Migration Of Gastric Carcinoma Cells Research Articles

Retraction: Salidroside inhibits the proliferation and migration of gastric carcinoma cells and tumor growth via the activation of ERS-dependent autophagy and apoptosis.

[This retracts the article DOI: 10.1039/C9RA00044E.].

CDK12 Promotes the Proliferation, Migration, and Angiogenesis of Gastric Carcinoma via Activating the PI3K/AKT/mTOR Signaling Pathway.

Cyclin-dependent kinase 12 (CDK12) has been found to regulate tumor progression. However, its function in gastric carcinoma (GC) remains controversial. This work aimed to explore the exact effect of CDK12 on GC progression. We detected the expression of CDK12 in GC cells and normal gastric mucosal epithelial cells. Then CDK12 function on GC cell proliferation, migration, and angiogenesis was researched by colony formation experiment, Transwell experiment, and angiogenesis assay. Moreover, CDK12 effect on the PI3K/AKT/mTOR pathway activity was explored by western blot. Further, we used LY294002 (10μM) to treat GC cells to verify whether CDK12 regulates GC progression by activating the PI3K/AKT/mTOR pathway. Additionally, CDK12 effect on the expression of prognostic factors of GC was detected by western blot, including alkaline phosphatase (ALP) and Ki67. Quantitative real-time polymerase chain reaction and western blot were utilized to evaluate the expression of mRNAs and proteins. As a result, CDK12 was upregulated in GC cells. CDK12 overexpression facilitated the proliferation, migration, and angiogenesis of GC cells. However, CDK12 silencing showed an opposite result. CDK12 overexpression activated the PI3K/AKT/mTOR pathway, but CDK12 silencing inactivated it in GC cells. The blockage of the PI3K/AKT/mTOR pathway induced by LY294002 treatment counteracted the promotion of CDK12 on the proliferation, migration, and angiogenesis of GC. Further, CDK12 silencing suppressed the expression of ALP and Ki67 proteins in GC cells. Taken together, CDK12 promotes the proliferation, migration, and angiogenesis of GC by activating the PI3K/AKT/mTOR pathway. It may be a novel target for GC treatment.

LINC00460 mediates HMGA2 expression through binding to miRNA-143-5p competitively in gastric carcinoma.

Compelling evidence has manifested a strong association between aberrant expression of long noncoding RNAs (lncRNAs) and gastric carcinoma (GC) development. Nonetheless, biological impacts of differentially expressed lncRNAs (DElncRNAs) on GC are not scrutinized. Bioinformatics methods were employed for differential expression analysis and target gene prediction. MTT, colony formation, and Transwell methods were implemented for GC cell proliferation, migration, and invasion assessment. Western blot was implemented to test the protein level. The binding of genes was tested with dual-luciferase and RNA binding protein immunoprecipitation (RIP) approaches. Noticeably high level of LINC00460 was observed in GC tissues and cells. LINC00460 silencing constrained proliferation, migration, and invasion of GC cells. FISH and nuclear-cytoplasmic separation assays confirmed the main presentation of LINC00460 in the cytoplasm. Bioinformatics predicted that LINC00460 had binding sites to miRNA-143-5p, which was upregulated in GC. Dual luciferase and RIP experiments also confirmed the binding relationship. Concurrent silencing of LINC00460s and miRNA-133-5p rescued the repressive influence of sh-LINC004600 on GC cell proliferation, migration, and invasion. HMGA2 was predicted to be a target gene downstream of miRNA-143-5p, their binding relationship was validated via dual luciferase assays. Silencing HMGA2 constrained GC cell proliferation, invasion, and migration. LINC00460 modulated HMGA2 expression via binding miRNA-143-5p, thereby affecting proliferation, invasion, and migration of GC cells. These findings validated that LINC00460 could regulate HMGA2 via sponging miRNA-143-5p to facilitate GC proliferation, invasion, and migration, which provides a deeper understanding of lncRNAs in the development of GC.

