Motility Of Gastric Cancer Cells Research Articles

ACAT2 suppresses the ubiquitination of YAP1 to enhance the proliferation and metastasis ability of gastric cancer via the upregulation of SETD7

The contributions of aberrantly expressed metabolic enzymes to gastric cancer (GC) initiation and progression have been widely appreciated in recent years. Acetyl-CoA acetyltransferase 2 (ACAT2) is one member of the acetyl- CoA thiolase family. Previous studies demonstrated that ACAT2 either promotes or suppresses tumor progression in different conditions. However, the function and mechanisms of ACAT2 in GC remain unknown. We found that the expression of this enzyme was significantly increased in GC tissues compared with normal counterparts, which prompted us to further investigate the roles of this protein in GC biology. In vitro functional studies showed that ACAT2 knockdown markedly halted the proliferation and the motility of GC cells; these functions favoring malignant phenotypes of GC cells were further validated in animal experiments. Mechanistically, ACAT2 depletion significantly reduced the transcription of SETD7, which is a histone methyltransferase and plays critical roles in GC cells. We found that the pro-tumoral functions of ACAT2 were largely dependent on SETD7. Moreover, SETD7 decreased the ubiquitination level of Yes-associated protein 1 (YAP1), thereby protecting YAP1 from proteasome degradation. Increased YAP1 protein expression remarkably activated the YAP1/TAZ-TEAD1 signaling pathway, which further boosted the malignant phenotypes in GC cells. In conclusion, these findings highlight the pro-tumoral functions and molecular underpinnings of ACAT2 in GC cells, and suggest that ACAT2 could be a promising target in GC treatment.

Downregulation of lncRNA EPB41L4A-AS1 promotes gastric cancer cell proliferation, migration and invasion.

The incidence of gastric cancer ranks the first among digestive tract tumors in China. However, there are no specific symptoms in the early stage of the tumor and the diagnosis process is complex, so more effective detection methods are very needed. In this study, a novel long noncoding RNA (lncRNA) was introduced as a diagnostic biomarker for gastric cancer, which brought new thinking to the exploration of its pathological mechanism and clinical prediction. The level of lncRNA EPB41L4A-AS1 (EPB41L4A-AS1) in gastric cancer serum and cells was verified via real-time quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve was performed based on the EPB41L4A-AS1 level, and the diagnostic possibility of EPB41L4A-AS was analyzed. The chi-square test evaluated the correlation between EPB41L4A-AS expression and clinical information. The cells were cultured and transfected in vitro, and the mediations of abnormal EPB41L4A-AS level on the viability and motility of gastric cancer cells were verified through cell counting kit-8 (CCK-8) and Transwell assay. Furthermore, luciferase activity assay was performed to confirm the sponge molecule microRNA-17-5p (miR-17-5p) of EPB41L4A-AS1. EPB41L4A-AS1 was decreased in gastric cancer, and low EPB41L4A-AS1 level indicated resultful diagnostic value. Overexpression of EPB41L4A-AS1 inhibited the activity of gastric cancer cells, while knockdown of EPB41L4A-AS1 promoted tumor deterioration. EPB41L4A-AS1 directly targeted and regulated the expression ofmiR-17-5p. This study elaborated that EPB41L4A-AS1 is lowly expressed in gastric cancer. Silencing EPB41L4A-AS1 was beneficial to cell proliferation, migration, and invasion. EPB41L4A-AS1 provides a new possibility for the diagnosis of gastric cancer patients by targeting miR-17-5p.

Tectorigenin suppresses the viability of gastric cancer cells in vivo and in vitro

Gastric cancer is currently the 4th most common malignant tumor with a poor prognosis in 2022. New and effective drugs are needed to combat this disease to treat advanced gastric cancer. Tectorigenin (Tec) has a series of pharmacological activities, such as anti-inflammatory and anticancer. However, the effect of Tec on the progression of gastric cancer is unclear. In this study, we investigated the role of Tec in regulating cell viability, cell cycle, and tumor growth of gastric cancer. To detect the role of Tec in the progression of gastric cancer in vitro and in mice, we performed several in vitro assays such as MTT, colony formation, wound closure, transwell, Immunoblot assays, and in vivo tumor growth assays. Our data confirmed that Tec restrained the viability of gastric cancer cells at concentrations of 100, 200, and 300 μM. It also denied the motility of gastric cancer cells. Tec treatment also induced the cell cycle arrest of gastric cancer cells. Mechanically, Tec could suppress the activation of the PI3K/Akt pathway and stop gastric cancer progression. We, therefore, thought Tec could serve as a drug for treating gastric cancer.

