Biological Behavior Of Gastric Cancer Cells Research Articles

Development of oxidative stress- and ferroptosis-related prognostic signature in gastric cancer and identification of CDH19 as a novel biomarker

BackgroundFerroptosis is a unique mode of cell death that is iron-dependent and associated with oxidative stress and lipid peroxidation. Oxidative stress and ferroptosis are essential mechanisms leading to metabolic abnormalities in cells and have been popular areas in cancer research.MethodsInitially, 76 oxidative stress and ferroptosis-related genes (OFRGs) were acquired by intersecting the gene sets from oxidative stress and ferroptosis. Afterwards, optimal OFRGs were screened using PPI networks, and individuals were separated into two OFRG subtypes (K = 2). Subsequently, we successfully constructed and verified a prognostic signature comprising SLC7A2, Cadherin 19 (CDH19), and CCN1. To further uncover potential biomarkers of gastric cancer (GC), we examined the expression level of CDH19, investigated the effects of knocking down CDH19 on the biological behavior of GC cells, and explored whether CDH19 is involved in ferroptosis and oxidative stress processes.ResultsAccording to the findings, individuals in the low-risk scoring group have less infiltration of immune suppressive cells, fewer occurrences of immune escape and dysfunction, greater efficacy in chemotherapy and immunotherapy, and better survival outcomes. The qRT-PCR assay indicated that CDH19 expression was significantly higher in GC cells. Through experiments, we demonstrated that knocking down CDH19 can affect the transcription levels of ACSL4 and GPX4, increase intracellular iron ion concentration and accumulation of reactive oxygen species (ROS), and inhibit the proliferation and migration of GC cells.ConclusionWe developed an OFRG-related signature to predict the prognosis and treatment responsiveness of individuals with GC and identified CDH19 as a possible therapeutic target for GC.

POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration.

The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo. Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p, and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p, miR-29a-3p, PIK3R1, and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1, PIK3R1, and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. The POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.

Mapping the intellectual structure and emerging trends for the application of nanomaterials in gastric cancer: A bibliometric study.

Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these materials. However, the research hotspots and trends in the application of nanomaterials in gastric cancer (GC) remain obscure. To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in GC. Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric study. VOSviewer and CiteSpace were used for bibliometric and visualization analyses. From 2000 to 2022, the application of nanomaterials in GC developed rapidly. The keyword co-occurrence analysis showed that the related research topics were divided into three clusters: (1) The application of nanomaterials in GC treatment; (2) The application and toxicity of nanomaterials in GC diagnosis; and (3) The effects of nanomaterials on the biological behavior of GC cells. Complexes, silver nanoparticles, and green synthesis are the latest high-frequency keywords that represent promising future research directions. The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.

BMP6 inhibits gastric cancer growth and predicts good prognosis.

Gastric cancer (GC) is a common tumors in the digestive tract, and effective treatment methods are still lacking. Bone morphogenetic protein 6 (BMP6) is closely related to the occurrence and development of various tumors, but its relevance to GC is still unclear. The aim of the study was to explore the relationship between BMP6 and the occurrence and development of GC. In this study, we investigated the relationship between BMP6 and the prognosis of GC patients using bioinformatics technology and clinical tissue samples. We also explored the connection between BMP6 and the biological behavior of GC cells through molecular biology experiments and relevant in vivo animal experiments. Finally, we examined the mechanisms by which BMP6 inhibits the onset and progression of GC. Through analysis of The Cancer Genomics Atlas (TCGA) database, we observed that BMP6 is expressed at low levels in GC, and its low expression is associated with a poor prognosis in GC patients. Cell experiments demonstrated that BMP6 expression can influence the proliferation of GC cells both in vitro and in vivo. Furthermore, we discovered that BMP6 is linked to the nuclear factor-κB (NF-κB) pathway, and subsequent experiments confirmed that BMP6 can inhibit the biological activity of GC cells by activating the NF-κB pathway. Our findings suggest that BMP6 is a potential prognostic biomarker in GC and can regulate the biological activity of GC cells through the NF-κB pathway. BMP6 may serve as a promising therapeutic target for GC, and our study introduces novel ideas for the prevention and treatment of this disease.

Cancer-Associated Fibroblast-Secreted Exosomes Promote Gastric Cancer Cell Migration and Invasion via the IL-32/ESR1 Axis.