Impact of Amarogentin on Gastric Carcinoma Cell Multiplication, Apoptosis and Migration via circKIF4A/miR-152-3p

Objective The active ingredients extracted from natural plants have anti-GC actions and can slow down gastric carcinoma (GC) progression. To investigate the impact of Amarogentin (AG) on GC cell multiplication, apoptosis and migration and the possible mechanisms. Methods qRT-PCR quantification of circKIF4A and miR-152-3p in GC tissues and normal counterparts as well as HGC-27 (human GC cell strain) and GES-1 (human gastric mucosal epithelial cell strain) was performed. HGC-27 cells were intervened by AG of various concentrations. si-NC, si-circKIF4A were further transfected into HGC-27 cells. Besides, pcDNA and pcDNA-circKIF4A were transfected into HGC-27 cells, after which 60 mmol/L AG was added for intervention. Cell multiplication, clone formation, as well as apoptosis and migration measurements were made by MTT, plate clone formation, flow cytometry and Transwell assays, respectively; Double luciferase reporter assay was performed for targeting relationship identification between circKIF4A and miR-152-3p; Western blots were carried out to measure Bax and Bcl-2 protein levels. Results circKIF4A increased (P <0.05) and miR-152-3p decreased (P <0.05) in GC tissues and cell strains. Concentration-dependently, AG intervention contributed to enhanced cell multiplication inhibitory rate, apoptosis rate, miR-152-3p expression and Bax protein level (P <0.05), together with declined number of cell clones formed, migrating cells, circKIF4A expression and Bcl-2 protein level (P <0.05). After transfection of si-circKIF4A, cell multiplication inhibition rate, apoptosis rate and Bax protein level enhanced (P <0.05), while cell clones formed and migrating cells as well as Bcl-2 protein level reduced (P <0.05). miR-152-3p can be controlled by circKIF4A; pcDNA-circKIF4A transfection antagonized AG's effects on HGC-27 cell multiplication, clone formation, apoptosis and migration. Conclusion AG can decrease GC multiplication, clone formation and migration and induce apoptosis via modulating circKIF4A/miR-152-3p expression.

Male-specific long non-coding RNA testis-specific transcript, Y-linked 15 promotes gastric cancer cell growth by regulating Wnt family member 1/β-catenin signaling by sponging microRNA let-7a-5p

ABSTRACT The present study is aimed to investigate the regulatory effects and related mechanism of long non-coding RNA testis-specific transcript, Y-linked 15 (TTTY15) in gastric carcinoma (GC) cell proliferation, migration, invasion, apoptosis and epithelial–mesenchymal transition (EMT). TTTY15 expression in GC tissue samples and cells was detected by quantitative real-time PCR (qRT-PCR), and the correlation between TTTY15 expression and GC clinicopathological indicators was analyzed. Cell counting kit-8 (CCK-8), BrdU, flow cytometry and Transwell assays were performed for detecting GC cell proliferation, migration, invasion and apoptosis. Western blot was performed for detecting the expressions of EMT-associated proteins (N-cadherin and E-cadherin), Wnt family member 1 (Wnt1) protein and β-catenin protein. Bioinformatics analysis was conducted to predict, and RNA immunoprecipitation (RIP) assay and dual-luciferase reporter gene assay were performed to verify the targeted relationships of microRNA let-7a-5p (let-7a-5p) with TTTY15 and Wnt1 mRNA 3'UTR. It was found that TTTY15 expression was significantly up-regulated in GC tissues and cells, and was associated with advanced TNM stage and poor tumor differentiation. TTTY15 overexpression promoted GC cell proliferation, migration and invasion, the expressions of N-cadherin, Wnt1 and β-catenin protein, and inhibited the apoptosis and E-cadherin expression, while knocking down TTTY15 had the opposite effects. TTTY15 directly targeted let-7a-5p and negatively regulated its expression. Wnt1 was the target gene of let-7a-5p, and TTTY15 could indirectly and positively regulate Wnt1 expression. In conclusion, TTTY15 promotes GC progression, by regulating the let-7a-5p/Wnt1 axis to activate the Wnt/β-catenin pathway.

