and invasion by upregulating DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) expression. Bioinformatics and transcription factor analyses revealed E2F4 as a significant regulator of DSCC1. Functional assays confirmed E2F4's role in enhancing GC cell malignancy in vitro and in vivo. Knockdown and overexpression experiments demonstrated that E2F4 positively regulates DSCC1 at the transcriptional level, with ChIP-qPCR and dual luciferase reporter assays validating the binding sites on the DSCC1 promoter. These findings highlight the E2F4-DSCC1 axis as a potential therapeutic target to mitigate GC progression.

Downregulated lncRNA LINC00908 correlates with a poor prognosis and increasing malignancy of gastric cancer.

Long non-coding RNA LINC00908 is a functional biomarker in regulating tumour progression. Its dysregulation in gastric cancer implies its potential functional role. Few studies have noted the functional role of LINC00908 in gastric cancer. The potential of LINC00908 to serve as a biomarker in gastric cancer was evaluated. A total of 113 paired gastric cancer tissues and normal tissues were collected from patients with gastric cancer. LINC00908 levels were evaluated by polymerase chain reaction, and its significance in disease progression and patients' prognosis was assessed. In vitro, the function of LINC00908 in tumour-related cellular processes was evaluated with CCK8 and Transwell assay. Significant downregulation of LINC00908 was observed in gastric cancer and was negatively associated with disease development and overall survival of patients. LINC00908 showed significant inhibitory effects on the proliferation, migration, and invasion of gastric cancer cells. Additionally, miR-627-3p was sponged by LINC00908 and therefore mediated the function of LINC00908 in gastric cancer cells. LINC00908 functioned as a prognostic biomarker and tumour suppressor of gastric cancer, providing a therapeutic target for gastric cancer.

KRT80 expression works as a biomarker and a target for differentiation in gastric cancer.

Keratin 80 (KRT80) is a filament protein that participates in cell differentiation and the integrity of the epithelial barrier. Here, KRT80 expression was higher in gastric cancer compared with normal mucosa at both mRNA and protein levels by bioinformatic analysis, qRT-PCR and Western blot (p<0.05), however, the methylation of KRT80 was lower than in normal mucosa (p<0.05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in gastric cancer (p<0.05). KRT80 mRNA and protein expression was positively correlated with the differentiation of gastric cancer (p<0.05), while KRT80 methylation was negatively associated with gastric cancer differentiation and p53 mutation (p<0.05). The expression of KRT80 mRNA was positively linked to the short survival time of gastric cancers (p<0.05). The differential genes of KRT80 mRNA were involved in ligand-receptor interaction, estrogen signal pathway, peptidase, filament and cytoskeleton, keratinocyte differentiation, vitamin D receptor, muscle contraction, and B cell-mediated immunity (p<0.05). KRT80-related genes were classified into cell adhesion and junction, cadherin binding, skin and epidermis development, and so forth (p<0.05). KRT80 knockdown suppressed proliferation, anti-apoptosis, anti-pyroptosis, migration, invasion and epithelial-mesenchymal transition in gastric cancer cells (p<0.05). These findings indicated that up-regulated expression of KRT80 played a crucial part in gastric carcinogenesis, and might be considered as a biological marker for aggressive behaviors and poor prognosis. Its silencing might be used as an approach of target therapy for gastric cancer patients.

Curcumol Enhances the Sensitivity of Gastric Cancer to Cisplatin Resistance by Inducing Ferroptosis Through the P62/KEAP1/NRF2 Pathway.