Actinoquinazolinone, a New Quinazolinone Derivative from a Marine Bacterium Streptomyces sp. CNQ-617, Suppresses the Motility of Gastric Cancer Cells.

A HPLC-UV guided fractionation of the culture broth of Streptomyces sp. CNQ-617 has led to the isolation of a new quinazolinone derivative, actinoquinazolinone (1), as well as two known compounds, 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one (2) and 7-methoxy-8-hydroxy cycloanthranilylproline (3). The interpretation of 1D, 2D NMR, and MS spectroscopic data revealed the planar structure of 1. Furthermore, compound 1 suppressed invasion ability by inhibiting epithelial-mesenchymal transition markers (EMT) in AGS cells at a concentration of 5 µM. In addition, compound 1 decreased the expression of seventeen genes related to human cell motility and slightly suppressed the signal transducer and activator of the transcription 3 (STAT3) signal pathway in AGS cells. Together, these results demonstrate that 1 is a potent inhibitor of gastric cancer cells.

Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.

Epithelial-mesenchymal transition-related long noncoding RNAs in gastric carcinoma.

As an evolutionarily phenotypic conversion program, the epithelial-mesenchymal transition (EMT) has been implicated in tumour deterioration and has facilitated the metastatic ability of cancer cells via enhancing migration and invasion. Gastric cancer (GC) remains a frequently diagnosed non-skin malignancy globally. Most GC-associated mortality can be attributed to metastasis. Recent studies have shown that EMT-related long non-coding RNAs (lncRNAs) play a critical role in GC progression and GC cell motility. In addition, lncRNAs are associated with EMT-related transcription factors and signalling pathways. In the present review, we comprehensively described the EMT-inducing lncRNA molecular mechanisms and functional perspectives of EMT-inducing lncRNAs in GC progression. Taken together, the statements of this review provided a clinical implementation in identifying lncRNAs as potential therapeutic targets for advanced GC.

Bacterial Involvement in Progression and Metastasis of Adenocarcinoma of the Stomach.

Simple SummaryInfectious bacteria influence primary gastric carcinogenesis, organotropism, and metastatic progression by altering the microenvironment at the primary and secondary tumors. Key species include Helicobacter pylori (H. pylori) and Mycoplasma hyorhinis (M. hyorhinis). Inflammation caused by H. pylori virulence factors, such as CagA, VacA, and oipA, disrupt epithelial integrity, which allows the primary tumor to progress through the metastatic process. Evidence supports the activation of aquaporin-5 by CagA-positive H. pylori infection, promoting epithelial–mesenchymal transition via the extracellular signal-regulated kinase/mitogen-activated protein kinase (MEK/ERK) pathway, thus laying the foundation for metastatic disease. M. hyorhinis has also been implicated in gastric neoplasia via β-catenin stabilization and subsequent activation of the WNT-signaling pathway, promoting gastric cancer cell motility and inciting cancer progression.Gastric cancer metastasis is a process in which the tumor microenvironment may carry significant influence. Helicobacter pylori (H. pylori) infection is well-established as a contributor to gastric carcinoma. However, the role that these bacteria and others may play in gastric carcinoma metastasis is a current focus of study. A review of the literature was conducted to elucidate the process by which gastric adenocarcinoma metastasizes, including its ability to utilize both the lymphatic system and the venous system to disseminate. Studies that investigate the tumor microenvironment at both the primary and secondary sites were assessed in detail. H. pylori and Mycoplasma hyorhinis (M. hyorhinis) were found to be important drivers of the pathogenesis of gastric adenocarcinoma by modifying various steps in cell metastasis, including epithelial–mesenchymal transition, cell migration, and cell invasion. H. pylori is also a known driver of MALT lymphoma, which is often reversible simply with the eradication of infection. M. hyorhinis has been implicated in gastric neoplasia via β-catenin stabilization and subsequent activation of the WNT-signaling pathway, promoting gastric cancer cell motility and inciting cancer progression. Fusobacterium nucleatum (F. nucleatum) and its association with worse prognosis in diffuse-type gastric adenocarcinoma are also reviewed. Recognition of the roles that bacteria play within the metastatic cascade is vital in gastrointestinal adenocarcinoma treatment and potential reoccurrence. Further investigation is needed to establish potential treatment for metastatic gastric carcinoma by targeting the tumor microenvironment.