Expression of tight junction transmembrane protein Claudin-1 in gastric carcinoma and effects on tumor cell proliferation, invasion and migration

Abstract Background: Claudin-1 is involved in various cancers, but its expression and role in gastric carcinoma remain unclear. Materials and Methods: Gastric carcinoma and adjacent normal tissues were harvested from 60 patients. Claudin-1 expression was detected by RT-qPCR. The expressions in human gastric carcinoma MKN45, SGC7901 and MKN28 cells and immortalized human gastric epithelium GES-1 cells were determined by RT-qPCR and Western blotting. Claudin-1 was overexpressed in SGC7901 cells by lentiviral transfection, and they were divided into Control (untransfected), normal control (NC) (transfected with lentiviral vector) and Claudin-1 (transfected with Claudin-1 overexpression lentivirus) groups. The proliferation, invasion and migration of gastric carcinoma cells were detected through cell counting kit-8, Transwell and wound healing assays, respectively. The effects of Claudin-1 on the expressions of epithelial-mesenchymal transition (EMT) marker proteins E-cadherin and N-cadherin were detected by Western blotting. Ten 4-week-old male BALB/c nude mice were subcutaneously injected with lentivirus-treated SGC7901 cells to establish the transplanted tumor model, and the effect of overexpression of Claudin-1 was explored. Results: The expression of Claudin-1 in gastric carcinoma tissues was significantly lower than that in adjacent tissues (P&lt;0.05). Overexpression of Claudin-1 significantly inhibited the proliferation, invasion and migration of SGC7901 cells, increased the expression of E-cadherin, and decreased that of N-cadherin (P&lt;0.05). Overexpression of Claudin-1 in the mouse model significantly inhibited the growth of subcutaneous transplanted tumors (P&lt;0.05). Conclusion: Claudin-1 has low expression in gastric carcinoma tissues. Overexpression of Claudin-1 inhibits the proliferation, invasion, migration, and EMT of gastric carcinoma cells, and subcutaneous tumorigenesis in nude mice.

The Effects of P53 in the Globular Heads of the C1q Receptor in Gastric Carcinoma Cell Apoptosis Are Exerted via a Mitochondrial-Dependent Pathway.

The globular heads of the C1q receptor (gC1qR), located in the B cell cytoplasm, perform important roles in many cellular processes. A recent studies reported a major role of mitochondrial apoptosis in several cancers, but there has been no report on gastric carcinoma (GC). In this study, the mechanism by which cell apoptosis is induced by gC1qR in GC was explored. Western blot showed that gC1qR and P53 protein levels were lower in GC tissues than in normal tissues. Cytotoxicity was dynamically increased in gC1qR-overexpressing GC cells compared to the control. CCK8 assay indicated that overexpression of gC1qR induced GC cell apoptosis, increased reactive oxygen species (ROS) production, decreased the mitochondrial transmembrane potential and promoted mitochondrial apoptosis. Moreover, the P53 level increased in response to gC1qR. The viability, migration, and mitochondrial transmembrane potential of GC cells increased in association with decreased levels of ROS and mitochondrial apoptosis in the P53-silenced group. Collectively, our findings indicate that apoptosis of GC cells is enhanced when gC1qR overexpression is induced by P53-mediated mitochondrial apoptosis.

Exosomal circ_0088300 Derived From Cancer-Associated Fibroblasts Acts as a miR-1305 Sponge and Promotes Gastric Carcinoma Cell Tumorigenesis.

Cancer-associated fibroblast (CAF)-derived exosomes play a major role in gastric carcinoma (GC) tumorigenesis. However, the mechanism behind the activity of circular RNAs in CAF-derived exosomes in GC remains unclear. In the present study, we identified differentially expressed circ_0088300 in GC tissues and plasma exosomes. We found that CAFs delivered functional circ_0088300 to GC tumor cells via exosomes and promoted the proliferation, migration and invasion abilities of GC cells. Furthermore, we demonstrated that circ_0088300 packaging into exosomes was driven by KHDRBS3. In addition, we verified that circ_0088300 served as a sponge that directly targeted miR-1305 and promoted GC cell proliferation, migration and invasion. Finally, the JAK/STAT signaling pathway was found to be involved in the circ_0088300/miR-1305 axis, which accelerates GC tumorigenesis. In conclusion, our results indicated a previously unknown regulatory pathway in which exosomal circ_0088300 derived from CAFs acts as a sponge of miR-1305 and promotes GC cell proliferation, migration and invasion; these data identify a potential biomarker and novel therapeutic target for GC in the future.