Background: Chemoresistance represented one of the challenges in the treatment of advanced gastric cancer (GC). Curcumol (CUR) was found to have a certain sensitizing effect on chemoresistance, although the mechanism was not yet fully understood. Purpose: To clarify the ability of CUR to intervene in the sensitivity of GC cells to Cisplatin (CDDP) by regulating the induction of ferroptosis through the P62/KEAP1/NRF2 pathway. Methods: An in vitro resistant cell line was established and treated with CUR for intervention. The synergy was evaluated using synergyfinder3.0 software. The impact of the combined use of CUR and CDDP on the proliferation, migration, and invasion of resistant GC cells was determined. The effect of CUR on ferroptosis in resistant GC cell lines was evaluated by measuring changes in reactive oxygen species (ROS) levels, malondialdehyde (MDA) levels, iron ion levels, and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Western blotting was used to verify the expression changes of the ferroptosis-related indicator GPX4 and the differential expression of the antioxidant-related pathway P62/KEAP1/NRF2, validating the mechanism by which CUR induces ferroptosis in resistant GC cells. In vivo validation was performed using a xenograft mouse model. Results: The evaluation by synergy3.0 revealed a synergistic effect between CUR and CDDP. After treatment with CUR and CDDP, resistant GC cell lines exhibited reduced proliferation, migration, and invasion capabilities. Furthermore, the resistant GC cell lines underwent ferroptosis, with significant changes observed in ferroptosis-related indicators such as ROS, MDA, iron ions, and GSH/GSSG. The ferroptosis-related targets Glutathione Peroxidase 4 (GPX4) and the antioxidant pathway P62/KEAP1/NRF2 signaling pathway also showed significant changes. In in vivo validation, the combination of CUR and CDDP inhibited the growth of subcutaneous tumors and was found to be associated with the inhibition of subcutaneous xenografts and the GPX4 and P62/KEAP1/NRF2 signaling pathways. Conclusion: This study first revealed that CUR enhanced the sensitivity of cisplatin-resistant GC cells to CDDP by inducing ferroptosis. The combination of CUR and CDDP induces ferroptosis in cisplatin-resistant GC through the P62/KEAP1/NRF2 pathway.

PDE4B promotes the progression of gastric cancer via the PI3K/AKT/MYC pathway and immune infiltration.

Phosphodiesterase 4B (PDE4B) is a key enzyme involved in regulating intracellular cyclic adenosine monophosphate levels and plays a significant role in the diagnosis, classification, treatment, and prognosis of various cancers. However, the role of PDE4B in gastric cancer (GC) remains unclear. We used the GEPIA2 (Gene Expression Profiling Interactive Analysis 2) database to analyze the differential expression level of PDE4B across tumor samples and verified our findings via qPCR and immunohistochemical analysis. We also analyzed the correlation between PDE4B expression levels and clinical pathological parameters, and prognosis, in the database. The effects of PDE4B on GC proliferation, migration, and invasion were evaluated through in vitro and in vivo experiments. Enrichment analysis was performed using bioinformatic tools, and results were validated by western blot analysis. The correlation between PDE4B expression and immune cell infiltration was investigated using bioinformatics tools. PDE4B is highly expressed in GC and is significantly associated with deep infiltration, distant metastasis, tumor, node, metastasis (TNM) stage, and preoperative CA199 levels. Over-expression of PDE4B promotes proliferation, clonal formation, migration, and invasion of GC cells and is associated with poor prognosis. PDE4B promotes the infiltration of immune cells into the tumor microenvironment (TME) and the phosphorylation of PI3K/AKT pathway, increasing MYC expression. PDE4B can serve as an independent prognostic biomarker for GC. We found that PDE4B can promote immune cell infiltration of the TME and mediate malignancy in gastric cancer through the PI3K/AKT/MYC pathway.

Inflammation-Related Gene ADH1A Regulates the Polarization of Macrophage M1 and Influences the Malignant Progression of Gastric Cancer.

Gastric cancer (GC) is a malignant tumor originating from the gastric mucosa epithelium, and there is a low survival rate of GC patients after treatment, with a poor prognostic outcome. The inflammatory response within the tumor microenvironment plays an important role in GC progression. We downloaded GC-related datasets and inflammation-related genes from GEO, TCGA and MSigDB databases, performed differential analysis, protein-protein interaction analysis, immunoinfiltration analysis and Lasso analysis to screen inflammation-related hub genes affecting GC progression, and carried out qRT-PCR for validation. In order to explore the role of ADH1A, we constructed overexpressed plasmids, treated GC cells with cGMP/PKG pathway agonist 8-Br-cGMP, and tested cell functions with CCK8, EdU, Transwell, scratch assay and other experiments. On this basis, GC cells were co-cultured with monocyte THP-1 to explore the effect of ADH1A on the polarization of macrophages. ADH1A was significantly decreased in GC cells, and its expression trend was consistent with the results of bioinformatics analysis. Therefore, we chose ADH1A for subsequent functional validation. Overexpression of ADH1A in GC cells revealed ADH1A's role in inhibiting the activity, proliferation, migration and invasion of GC cells, promoting apoptosis and secretion of IL-6, IFN-γ, CCL5 and CSF2, and facilitating the transformation of macrophages to a pro-inflammatory M1 phenotype. ssGSEA results demonstrated the potential involvement of ADH1A in the cGMP/PKG signaling pathway, and significant changes in the expression of proteins related to the cGMP/PKG signaling pathway. The use of the cGMP/PKG signaling pathway agonist 8-Br-cGMP in ADH1A-overexpressing GC cells substantiated ADH1A's capacity to inhibit the cGMP/PKG signaling pathway, thereby suppressing the malignant progression of GC and promoting the transformation of macrophages to a pro-inflammatory M1 phenotype. ADH1A is able to influence the malignant progression of GC and the transformation of macrophages to the pro-inflammatory M1 phenotype through the cGMP/PKG signaling pathway.