Glycosyltransferases EXTL2 and EXTL3 cellular balance dictates heparan sulfate biosynthesis and shapes gastric cancer cell motility and invasion

Heparan sulfate (HS) proteoglycans (HSPGs) are abundant glycoconjugates in cells' glycocalyx and extracellular matrix. By acting as scaffolds for protein-protein interactions, HSPGs modulate extracellular ligand gradients, cell signaling networks, and cell-extracellular matrix crosstalk. Aberrant expression of HSPGs and enzymes involved in HSPG biosynthesis and processing has been reported in tumors, with impact in cancer cell behavior and tumor microenvironment properties. However, the roles of specific glycosyltransferases in the deregulated biosynthesis of HSPGs are not fully understood. In this study, we established glycoengineered gastric cancer cell models lacking either exostosin-like glycosyltransferase 2 (EXTL2) or EXTL3 and revealed their regulatory roles in both HS and chondroitin sulfate (CS) biosynthesis and structural features. We showed that EXTL3 is key for initiating the synthesis of HS chains in detriment of CS biosynthesis, intervening in the fine-tuned balance of the HS/CS ratio in cells, while EXTL2 functions as a negative regulator of HS biosynthesis, with impact over the glycoproteome of gastric cancer cells. We demonstrated that KO of EXTL2 enhanced HS levels along with concomitant upregulation of Syndecan-4, which is a major cell surface carrier of HS. This aberrant HS expression profile promoted a more aggressive phenotype, characterized by higher cellular motility and invasion, and impaired activation of Ephrin type-A 4cell surface receptor tyrosine kinase. Our findings uncover the biosynthetic roles of EXTL2 and EXTL3 in the regulation of cancer cell GAGosylation and proteoglycans expression and unravel the functional consequences of aberrant HS/CS balance in cellular malignant features.

Amygdalin suppresses the proliferation, migration and EMT of gastric cancer cells by inhibiting TGF-β/Smad signal pathway

Purpose: To investigate the effects of amygdalin on the proliferation, motility and epithelial mesenchymal transformation (EMT) of gastric cancer cells and to elucidate the operating mechanisms of action.Methods: Gastric cancer AGS cells were treated with amygdalin (2.5, 5 and 10 mg/L). MTT and colony formation assays were used to investigate the effect of amygdalin on gastric cancer cell proliferation, while wound healing and Transwell assays were also carried out to determine its effect on the motility of gastric cancer cells. Immunoblot assays were used to investigate the effects of amygdalin on epithelial mesenchymal transformation (EMT) process and TGF-β/Smad pathway in gastric cancer cells.Results: Treatment with amygdalin suppressed the proliferation of gastric cancer AGS cells (p < 0.05). Amygdalin suppressed the migration and invasion of AGS cells in vitro (p < 0.05). Additionally, amygdalin suppressed epithelial mesenchymal transformation (EMT) in AGS cells, and suppressed TGF-β/Smad pathway (p < 0.05), thereby suppressing growth, motility, and EMT in AGS cells.Conclusion: Amygdalin may be useful for the treatment of gastric cancer; however, further studies are required ascertain this.