LncRNA LIFR‑AS1 inhibits gastric carcinoma cell proliferation, migration and invasion by sponging miR‑4698.

The vital functions of long non-coding (lnc)RNAs have been verified in gastric carcinoma (GC). However, as a novel cancer-related lncRNA, the influence of leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) in GC cell biological behaviors remains unreported. The present study explored the biological effects of lncRNA LIFR-AS1 on GC progression. Reverse transcription-quantitative PCR was performed to examine lncRNA LIFR-AS1 expression in GC tissues and cells. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine incorporation, cell wound healing and Transwell invasion assays were used to assess the functions of lncRNA LIFR-AS1 in GC cell proliferation, migration and invasion. Additionally, associations among lncRNA LIFR-AS1, microRNA (miR)-4698 and microtubule-associated tumor suppressor 1 (MTUS1) were investigated via bioinformatics software and a luciferase reporter system. In addition, western blotting was used to examine the expression of MEK and ERK. Decreased lncRNA LIFR-AS1 expression was observed in GC tissues and cells. Upregulated lncRNA LIFR-AS1 inhibited GC cell proliferation, migration and invasion. Upregulated miR-4698 and downregulated MTUS1 were identified in GC tissues and cells. The inhibitory interaction between lncRNA LIFR-AS1 and miR-4698 was confirmed. Additionally, MTUS1 was predicted as a target gene of miR-4698 positively regulated by lncRNA LIFR-AS1. The MEK/ERK pathway was inhibited by lncRNA LIFR-AS1 via regulating MTUS1. These findings revealed the inhibitory functions of lncRNA LIFR-AS1 in GC cell proliferation, migration and invasion. The process was mediated via miR-4698, MTUS1 and the MEK/ERK pathway.

Formononetin exhibits anticancer activity in gastric carcinoma cell and regulating miR-542-5p.

Formononetin exhibits anti-neoplastic activities in specific types of cancers, such as colon carcinoma and breast cancer. Nevertheless, its role in suppressing gastric carcinoma (GC) growth and metastatic-associated phenotypes has not been fully understood. Here, we demonstrated that formononetin decreased the viability of GC cell line SGC-7901 and MGC-803. Furthermore, formononetin suppressed the migration and invasion abilities of GC cells. Consistent with the results in vitro, the anticancer effect of formononetin was verified using xenograft model. The expression of microRNA-542-5p (miR-542-5p), acted as an oncogene in many cancers, was identified to be upregulated in GC. Importantly, miR-542-5p might involve in formononetin exhibits anticancer activity in GC cells. Taken together, these results indicate that formononetin inhibits the growth and aggressiveness of GC cells in vitro and in vivo.

Allicin suppresses growth and metastasis of gastric carcinoma: the key role of microRNA-383-5p-mediated inhibition of ERBB4 signaling.

Allicin is a natural product suppressing the progression of gastric carcinoma (GC). In the current study, the mechanism underlying the anti-GC effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling. Two GC cell lines were treated with allicin and the effects on viability, apoptosis, migration, invasion, and miR-383-5p/ERBB4 activity in the cells were assessed. The interaction between allicin and miR-383-5p was further explored by inhibiting the miR-383-5p level. Allicin suppressed cell viability and induced apoptosis in both GC cell lines. The compound also inhibited migration and invasion of GC cells, which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4. The inhibition of miR-383-5p by specific inhibitor blocked the anti-GC effect of allicin. Our results demonstrated that allicin contributed to the suppressed growth and metastasis potentials in GC cell lines. The effect was accompanied by an increased level of miR-383-5p and subsequent inhibition of ERBB4.

LncRNA IUR Is Downregulated in Gastric Carcinoma and Associated with Poor Survival.