MicroRNA-668-3p Mediates Macrophage M2 Polarization by Targeting NFKBIA to Affect Gastric Cancer Cell Proliferation and Migration.

MicroRNA-668-3p Mediates Macrophage M2 Polarization by Targeting NFKBIA to Affect Gastric Cancer Cell Proliferation and Migration.

CLEC4D as a Novel Prognostic Marker Boosts the Proliferation and Migration of Gastric Cancer via the NF-κB/AKT Signaling Pathway.

The functions of C-type lectin domain family 4 member D (CLEC4D), one member of the C-type lectin/C-type lectin-like domain superfamily, in immunity have been well described, but its roles in cancer biology remain largely unknown. This study aims to explore the role of CLEC4D in gastric cancer (GC). Bioinformatics preliminarily analyzed the expression of CLEC4D in gastric cancer. Immunohistochemical staining was used to detect the expression level and clinical pathological characteristics of CLEC4D in gastric cancer. The biological function of CLEC4D in gastric cancer cell lines was verified through in vitro and in vivo experiments. In this study, CLEC4D expression was found to be markedly increased in gastric cancer (GC) tissues compared with matched normal gastric tissues, and high CLEC4D expression independently predicted unfavorable overall survival in patients with GC. Knockdown of CLEC4D markedly inhibited GC cell proliferation and migration. Mechanistically, CLEC4D knockdown deactivated the Akt and NF-κB signaling pathways in GC cells. Together, these results demonstrate that aberrantly increased CLEC4D expression promotes cancer phenotypes via the Akt and NF-κB signaling pathways in GC cells.

Acting mechanism and clinical significance of hsa_circ_0005927 in the invasion and metastasis of gastric cancer.

Background: An increasing number of studies have demonstrated that differentially expressed circular RNAs (circRNAs) play critical roles in carcinogenesis. However, the biological function and clinical significance of hsa_circ_0005927 during gastric carcinogenesis remain unclear. The aim of this study was to investigate the acting mechanism and clinical significance of hsa_circ_0005927 in the invasion and metastasis of gastric cancer (GC). Methods: Hsa_circ_0005927 was detected in GC tissues, plasma and gastric juice from patients with GC, and its correlations with clinicopathological parameters were investigated. Receiver operating characteristic curves, Kaplan-Meier survival curves and a prognostic nomogram model were generated to analyze the diagnostic and prognostic value. Real-time cell analyzer, plate colony formation, and Transwell migration and invasion assays were utilized to assess GC cell proliferation, migration and invasion, respectively. Nucleoplasmic separation was applied to determine the distribution of hsa_circ_0005927 in cells. TargetScan and miRanda software were used for target microRNA (miRNA) prediction. Transcriptome sequencing and bioinformatics analysis were performed to annotate the functions of hsa_circ_0005927 in gastric carcinogenesis and metastasis from an RNomic perspective. Key target genes and immune cell infiltrations were analysed. Results: Hsa_circ_0005927 was found downregulated in high-grade intraepithelial neoplasia (HGIEN) tissues and GC tissues. Hsa_circ_0005927 levels in GC tissues were negatively correlated not only with lymphatic metastasis and distal metastasis but also with overall survival and disease-free survival. As a screening biomarker for GC, plasma hsa_circ_0005927 levels significantly increased in the early stages of GC, with a sensitivity and specificity of 52.38% and 76.19%, respectively. Hsa_circ_0005927 was mainly distributed in the cytoplasm, and structurally, it possesses multiple miRNA response elements (MREs) that interact with five miRNAs. A total of 421 downstream target genes of hsa_circ_0005927 were identified by transcriptome sequencing; and bioinformatics analysis suggested that these genes were involved mainly in the negative regulation of the T-cell apoptotic process, the interleukin-27-mediated signaling pathway, growth factor activity, guanylate cyclase activity, transcriptional misregulation in cancer, the cGMP-PKG signaling pathway, and the GnRH signaling pathway during gastric carcinogenesis and metastasis. GUCY1A2 and STK32A are key target genes significantly associated with immune infiltration. Conclusion: Our study revealed that hsa_circ_0005927 is a new player related to the invasion and metastasis of GC and is a potential indicator for early GC screening.