FGA inhibits metastases and induces autophagic cell death in gastric cancer via inhibiting ITGA5 to regulate the FAK/ERK pathway

This study aims to investigate the expression levels of fibrinogen α chain (FGA) in human gastric cancer (GC) tissues and cell lines, clarify its role in gastric cancer progression, and explore its underlying mechanism. Bioinformatics analysis, Immunoblot, Immunohistochemical (IHC), and quantitative PCR assays were performed to assess the expression of FGA in human gastric cancer tissues and cell lines. CCK-8 and colony formation assays were performed to detect its role in the proliferation of gastric cancer cells. Wound healing, transwell, and Immunofluorescence were performed to detect its effects on gastric cancer cell motility and epithelial-mesenchymal transition (EMT) processes. Luciferase and CHIP assays were performed to confirm the transcriptional regulation of FGA on ITGA5. Immunoblot assays and double-label RFP-GFP-LC3 immunofluorescence analysis were conducted to detect its effects on gastric cancer cell autophagy and FAK/ERK pathway, and in vivo tumor growth assays were further performed. We found the low expression of FGA in human gastric cancer tissues and cell lines. FGA suppressed gastric cancer cell proliferation, motility, and EMT process, and stimulated cell autophagy. We further found that FGA suppressed the expression of Integrin-α5 (ITGA5) and inhibited the FAK/ERK pathway, therefore suppressing the progression of gastric cancer. The in vivo assays further confirmed that FGA suppressed tumor growth of gastric cancer cells in the BALB/c nude mice (18–22 g, female, 8-week-old) through suppressing ITGA5-mediated FAK/ERK pathway in mice. We demonstrated the mechanism underlying FGA suppressing gastric cancer progression, and therefore we thought FGA could serve as a tumor suppressor protein in gastric cancer.

Circ_0074027 binds to EIF4A3 and promotes gastric cancer progression.

Circular RNAs (circRNAs) have been reported to play an important role in the progression of numerous types of human cancer. The aim of the present study was to determine the effects of circRNA_0074027 (circ_0074027) in gastric cancer (GC), and to elucidate the underlying mechanisms of action. For this purpose, the expression of circ_0074027 in GC cell lines was detected using reverse transcription-quantitative PCR. The effects of circ_0074027 on the proliferation and migration of GC cells were investigated using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The Circular RNA Interactome was used to predict that eukaryotic translation initiation factor 4A3 (EIF4A3) could bind to circ_0074027, which was confirmed using an RNA immunoprecipitation assay. The expression and function of EIF4A3 in GC cells were also determined using western blot analysis, as well as CCK-8, colony formation, wound-healing and Transwell assays. The results revealed that circ_0074027 was highly expressed in GC cell lines in the form of a closed loop. In addition, circ_0074027-knockdown inhibited cellular proliferation and motility. Furthermore, EIF4A3 was predicted to be targeted by circ_0074027 and a positive association was identified between them. The overexpression of EIF4A3 reversed the effects of circ_0074027 on the proliferation and motility of GC cells. In conclusion, the findings of the present study demonstrated that circ_0074027 bound to EIF4A3 and promoted the proliferation and migration capacities of GC cells.

Plasma Exosomal CircNEK9 Accelerates the Progression of Gastric Cancer via miR-409-3p/MAP7 Axis.

Exosome-mediated transfer of circular RNAs (circRNAs) is related to gastric cancer (GC) development. CircRNA NIMA-related kinase 9 (circNEK9; hsa_circ_0032683) was reported to be up-regulated in GC. The biological role of circNEK9 and its underlying mechanisms in GC progression were explored. The levels of RNAs and proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and flow cytometry. Wound healing assay and transwell assays were conducted to analyze cell motility. Intermolecular interaction was verified by dual-luciferase reporter assay and RNA pull-down assay. Animal experiments were used to evaluate the role of circNEK9 in the growth of xenograft tumors in vivo. CircNEK9 was up-regulated in GC tissues and cell lines. CircNEK9 interference suppressed the proliferation and motility of GC cells. CircNEK9 silencing enhanced microRNA-409-3p (miR-409-3p) level through direct interaction. CircNEK9 silencing-mediated influences on the proliferation and metastasis of GC cells were partly overturned by the interference of miR-409-3p. MiR-409-3p directly interacted with microtubule-associated protein 7 (MAP7) messenger RNA (mRNA). MiR-409-3p-induced effects in GC cells were largely counteracted by the overexpression of MAP7. CircNEK9 silencing blocked GC tumor growth in vivo. Exosome-mediated transfer of circNEK9 promoted the motility of recipient GC cells. CircNEK9 accelerated the proliferation, migration, and invasion of GC cells through targeting miR-409-3p/MAP7 axis. Plasma exosomal circNEK9 promoted the migration and invasion of recipient GC cells.