Objective: LncRNA IUR has been recently identified as a key regulator of Bcr-Abl-induced tumorigenesis, while its role in gastric carcinoma (GC) is unknown. This study investigated the involvement of IUR in GC. Materials and Methods: Gene expression levels were measured by performing quantitative polymerase chain reaction. Interactions between IUR and ROCK1 were analyzed by transfection experiments. Cell invasion and migration were analyzed by Transwell assay. Results: In this study, the authors showed that IUR was downregulated in GC. A follow-up study showed that low IUR expression levels predicted poor survival. In GC tissues, ROCK1 was upregulated in GC tissues and inversely correlated with IUR. In GC cells, IUR overexpression mediated the downregulation of ROCK1. ROCK1 overexpression resulted in increased GC cell invasion and migration, while IUR overexpression played an opposite role. Conclusion: IUR is downregulated in GC and inhibits GC cell invasion and migration by downregulating ROCK1.

CircFOXO3 functions as a molecular sponge for miR-143-3p to promote the progression of gastric carcinoma via upregulating USP44.

Gastric carcinoma (GC) ranks fifth in terms of cancer morbidity and third in cancer-related death worldwide and imposes enormous health and economic burdens. The molecular mechanisms underlying GC formation and progression remain unclear. Our aim was to identify the involvement of circular RNA circFOXO3 in GC, and to determine the underlying mechanisms. In this study, we revealed a stimulatory role of circular RNA circFOXO3 in tumor growth in vivo. CircFOXO3 enhanced GC cell proliferation and migration in vitro and promoted tumor growth of GC cells in vivo. Bioinformatic analysis revealed that circFOXO3 might regulate USP44 expression by specifically binding to microRNA (miR)-143-3p. Existence of circFOXO3-miR-143-3p-USP44 axis in GC cells was confirmed by RNA-binding protein immunoprecipitation, luciferase reporter assay, and an RNA pull-down experiments. All the data indicate that circFOXO3 promotes GC cell proliferation and migration by upregulating USP44 expression via targeting of miR-143-3p.

Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma.

The effects of cancer-associated fibroblasts (CAF) on the progression of gastric carcinoma (GC) has recently been demonstrated. However, agents targeting the interaction between CAF and GC cells have not been applied in a clinical setting. Here, we examined if inhibition for Axl receptor tyrosine kinase (AXL) can suppress CAF-induced aggressive phenotype in GC. We investigated the function of CAF-derived growth arrest-specific 6 (GAS6), a major ligand of AXL, on the migration and proliferation of GC cells. The effect of the AXL inhibitor, BGB324, on the CAF-induced aggressive phenotype of GC cells was also investigated. In addition, we performed immunohistochemistry to examine the expression of phosphorylated AXL protein in 175 GC tissues and evaluated its correlation with the prognosis. The qPCR and western blot analysis showed that GAS6 expression was higher in CAF relative to other cells. We found that co-culture with CAF increased the phosphorylation of AXL (P-AXL), differentiation into a mesenchymal-like phenotype, and cell survival in GC cell lines. When the expression of AXL was genetically inhibited in GC cells, the effect of CAF was reduced. BGB324, a small molecule inhibitor of AXL, suppressed the effects of CAF on GC cell lines. In GC tissues, high levels of P-AXL were significantly associated with poor overall survival (P = 0.022). We concluded that CAF are a major source of GAS6 and that GAS6 promotes an aggressiveness through AXL activation in GC. We suggested that an AXL inhibitor may be a novel agent for GC treatment.

Hsa_circ_0001649 restrains gastric carcinoma growth and metastasis by downregulation of miR‐20a

BackgroundGastric carcinoma (GC) is a familiar carcinoma and serious threat to human health. We investigated the efficacy and mechanism of circular RNA hsa_circ_0001649 on the growth, migration, and invasion of GC cells.MethodsmicroRNA (miR)‐20a and hsa_circ_0001649 expression was investigated by RT‐qPCR and was changed by cell transfection. CCK‐8, flow cytometry, and BrdU assays were, respectively, used to investigate the efficacies of hsa_circ_0001649 and miR‐20a on cell viability, apoptosis, and proliferation. Transwell assay was used to investigate the efficacies of hsa_circ_0001649 and miR‐20a on cell migration and invasion. Moreover, the levels of cyclin D1, Bax, cleaved caspase‐3, and signal pathway‐related proteins were investigated by Western blot.ResultsHsa_circ_0001649 was downregulated in GC cells and tissues. Upregulation of hsa_circ_0001649 restrained viability, proliferation, migration, and invasion, while promoted apoptosis. Furthermore, miR‐20a was negatively regulated by hsa_circ_0001649 and miR‐20a overexpression reversed the efficacy of hsa_circ_0001649 upregulation. Finally, upregulation of hsa_circ_0001649 restrained ERK and Wnt/β‐catenin pathways while miR‐20a overexpression reversed these progresses.ConclusionUpregulation of hsa_circ_0001649 restrained GC cell growth and metastasis by downregulating miR‐20a and thereby inactivated ERK and Wnt/β‐catenin pathways.

Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2.

Although Epstein-Barr virus (EBV) is known to encode over 40 different miRNAs of its own, the roles of most EBV miRNAs remain unknown. Disabled homolog 2 (DAB2) is a putative tumor suppressor, but its role in gastric carcinoma (GC), especially in EBV-associated GC, needs to be clarified. Our qRT-PCR and mRNA microarray results showed that DAB2 expression was down-regulated in EBV-positive GC cells compared to EBV-negative cells. Four BART miRNAs that might target DAB2 were predicted, and we found, using a luciferase reporter assay, that miR-BART1-3p directly targeted the 3'-UTR of DAB2. The miR-BART1-3p transfection decreased DAB2 expression at both mRNA and protein levels, while transfection of an inhibitor of miR-BART1-3p, miR-BART1-3p(i), increased DAB2 expression. In addition, miR-BART1-3p as well as siDAB2 increased migration and decreased apoptosis. Meanwhile, miR-BART1-3p(i) or pcDNA3.1-DAB2 transfection decreased migration and increased apoptosis in EBV-infected GC cells. Furthermore, decreased migration by miR-BART1-3p(i) was abrogated by co-transfected siDAB2, while decreased migration by miR-BART1-3p(i) was further suppressed by a co-transfected DAB2 over-expression vector. Our data suggest that miR-BART1-3p plays an important role in the tumorigenesis of EBV-associated GC by directly targeting DAB2.

Dihydroartemisinin inhibits the growth and invasion of gastric cancer cells by regulating cyclin D1-CDK4-Rb signaling

BackgroundDihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has a broad range of biological properties, including antitumor activity. However, the mechanisms by which DHA affects the tumorigenesis of gastric carcinoma (GC) are poorly understood. Material and methodsThe targets of DHA were identified by network pharmacology, and the association of CDK4 with clinicopathological characteristics and prognosis in patients with GC was analyzed by using TCGA data. CCK8, Transwell and flow cytometric analyses, as well as a tumor xenograft model, were used to assess the effects of DHA on the growth and migration of GC cells. qRT-PCR and Western blot analyses were used to determine the effects of DHA on the cyclin D1-CDK4-Rb signaling pathway. ResultsWe identified 13 DHA targets and measured their expression of whichCDK4 expression levels were substantially higher in GC tissues than those in adjacent normal tissues, and high CDK4 expression acted as an independent prognostic factor of poor survival in patients with GC. DHA suppressed cell proliferation, migration and invasion in vitro and in vivo and induced G1 phase cell cycle arrest in a dose-dependent manner by regulating cyclin D1-CDK4-Rb signaling. ConclusionsDHA inhibits the tumorigenesis and invasion of GC by regulating cyclin D1-CDK4-Rb signaling and may provide therapeutic strategies for the treatment of GC.

Identification of GOLM1 as a positively regulator of tumor metastasis by regulating MMP13 in gastric carcinoma.