Ubiquitin-specific Protease 35 Promotes Gastric Cancer Metastasis by Increasing the Stability of Snail1.

Deubiquitinase (DUB) dysregulation is closely associated with multiple diseases, including tumors. In this study, we used data from The Cancer Genome Atlas and Gene Expression Omnibus databases to analyze the expression of 51 ubiquitin-specific proteases (USPs) in gastric cancer (GC) tissues and adjacent non-neoplastic tissues. The Kaplan-Meier Plotter database was used to analyze the association of the differentially expressed USPs with the overall survival of patients with GC. The results showed that five USPs (USP5, USP10, USP13, USP21, and USP35) were highly expressed in GC tissues and were associated with poor prognosis in patients with GC. Because the epithelial-mesenchymal transition enables epithelial cells to acquire mesenchymal features and contributes to poor prognosis, we investigated whether these USPs had regulatory effects on the key epithelial-mesenchymal transition transcription factor Snail1. Our results showed that USP35 exhibited the most significant regulation on Snail1. Overexpression of USP35 increased and its knockdown decreased Snail1 protein levels. Mechanistically, USP35 interacted with Snail1 and removed its polyubiquitinated chain, thereby increasing its stability. Furthermore, USP35 promoted the invasion and migration of GC cells depending on its DUB activity. USP35 knockdown exhibited the opposite effect. Snail1 depletion partially abrogated the biological effects of USP35. Experiments using nude mouse tail vein injections indicated that wild-type USP35, but not the catalytically inactive USP35-C450A mutant, dramatically enhanced cell colonization and tumorigenesis in the lungs of mice. In addition, USP35 positively correlated with Snail1 expression in clinical GC tissues. Helicobacter pylori infection increased USP35 and Snail1 expression levels. Altogether, we found that USP35 can deubiquitinate Snail1 and increase its expression, thereby contributing to the malignant progression of GC. Therefore, USP35 may serve as a viable target for GC treatment.

LncRNA H19 Promotes Gastric Cancer Metastasis via miR-148-3p/SOX-12 Axis.

Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. Methodology. A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. Key Results. In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR-148a-3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR-148a-3p. As expected, miR-148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR-148a-3p is the H19-associated miRNA in GC. We also confirmed that SOX-12 expression was upregulated in GC patient's samples. SOX-12 expression was positively correlated with expression of H19 and was able to directly bind to miR-148a-3p. Importantly, in vitro wound healing assay showed that knockout of SOX-12 could reverse the promoting effect of H19 overexpression on cell migration. In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR-138a-3p/SOX-12 axis.

High expression of ABL2 promotes gastric cancer cells migration, invasion and proliferation via the TGF-β and YAP signaling pathways.