NSD1 stimulated survival and migration of gastric cancer cells through WNT10B

Background and objective: To assess the expression of Nuclear receptor binding SET domain protein 1 (NSD1) in human gastric cancer tissues and cells and investigate its possible role in gastric cancer. Methods: TCGA database was used to assess the expression levels of NSD1 in human gastric cancer tissues. Immunoblot assays were performed to detect NSD1 expression levels in gastric cancer cell lines. MTT and colony formation assays were conduced to detect its role in the survival of gastric cancer cells. Wound closure and transwell were performed to investigate the effects of NSD1 on the motility of gastric cancer cells. Immunoblot assays were also conducted to confirm its effects on WNT10B/β-catenin pathway. Results: We found the high expression levels of NSD1 in human gastric cancer tissues and cell lines. NSD1 depletion suppressed the survival and motility of gastric cancer cells. Additionally, we revealed NSD1 activated the WNT10B/β-catenin pathway, therefore promoted gastric cancer progression. Conclusion: We revealed the high NSD1 expression in gastric cancer tissues and cells, and thought NSD1 could serve as a promising gastric cancer target.

Cancer-associated Fibroblast-derived Spondin-2 Promotes Motility of Gastric Cancer Cells.

Peritoneal dissemination (PD) occurs frequently in gastric cancer (GC) and is fatal. The interactions between tumor cells and stromal cells are critical for cancer progression. Our aim was to identify a novel PD-associated gene derived from stromal cells in GC. Among the candidate PD-associated genes identified in our previous study, we focused on spondin-2 (SPON2), an extracellular matrix-secreted protein. Clinicopathological and prognostic analyses of SPON2 mRNA expression were performed using GC datasets. Localization of SPON2 expression was assessed by immunohistochemistry. In vitro migration assay and immunofluorescence staining were also conducted using GC cell lines. SPON2 was expressed in and secreted from cancer-associated fibroblasts in GC. High expression of SPON2 in tumor tissues was correlated with PD, tumor size and poor prognosis in GC. The motility of GC cells was increased by treatment with a SPON2 recombinant protein in vitro. Cancer-associated fibroblast-derived SPON2 may promote PD, in part, by facilitating GC cell motility and serve as a predictive marker for PD in GC.

MiR-301a-5p/SCIN promotes gastric cancer progression via regulating STAT3 and NF-κB signaling.

Objective: Gastric cancer (GC) is a type of highly malignant cancer. Although the diagnostic and therapeutic methods are innovating, the outcome of GC patients is still poor. Therefore, our research was carried out to explore potential molecular mechanism in the diagnosis of GC.Materials and methods: Bioinformatics analyses were used to obtain microRNA and target mRNA of interest. The expression level of miR-301a-5p and Scinderin (SCIN) mRNA were detected by quantitative real-time PCR (qRT-PCR). Western blot assay was used to investigate SCIN protein level. Cell Counting Kit-8 assay (CCK-8) and colony formation assay were used to investigate cell proliferation ability. Transwell assay was employed to examine cell motility. The interaction between miR-301a-5p and SCIN mRNA was verified by dual-luciferase reporter assay.Results: The qRT-PCR analysis revealed that the expression of miR-301a-5p was higher in gastric cancer tissues than para-cancer tissues (P<0.05). Cox regression analysis showed upregulated miR-301a-5p was associated with larger tumor size (P=0.036) and more advanced TNM stage (P=0.048). The Kaplan-Meier analysis showed a correlation between increased miR-301a-5p expression and shorter overall survival (OS)(P=0.018). By using bioinformatic analysis, SCIN was predicted as one of the targets of miR-301a-5p. Overexpressing miR-301a-5p promoted proliferation and motility of GC cells while knockdown of SCIN exhibited the same performance. Further, we verified the alteration of miR-301a-5p and SCIN expression level could affect the epithelial-mesenchymal transition (EMT) progression on GC cells via STAT3 and NF-κB signaling.Conclusion: Highly expressed miR-301a-5p was associated with aggressiveness of GC. Upregulation of miR-301a-5p promoted malignant phenotype of GC by targeting SCIN. The present results indicated miR-301a-5p might be a promising molecule in the prognosis of GC.