Exosomes secreted by cancer-associated fibroblasts (CAFs) play a critical part in cancer progression. This study aimed to explore the effects of CAF-exosomes on gastric cancer (GC) cell metastasis. AGS and HGC-27 cells were treated with exosomes and cell viability, migration, and invasion were evaluated using Cell-Counting Kit-8 and Transwell assays. Exosome-regulated mRNAs were explored using quantitative real-time PCR. The relationship between interleukin (IL)32 and estrogen receptor 1 (ESR1) was evaluated using co-immunoprecipitation and dual-luciferase reporter assays. The results of this study show that CAF-derived exosomes promote GC cell viability, migration, and invasion. Exosome treatment increased the levels of IL32, which interacted with ESR1 and negatively regulated ESR1 levels. Rescue experiments were conducted to demonstrate that CAF-exosomes promoted biological behaviors of GC cells by upregulating IL32 and downregulating ESR1 expression. In conclusion, CAF-derived exosomes promote GC cell viability, migration, and invasion by elevating the IL32/ESR1 axis, suggesting a novel strategy for metastatic GC treatment.

LncRNA LINC00342 regulates gastric cancer cell proliferation, migration and invasion by targeting miR-596

To investigate the expression levels of LINC00342 in gastric cancer (GC) tissues and cells and the pathways mediating its effects on biological behaviors of GC cells. Bioinformatic analysis was performed to identify the lncRNAs and their downstream miRNAs involved in regulation of biological behaviors of GC cells. qRT-PCR was used to analyze the differential expression of LINC00342 and miR-596 in GC cell lines, human gastric mucosal cells, and GC and adjacent tissues. In human GC MGC-803 and MGC-823 cells, the effects of LINC00342 overexpression, miR-596 overexpression, LINC00342 knockdown, or miR-596 knockdown on cell proliferation, migration, invasion and cell cycle changes were examined using Edu assay, CCK-8 assay, wound healing assay, Transwell assay, and flow cytometry. The regulatory interaction between LINC00342 and miR-596 was investigated using a dual-luciferase reporter assay. Informatic analysis identified LINC00342 as the candidate lncRNA regulating biological behaviors of GC cells, with miR-596 as its downstream miRNA. LINC00342 expression levels were significantly higher while miR-596 expression levels were lower in GC tissues and cell lines than in the paired adjacent tissues and human gastric mucosal cell lines (all P<0.05). In MGC-803 and MGC-823 cells, overexpression of LINC00342 significantly enhanced cell proliferation (P<0.05), migration (P<0.01), and invasion (P<0.001) and reduced the percentage of G0/G1 phase cells (P<0.01), while knocking down LINC00342 significantly suppressed cell proliferation (P<0.05), migration (P<0.01), and invasion (P<0.001) and increased G0/G1 phase cell percentage (P<0.01). Modulation of miR-596 expression levels produced the opposite effects. Dual-luciferase reporter assay confirmed the specific binding between LINC00342 and miR-596 (P=0.0067). In GC cells, LINC00342 regulates cell proliferation, migration, and invasion by targeting miR-596.

KAT2A Promotes the Succinylation of PKM2 to Inhibit its Activity and Accelerate Glycolysis of Gastric Cancer.

Gastric cancer (GC) is one of the main causes of cancer-related death. Lysine acetyltransferases 2A (KAT2A) is a succinyltransferase that plays an essential role in cancer development. The pyruvate kinase M2 (PKM2) is a glycolysis rate-limiting enzyme that mediates the glycolysis of cancers. This study aimed to explore the effects and mechanism of KAT2A in GC progression. The effects of biological behaviors of GC cells were evaluated by MTT, colony formation and seahorse assays. The succinylation modification was assessed by immunoprecipitation (IP). The interaction between proteins were detected by Co-IP and immunofluorescence. A pyruvate kinase activity detection kit was used to evaluate the activity of PKM2. Western blot was performed to detect the expression and oligomerization of protein. Herein, we confirmed that KAT2A was highly expressed in GC tissues and was associated with a poor prognosis. Function studies showed that knockdown of KAT2A inhibited cell proliferation and glycolytic metabolism of GC. Mechanistically, KAT2A could directly interacted with PKM2 and KAT2A silencing inhibited the succinylation of PKM2 at K475 site. In addition, the succinylation of PKM2 altered its activity rather than its protein levels. Rescue experiments showed that KAT2A promoted GC cell growth, glycolysis, and tumor growth by promoting PKM2 K475 succinylation. Taken together, KAT2A promotes the succinylation of PKM2 at K475 to inhibit PKM2 activity, thus promotes the progression of GC. Therefore, targeting KATA2 and PKM2 may provide novel strategies for the treatment of GC.

SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis.

Silent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD). Human immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism. SGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD. The SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC.

Circ_0006089 Facilitates Gastric Cancer Progression via Decoying miR- 515-5p and Up-regulating CXCL6.

Gastric cancer (GC) is the most common cancer globally. Recent research has suggested that circular RNAs (circRNAs) play crucial roles in GC tumorigenesis and progression. The present study is performed to clarify the possible mechanism of circRNA has_circ_0006089 (circ_0006089) in GC. The differentially expressed circRNAs were screened out by analyzing the dataset GSE83- 521. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect circ_0006089, miR-515-5p and CXCL6 expression levels in GC tissues and cell lines. CCK-8, BrdU and Transwell assays were adopted to examine the biological function of circ_0006089 in GC cells. The interaction between miR-515-5p and circ_0006089, as well as between CXCL6 and miR-515-5p, was confirmed through bioinformatics, RNA immunoprecipitation (RIP) assay, dual-luciferase reporter gene assay and RNA pull-down assay. Circ_0006089 was significantly upregulated in GC tissues and cells, and miR-515-5p was remarkably downregulated. After knocking down circ_0006089 or overexpressing miR-515-5p, the growth, migration and invasion of GC cells were markedly reduced. In terms of mechanism, miR-515- 5p was verified to be the target of circ_0006089, and CXCL6 was validated as miR-515-5p's downstream target gene. Inhibiting miR-515-5p reversed the inhibitory effect knocking down circ_0006089 had on GC cell proliferation, migration and invasion. Circ_0006089 facilitates the malignant biological behaviors of GC cells via the miR-515- 5p/CXCL6 axis. Circ_0006089 can probably act as one of the important biomarkers and therapeutic targets in GC treatment strategies.

Circ_0000467 regulates proliferation, migration, invasion, and apoptosis in gastric cancer by targeting the miR-622/ROCK2 axis.

Gastric cancer (GC) ranks fourth as a cause of cancer-induced mortality worldwide. Recently, some studies have demonstrated that circular RNAs (circRNAs) play vital roles in human cancers, including GC. The expression levels of circ_0000467, microRNA-622 (miR-622), and Rho-associated coiled-coil-containing protein kinase2 (ROCK2) were determined by RT-qPCR assay. The protein expression was quantified by western blot assay. The interaction relationship between miR-622 and circ_0000467 or ROCK2 was confirmed by dual-luciferase reporter assay and RIP assay. The biological behaviors of GC cells including proliferation, apoptosis, migration, and invasion were determined by EdU assay, colony-forming assay, flow cytometry, and transwell assay. The effects of circ_0000467 silencing in vivo were assessed by a xenograft experiment in nude mice. MiR-622 was downregulated and ROCK2 was upregulated in GC tissues and cells. Loss-of-function experiment revealed that overexpression of miR-622 decreased proliferation, migration, and invasion while it increased apoptosis in GC cells. Furthermore, ROCK2 was a functional target of miR-622, and upregulation of ROCK2 abolished miR-622-induced effects on GC cells. What's more, circ_0000467 was upregulated in GC, and inhibition of miR-622 reversed silencing of circ_0000467-caused effects on GC cells, suggesting that miR-622 was a target of circ_0000467. The suppression of circ_0000467 was able to slow the tumor growth in vivo. Mechanistically, circ_0000467 functioned as an oncogenic regulator in GC by specifically binding to miR-622 to upregulate ROCK2, which might be novel diagnostic markers for GC.

PVT1/miR-16/CCND1 axis regulates gastric cancer progression.