Background: The Abelson-Related Gene (ABL2) is expressed in various malignancies. However, its role in gastric cancer (GC) regarding tumor proliferation, metastasis, and invasion remains unclear. Methods: ABL2 expression in clinical specimens was assessed using quantitative real-time fluorescence PCR (qRT-PCR). Western blotting and immunofluorescence assay determined protein levels. Additionally, Transwell migration and invasion, cell counting kit-8 (CCK-8) and colony-formation assays analyzed the effect of ABL2 on GC cells. Protein levels related to GC cells were assessed through Western blotting. The effects of si-ABL2 combined with GA-017 that activated YAP on cell migration, invasion and proliferation were investigated. Results: ABL2 expression was upregulated in human GC tissues compared to paracancer tissues, and it was positively related to tumor node metastasis classification (TNM) stage. Furthermore, high ABL2 levels promoted the proliferation, metastasis, and invasion capacity in GC cells. Elevated ABL2 expression enhanced the expression of MMP2, MMP9, and PCNA while decreasing TIMP1 and TIMP2 expression. It also increased the p-SMAD2/3 expression and YAP expression, decreased the expression of p-YAP in GC cells. Furthermore, GA-017 increased ABL2 expression in MGC-803 cells and counteracted the effects of si-ABL2 on cell migration, invasion and proliferation. Conclusion: These findings indicated that heightened ABL2 expression could activate TGF-β/SMAD2/3 and YAP signaling pathway, promoting epithelial mesenchymal transformation (EMT), and enhancing multiplication, metastasis, and invasion in GC cells.

Baicalein blocked gastric cancer cell proliferation and invasion through modulated platelet type 12-lipoxygenase.

Baicalein (BAI) is one of the main ingredients of Scutellaria baicalensis georgi. Its pharmacological effects have been widely reported in various cancers. However, the specific molecular mechanism of BAI in gastric cancer (GC) has not been defined. This study investigates BAI's inhibitory effect on gastric cancer and its potential mechanisms. Gastric normal (GES-1 cells) and cancer cells (MKN-74 and MGC-803 cells) were treated with different concentrations of BAI. Cell proliferation and migration were assessed by MTT, colony formation, wound healing, and transwell assays. Flow cytometry and Hoechst 33342 staining were used to detect the cell apoptosis. IF and WB tests were employed to detect EMT-related protein. Finally, the anti-tumor effects of BAI were verified in in vivo xenograft models. Our results show that the cell viability of MKN-74 and MGC-803 cells was significantly decreased in a time- and dose-dependent manner after BAI treatment by MTT assay. The expression levels of p12-LOX genes, which were determined by quantitative RT-PCR and WB, in MKN-74 cells were higher than those in GES-1 cells. As shown by the wound healing assay and Transwell assay, the treatment with BAI also significantly suppressed GC cell migration and invasion. Besides, BAI inhibited the phosphorylation of ERK1/2 and MEK1/2 in GC cells, as revealed by WB. Furthermore, BAI significantly inhibited tumor growth capacities in a xenograft model. BAI shows a significant anti-tumor effect and inhibition on tumor cell migration and invasion, which is probably through regulation of p12-LOX modulated epithelial-mesenchymal transformation.

Long-term MNNG exposure promotes gastric carcinogenesis by activating METTL3/m6A/miR1184 axis-mediated epithelial-mesenchymal transition

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

M-CSF secreted by gastric cancer cells exacerbates the progression of gastric cancer by increasing the expression of SHP2 in tumor-associated macrophages.

To investigate the effect of Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) in tumor-associated macrophages (TAMs), which is mediated by macrophage colony-stimulating factor (M-CSF) secreted by gastric cancer cells, on the development of gastric cancer and its molecular mechanism. The progression of gastric cancer was detected by nude mouse tumor-bearing experiments. Colony formation assay and cell counting kit-8 (CCK8) assay were used to detect the proliferation capacity of gastric cancer cells. The migration capacity of gastric cancer cells was examined by wound healing assay. Transwell migration and invasion assays were performed on gastric cancer cells. Detection of relevant protein expression using western blotting. Overexpression of SHP2 could promote the progression of gastric cancer in nude mice. The results of colony formation assay and CCK8 assay showed that overexpression of SHP2 could enhance the proliferation of gastric cancer cells. It was found by wound healing assay and Transwell assay that overexpression of SHP2 could facilitate the migration and invasion of gastric cancer cells. The results of Western blotting revealed that overexpression of SHP2 could increase the expressions of p-STAT3, s-PD-1, p-Src, p-Lyn, p-PI3K, p-AKT, Arginase-1, MMP1 and MMP3 but decrease the expressions of TBK1 and SOCS1 in TAMs, and also increase the expressions of CD9, TSG101 and s-PD-1 in exosomes. M-CSF secreted by gastric cancer cells can promote the proliferation, invasion and migration of gastric cancer cells by increasing the expression of SHP2 in TAMs.