Metastatic gastric carcinoma (GC) is a typically incurable disease. The progression of anti-metastatic treatment is hampered because the underlying mechanisms regulating the metastasis of GC cell are not well illuminated. Therefore, further elucidation of the molecular mechanism behind the metastatic traits of GC cells is needed for optimizing GC treatment. The levels of GOLM1 and MMP13 in GC cells and tissues were measured by using qPCR assay. The growth of GC cells in vitro was detected using MTS and colony formation assays. The migration and invasion of GC cells was analyzed using wound healing test and Transwell invasion assay. The level of MMP13 in GC cell was measured using immunoblotting and the level of GOLM1 was measured using immunofluorescence staining. The role of GOLM1 on the distant metastasis of GC SGC7910 cell was analyzed using experimental metastasis assay. Transplanted tumor model was constructed to analyze the influence of GOLM1 on GC cell growth in vivo. Here, we report that GOLM1 is over-expressed in GC and knockdown GOLM1 impairs the aggressive phenotypes of GC cell in vitro. Furthermore, downregulation of GOLM1 restrains the tumor growth of GC cell in nude mice. Nevertheless, upregulation of GOLM1 distinctly elevated the growth, migration ability and invasiveness of GC SGC7910 cell. Finally, GOLM1 increases the metastatic phenotypes of GC cell in a MMP13-dependent manner. Altogether, this investigation demonstrates the crucial function of GOLM1 in the progression of GC, which indicating GOLM1 as a potential target for GC treatment.

MiR-135b-5p promotes viability, proliferation, migration and invasion of gastric cancer cells by targeting Krüppel-like factor 4 (KLF4).

IntroductionThe expression of MiR-135b-5p was up-regulated while Krüppel-like factor 4 (KLF4) expression was extremely low in human gastric carcinoma (GC) tissues. This study aimed to explore the role of miR-135b-5p in GC cells and its influence on various cell capacity and viability by targeting KLF4.Material and methodsThe dual-luciferase reporter assay was first performed and the target relationship between miR-135b-5p and KLF4 was confirmed. Then three GC cell lines and the human normal gastric epithelial cell line (GES1) were analyzed for the expression level of miR-135b-5p and KLF4 mRNA by RT-qPCR. The BGC-823 GC cell line was chosen for subsequent assays.ResultsThe expression of miR-135b-5p and KLF4 was manipulated via transfection. The changes of proliferation, invasion, migration, viability, cycle and apoptosis of GC cells were evaluated by MTS, colony formation assay, transwell assay, wound healing assay and flow cytometry assay, respectively. Overexpression of MiR-135b-5p enhanced viability, proliferation, invasion and migration of GC cells, increased cell viability and reduced cell apoptosis. Replenishing of KLF4 functioned oppositely.ConclusionsThe inhibitory effects of ectopic KLF4 could be attenuated by co-transfection of miR-135b-5p. Collective data suggested that miR-135b-5p has a tumor-promoting role in GC cells via downregulating KLF4. Hence, inhibition of miR-135b-5p could be valuable for treatment of gastric cancer.

MiR-29c suppresses cell invasion and migration by directly targeting CDK6 in gastric carcinoma.

Gastric carcinoma (GC) is one common malignant tumor with high morbidity and mortality rates all over the world. Recently, numerous studies have showed that the microRNAs (miRNAs) dysregulation was implicated in GC carcinogenesis. This research aimed to explore the potential associations between miR-29c and cyclin-dependent kinase 6 (CDK6) in GC. GC tissues and corresponding normal tissues were collected from 54 GC patients who underwent surgery at the Second Hospital of Anhui Medical University between 2015 and 2017. We measured the expressions of CDK6 and miR-29c in GC tissues using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We next investigated the functions of miR-29c in GC cells by performing transwell assays. To further determine the correlation between miR-29c and CDK6 in GC cell invasion and migration, the rescue experiments were performed by co-transfecting miR-29c inhibitor and CDK6 siRNA into AGS cells. MiR-29c expressions were significantly declined in GC tissues and cells. Additionally, functional assays showed that the miR-29c over-expression suppressed the invasion and migration capacities of GC cells. According to TargetScan and dual-luciferase reporter assays, CDK6 was identified as a new miR-29c target. Moreover, the knockout of CDK6 had similar effects as the miR-29c over-expression in GC cells. The current research indicated that miR-29c over-expression could inhibit tumor behaviors in GC partially via down-regulating CDK6. We revealed that miR-29c down-regulated in GC tissues and cells. MiR-29c over-expression effectively suppressed the GC cell invasion and migration. Moreover, CDK6 was identified as a direct functional target of miR-29c in GC. The current study provides new insights for the GC treatment and suggests that miR-29c/CDK6 axis is a therapeutic candidate target for GC patients.