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been reported to be a vital modulator in tumorigenesis of gastric cancer (GC). However, the detailed regulatory mechanism of PVT1 in GC remains largely unclear. In this work, the expressions of PVT1 and microRNA-16 (miR-16) were detected by quantitative real-time PCR (qRT-PCR) in GC tissues and cell lines. GC cell lines NCI-N87 and MKN45 cell lines were chosen for the following assays. After PVT1 was overexpressed or depleted, CCK-8 and Transwell assays were performed to examine the cell viability and invasive capacity. Cell cycle was analyzed by flow cytometry. The expression of cyclin D1 (CCND1) at mRNA and protein levels was measured by qRT-PCR and western blot. The competitive endogenous RNA molecular mechanism among PVT1, miR-16 and CCND1 was verified by bioinformatics analysis, luciferase-reporter gene assay and RNA immunoprecipitation assay. In the present study, it was revealed that PVT1 expression was remarkably evaluated in GC tissues and cell lines than that in the corresponding control group. PVT1 positively regulated the proliferation, migration and cell cycle progression of GC cells. Besides, miR-16 was identified as a target of PVT1, and CCND1 was identified as a target of miR-16. The depletion of PVT1 promoted the expression of miR-16 and suppressed CCND1 expression. Moreover, either miR-16 inhibitor or CCND1 overexpression plasmid could reverse the promoting effects of PVT1 on the malignant biological behaviors of GC cells. In conclusion, PVT1 promoted CCND1 expression by negatively regulating miR-16 expression to enhance the viability, invasion and cell cycle progression of GC cells.

Krüppel-Like Factor 2 Is a Gastric Cancer Suppressor and Prognostic Biomarker.

Gastric cancer (GC) is a common digestive tract tumor. Due to its complex pathogenesis, current diagnostic and therapeutic effects remain unsatisfactory. Studies have shown that KLF2, as a tumor suppressor, is downregulated in many human cancers, but its relationship and role with GC remain unclear. In the present study, KLF2 mRNA levels were significantly lower in GC compared to adjacent normal tissues, as analyzed by bioinformatics and RT-qPCR, and correlated with gene mutations. Tissue microarrays combined with immunohistochemical techniques showed downregulation of KLF2 protein expression in GC tissue, which was negatively correlated with patient age, T stage, and overall survival. Further functional experiments showed that knockdown of KLF2 significantly promoted the growth, proliferation, migration, and invasion of HGC-27 and AGS GC cells. In conclusion, low KLF2 expression in GC is associated with poor patient prognosis and contributes to the malignant biological behavior of GC cells. Therefore, KLF2 may serve as a prognostic biomarker and therapeutic target in GC.

MiR-196a-5p Correlates with Chronic Atrophic Gastritis Progression to Gastric Cancer and Induces Malignant Biological Behaviors of Gastric Cancer Cells by Targeting ACER2.

As the prognosis of early gastric cancer (EGC) is significantly better than that of advanced gastric cancer (AGC), the development of biomarkers to monitor the progression of chronic atrophic gastritis (CAG) to gastric cancer (GC) is essential. Stomach tissue miRNA and mRNA sequences from patients with chronic non-atrophic gastritis (CNAG), CAG, precancerous lesions of gastric cancer (PLGC), and GC were analyzed. A publicly available GC-related miRNA microarray dataset was obtained from the Gene Expression Omnibus database. Spearman's correlation and differential gene analyses, and clinical validation were used to identify novel miRNAs correlating with CAG progression to GC. miRNA targets were predicted using weighted gene co-expression analysis and databases. A dual-luciferase reporter assay was performed to check for direct interaction between miR-196a-5p and ACER2. The CCK-8 and wound healing assays, and flow cytometry were performed to evaluate cell proliferation, migration, and apoptosis. miR-196a-5p was correlated with CAG progression to GC. Overexpression of miR-196a-5p promoted GC cell proliferation and migration and inhibited apoptosis, whereas suppression of miR-196a-5p exerted the opposite effect. Based on the prediction and luciferase assays, ACER2 was identified as the target of miR-196a-5p. ACER2 was downregulated in GC cell lines. Knockdown of ACER2 increased GC cell proliferation rates and migration ability and inhibited apoptosis, while ACER2 overexpression led to the opposite effect. miR-196a-5p correlated with CAG progression to GC and induced malignant biological behaviors of GC cells by targeting ACER2, providing a novel monitoring biomarker and target for GC prevention.