Activity-Based Protein Profiling Reveals Potential Dasatinib Targets in Gastric Cancer.

Dasatinib is a multi-target kinase inhibitor, whose targets include BCR-ABL, SRC family kinases, and various cancer kinases. The elevated SRC activity in gastric cancer (GC) has prompted the need for the therapeutic application of dasatinib in GC. We observed that the efficacy of dasatinib varied with the GC cell lines. The differential effect of dasatinib was not correlated with the basal SRC activity of each cell line. Moreover, the GC cell lines showing the strong antitumor effects of dasatinib were refractory to other SRC inhibitors, i.e., bosutinib and saracatinib, suggesting that unexpected dasatinib’s targets could exist. To profile the targets of dasatinib in GC, we performed activity-based protein profiling (ABPP) via mass spectrometry using a desthiobiotin-ATP probe. We identified 29 and 18 kinases as potential targets in dasatinib-sensitive (SNU-216, MKN-1) and -resistant (SNU-484, SNU-601) cell lines, respectively. The protein–protein interaction mapping of the differential drug targets in dasatinib-sensitive and -resistant GC using the STRING database suggested that dasatinib could target cellular energy homeostasis in the drug-sensitive GC. RNAi screening for identified targets indicated p90RSK could be a novel dasatinib target, which is important for maintaining the viability and motility of GC cells. Further functional validation of dasatinib off-target actions will provide more effective therapeutic options for GC.

Abstract 3566: Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia

Abstract Purpose: Hypoxic environments are randomly scattered throughout carcinomas. Although hypoxia is cytotoxic to both cancer cells and normal cells, some types of cancer cells acquire characteristics that allow them to survive and progress in a hypoxic environment. Hypoxia is considered to be associated with aggressive tumor phenotypes of gastric carcinomas, including the ability to metastasize. Hypoxia is clinically associated with metastasis and poor patient outcome, however the underlying processes remain unclear. It has been reported that lysyl oxidase (LOX) is a hypoxia-responsive factor and is associated with the malignant progression of carcinoma. The aim of this study was to clarify the relationship between the epithelial–mesenchymal transition (EMT) and LOX in gastric cancer cells under hypoxia. Methods: Two gastric cancer cell lines, OCUM-2MD3 and OCUM-12, were used in an in vitro study. The effect of siLOX on the EMT and motility of gastric cancer cells under hypoxic condition was analyzed by RT-PCR, western blot, wound-healing assay, and invasion assay. Correlations between LOX expression and the clinicopathological features of 544 patients with gastric carcinoma were examined immunohistochemically. Results: Hypoxic conditions increased the number of polygonal or spindle-shaped cells of EMT in gastric cancer cells. The EMT of cancer cells induced by hypoxia was inhibited by treatment with LOX siRNA. Taken together, the number of migrating and invading gastric cancer cells in hypoxia was significantly decreased by LOX knockdown. LOX siRNA significantly increased the E-cadherin level and decreased the vimentin level of gastric cancer cells. LOX expression was significantly associated with invasion depth, tumor differentiation, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal metastasis. Multivariable analysis revealed that LOX was an independent parameter for overall survival. Conclusion: HIF-1α might increase the expression of LOX, which affects the EMT of gastric cancer cells in hypoxic conditions via down-regulation of E-cadherin level and up-regulation of vimentin level. LOX expression may be a useful prognostic factor for patients with gastric cancer. Citation Format: Masakazu Yashiro, Hiroaki Kasashima, Yurie Yamamoto, Kenji Kuroda, Tomohiro Sera, Atsushi Sugimoto, Shuhei Kushiyama, Shingo Togano, Tomohisa Okuno, Yuichiro Miki, Masaichi Ohira. Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3566.

CircSMC3 regulates gastric cancer tumorigenesis by targeting miR-4720-3p/TJP1 axis.

Circular RNAs (circRNAs) are identified to play an evident role in many human cancers, such as gastric cancer. However, the potential mechanisms underlying the circRNA‐induced pathogenesis in gastric cancers are still elusive. The present study is designed to unfold the mechanism by which circRNAs involve in gastric cancer progression. Using circRNAs microarray, we detected the dysregulated circRNAs and identified an upregulated circRNA, circSMC3 (hsa_circ_0000260), in gastric cancer tissues. Patients with high circSMC3 expression levels had a poor overall survival via Kaplan‐Meier survival analysis implied that gastric cancer. Functionally, loss of circSMC3 abolished the proliferation and motility of gastric cancer cells. Mechanically, circSMC3 decreased miR‐4720‐3p expression by acting as a miRNA sponge, and tight junction protein 1 (TJP1) 3′UTR was identified to be the target of miR‐4720‐3p, contributing to a circSMC3/miR‐4720‐3p/TJP1 axis. Thus, our results indicate that circSMC3 promotes gastric cancer cell proliferation and motility through miR‐4720‐3p/TJP1.

MiR-491 inhibits BGC-823 cell migration via targeting HMGA2.

miR-491 functions as a tumor suppressor in several types of cancer. However, its function and mechanism in gastric cancer proliferation and metastasis have not been well defined. The aim of this study was to explore the role and regulatory mechanism of miR-491 in cell proliferation and migration in gastric cancer. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the expression pattern of miR-491 in gastric cancer tissues. miR-491 overexpression vector, miR-491 inhibitor, and siHMGA2 were used; and MTT, wound healing, and transwell assays were employed to examine proliferation and migration for BGC-823 cells. A dual-luciferase reporter gene was used to measure the target relationship between miR-491 and HMGA2. Most gastric cancer patients exhibit decreased miR-491 expression. miR-491 overexpression inhibited cell proliferation and migration, whereas miR-491 inhibitor treatment produced the opposite effect. Mechanistically, HMGA2 was identified as a direct target of miR-491. Moreover, HMGA2 knockdown inhibited cell proliferation and migration, which was similar to the effect of miR-491 overexpression. HMGA2 was decreased after transfection of the miR-491 vector and increased after transfection of the miR-491 inhibitor. Our results suggest that miR-491 suppressed cell proliferation and cell motility in gastric cancer by targeting HMGA2. Silencing HMGA2 produced a similar effect to miR-491 overexpression on cell proliferation and migration. miR-491/HMGA2 signaling may be a potential therapeutic target for gastric cancer patients with decreased miR-491 expression.

Mycoplasma hyorhinis infection promotes gastric cancer cell motility via β-catenin signaling.

BackgroundWe previously identified that Mycoplasma hyorhinis infection promotes gastric cancer cell motility. The β‐catenin signaling pathway is critical to determining malignant cancer cell phenotypes; however, the association between M hyorhinis and the β‐catenin signaling pathway is unclear.MethodsWe performed subcellular fractionation and immunofluorescence staining to observe β‐catenin accumulation in the nucleus. The expression of downstream β‐catenin genes was detected by quantitative RT‐PCR. Gastric cancer cell motility was examined by transwell chamber migration and wound healing assays, and a co‐immunoprecipitation assay was used to detect the proteins associated with the membrane protein p37 of M hyorhinis.ResultsWe found that M hyorhinis infection promoted nuclear β‐catenin accumulation and enhanced the expression of downstream β‐catenin genes. M hyorhinis‐promoted gastric cancer cell motility was counteracted by treatment with the β‐catenin inhibitor XAV939 or β‐catenin knockdown. We further detected a protein complex containing LRP6, GSK3β, and p37 in M hyorhinis‐infected cells. M hyorhinis also induced LRP6 phosphorylation in a GSK3β‐dependent fashion. Knockdown of LRP6 or GSK3β abolished M hyorhinis‐induced cell motility.ConclusionOur results reveal that the β‐catenin signaling pathway could be activated by M hyorhinis infection, thereby contributing to M hyorhinis‐induced gastric cancer cell motility.