E3 ubiquitin ligase TRIM55 promotes metastasis of gastric cancer cells by mediating epithelial-mesenchymal transition

Gastric cancer (GC) is considered a major global health problem. The role of TRIM55, a member of the three-domain protein family, in GC is unknown. To determine the expression of TRIM55 in GC tissues and its relationship with clinicopathological characteristics, and to investigate the effects of TRIM55 on the malignant biological behavior of GC cells. Differential expression of TRIM55 in GC and para-cancer tissues was detected by immunohistochemistry, and the relationship between TRIM55 level and clinicopathological characteristics and prognosis was analyzed. Gain-of-function, loss-of-function, cell counting kit-8 assay, colony formation, transwell assay, wound healing assay, and western blot analysis were used to assess the potential role of TRIM55 in the development of GC. TRIM55 expression was significantly increased in GC tissues compared with adjacent normal tissues. High expression of TRIM55 was associated with advanced pathological stage and poor prognosis. Overexpression of TRIM55 promoted invasion and metastasis of GC cells in vitro by regulating epithelial-mesenchymal transition (EMT), whereas knockdown of TRIM55 had the opposite effect. Our data showed that TRIM55 is highly expressed in GC tissues, and is associated with poor prognosis. TRIM55 plays the role of an oncogene in GC, and it promotes metastasis of GC through the regulation of EMT. TRIM55 may be a possible target for the diagnosis and prognosis of GC patients.

PRSS2 overexpression relates to poor prognosis and promotes proliferation, migration and invasion in gastric cancer

Serine protease 2 (PRSS2) plays a pivotal role in tum or pathogenesis as a serine protease. In this paper, we investigated the expression and role of PRSS2 in gastric cancer (GC). Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry (IHC) were performed to detect PRSS2 expression in GC tissues. The correlations between PRSS2 and clinicopathological variables and prognosis were analyzed. The effects of PRSS2 on gastric cancer in vitro and in vivo were detected by Cell Counting Kit-8 (CCK-8), colony formation assay, migration and invasion test, and nude mouse experiment. We observed that the PRSS2 mRNA and protein levels were upregulated in GC tissues, and PRSS2 expression was associated with GC N stage. Patients with high PRSS2 expression have a poor prognosis. Finally, the regulatory effect of PRSS2 on the biological behaviors of GC cells was assessed in GC cells transfected with lentiviral interference fragments of PRSS2. The results suggested that PRSS2 knockdown decreased the proliferation, migration and invasion of GC cells and downregulated MMP-9 expression. In summary, PRSS2 overexpression is associated with poor postoperative prognosis in GC patients and can be used as a potential biomarker to assess the prognosis of GC.

Profiling and Characterization of microRNAs Responding to Sodium Butyrate Treatment in Gastric Cancer Cells.

Short-chain fatty acids exert anti-cancer effects on tumor cells. We aimed to reveal the signaling network altered by butyrate in Gastric Cancer (GC) using small RNA sequencing (sRNA-seq). The effects of butyrate on the biological behavior of NCI-N87 and KATO III cells in vitro were assessed by functional assays and half-maximal inhibitory concentrations (IC50) of butyrate in KATO III cells were calculated. sRNA-seq was performed on KATO III cells. Differentially expressed miRNAs (DE-miRNAs) were identified between butyrate treatment and control groups using DESeq2, and miRNA targets were predicted. A protein-protein interaction (PPI) network of DE-miRNA targets was created using Metascape. Key MCODE complexes were identified using the MCODE algorithm and cluster Profiler. The relationship between DE-miRNA and GC overall survival (OS) was evaluated using Kaplan-Meier curves. Butyrate dose-dependently inhibited NCI-N87 and KATO III cell viability. KATO III cells were more sensitive to butyrate than NCI-N87 cells. Butyrate promoted apoptosis and inhibited KATO III cell migration. Total 324 DE-miRNAs were identified in KATO III cells, and 459 mRNAs were predicted as targets of 83 DE-miRNAs. Two key protein complexes were identified in a PPI network of the 459 targets. A key signaling network responding to butyrate was generated using targets in these key complexes and their miRNA regulators. The DE-miRNAs in the key signaling network were related to the OS of GC. Butyrate altered the biological behavior of GC cells, which may be achieved by regulating miRNAs and related oncogenic pathways.

Long non-coding RNA SNHG1/microRNA-195-5p/Yes-associated protein axis affects the proliferation and metastasis of gastric cancer via the Hippo signaling pathway.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) has been found to be highly expressed in gastric cancer (GC). However, the study for exploring the effects of SNHG1 and microRNA (miR)-195-5p on GC is limited. This research commits to unravel the regulatory effects of SNHG1, miRNA-195-5p, and Yes-associated protein 1 (YAP1) on GC. SNHG1, miR-195-5p and YAP1 levels in GC tissues and GC cells were detected. The GC cells were treated with various constructs altering SNHG1 or miR-195-5p expression to determine the biological activities of GC cell in vitro. The effect of SNHG1 inhibition on subcutaneous tumorigenesis of GC cells in a nude mouse model in vivo was detected. The binding relation among SNHG1, miR-195-5p, and YAP1 was validated. SNHG1 and YAP1 levels were elevated and miR-195-5p level was reduced in GC. Reduction of SNHG1 or elevation of miR-195-5p retarded GC cell biological activity in vitro. Downregulated SNHG1 suppressed tumor growth in vivo. SNHG1 bound to miR-195-5p, and miR-195-5p directly targeted YAP1. The downregulated SNHG1 hinders the biological behaviors of GC cells via the modulation of the miR-195-5p/YAP1 axis.

Knockdown and inhibition of hydroxytryptamine receptor 1D suppress proliferation and migration of gastric cancer cells

Serotonin (5-hydroxytryptamine, 5-HT) and its receptors play important roles in the development and progression of malignant tumors. The effect of the 5-HT receptor 1D (HTR1D), a member of the serotonin receptor family, on gastric cancer (GC) is not clear. Analysis of clinical data has shown that high expression of HTR1D was associated with poor prognosis in patients with GC and was an independent risk factor for reduced overall survival (OS) and disease-free survival (DFS). The present study assessed the effects of HTR1D knockdown and the HTR1D inhibitor GR127935 on the biological behavior of GC cells, which both impaired the proliferation and migration of GC cells. RNA sequencing showed that GR127935 inhibited tumor progression by limiting DNA replication and the cell cycle, inducing ferroptosis, and affecting tumor metabolism. Taken together, these findings showed that HTR1D has a potent oncogenic effect on GC and may provide a novel therapeutic target.

LINC01857 promotes the proliferation, migration, and invasion of gastric cancer cells via regulating miR-4731-5p/HOXC6.

The great importance of long non-coding RNAs (lncRNAs) in tumorigenesis has been acknowledged gradually. LINC01857 is previously reported to be highly expressed in gastric cancer (GC), while the regulatory mechanism of LINC01857 in GC is largely unknown. In this study, we detected high expression of LINC01857 from the GC microarray GSE109476. Additionally, LINC01857 expression is remarkably upregulated in GC cell lines (AGS, MKN-45, HGC-27, and SGC-7901) compared with the normal gastric mucosal cell line GES-1. Functionally, LINC01857 knockdown suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) of GC cells, while LINC01857 overexpression promoted the proliferation, migration, invasion, and EMT of GC cells. Furthermore, our data demonstrate that LINC01857 targeted miR-4731-5p and subsequently increased the expression of HOXC6 in GC. Rescue experiments showed that miR-4731-5p inhibition and HOXC6 overexpression could reverse the biological behavior of GC cells induced by LINC01857 knockdown. In conclusion, we demonstrated that LINC01857 sponged miR-4731-5p to promote the expression of HOXC6 and eventually acts as an oncogene in GC.

Long intergenic non-protein coding RNA 662 accelerates the progression of gastric cancer through up-regulating centrosomal protein 55 by sponging microRNA-195-5p

ABSTRACT Long non-coding RNAs (lncRNAs) are important players in regulating diverse human diseases, including cancers. Nonetheless, the function of long intergenic non-protein coding RNA 662 (LINC00662) in gastric cancer (GC) carcinogenesis and progression remains to be delineated. In the present study, LINC00662, microRNA-195-5p (miR-195-5p) and centrosomal protein 55 (CEP55) mRNA expression levels were quantified by qRT-PCR. GC cell proliferation, migration and invasion were analyzed by CCK-8, BrdU and Transwell assays. Besides, dual-luciferase reporter and RNA pull-down assays were conducted for verifying the targeting relationships of LINC00662, miR-195-5p and CEP55. The regulatory functions of LINC00662 and miR-195-5p on CEP55 were examined utilizing Western blot. In this study, it was revealed that LINC00662 expression level was elevated in GC tissues and cells. LINC00662 overexpression facilitated the malignant biological behaviors of GC cells whereas knockdown of LINC00662 worked oppositely. In terms of mechanism, LINC00662 targeted miR-195-5p to modulate CEP55 expression. In conclusion, LINC00662 facilitates the malignant biological behaviors of GC cells via miR-195-5p/CEP55 axis, and therefore, it may be a promising target for GC treatment.