scholarly journals miR-1273h-5p Suppresses the Penetration and Pervasion of Gastric Cancer Cells via Suppressing CXCL12 Expression

2021 ◽  
Author(s):  
Yi-Chen Wang ◽  
Song Lu ◽  
Xiao-Jiang Zhou ◽  
Li Yang ◽  
ping liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Biological Function ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Gastric Cancer Cells ◽  
Cxcl12 Expression ◽  
Tissue Samples ◽  
Normal Tissues

Abstract Purpose: microRNAs (miRNAs), which may function as oncogenes or tumor suppressors, have been verified in the development of breast carcinoma, melanoma, and some other tumors. The dysregulated miR-1273h-5p in tissue samples of gastric cancer (GC) may be involved in the progression of GC. The aim of this study was to verify the biological function of miR-1273h-5p in GC progression.Method: The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected by microarrays, and polymerase chain reaction (PCR) analysis was used for miR-1273h-5p and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA expressions. The effect of miR-1273h-5p on cell proliferation and apoptosis was evaluated by CCK-8 assay and flow cytometry; cell migration and invasion were observed by using the transwell method. In addition, protein levels were determined by Western blot. SGC-7901 cell transfected gene sequences were injected into BALB/c-nu mice to establish a xenograft model in order to validate the biological function of miR-1273h-5p in vivo.Results: Compared to tumor-adjacent normal tissue and GES-1 cells, miR-1273h-5p was significantly down-regulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant up-regulation of CXCL12 was observed when the miR-1273h-5p was down-regulated in GC cells. Additionally, tumor tissues were collected from mice after 21 days of feeding, revealing that miR-1273h-5p significantly reduces tumor volume and tumor weight. Conclusions: miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3'-UTR, thus can be used as a potential diagnostic and a novel therapeutic target for GC in clinical practice.

scholarly journals MicroRNA-99a promotes cell proliferation, migration and invasion in gastric cancer by modulating c-Src

2019 ◽  
Author(s):  
Yue Pan ◽  
Weixing Chen ◽  
Xin Yuan ◽  
Hongpeng Lu ◽  
Lei Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Normal Tissues ◽  
Qrt Pcr

Abstract Background: Recent studies have shown that microRNA-99a(miR-99a)plays a key role in the development of virious malignancies; however, its relationship with gastric cancer remains unclear. In this study, we investigated the functions and potential mechanisms of miR-99a in gastric cancer. Methods: Real-time qRT-PCR was used to assess the expression levels of miR-99a in gastric cancer tissue samples and cell lines compared to their matched adjacent normal tissues and a normal gastric mucosa epithelial cell line, respectively. SGC-7901 cells were transfected with miR-99a mimics and negative controls to determine the effects of miR-99a overexpression on cell proliferation, cell cycle transition, migration and invasion of gastric cancer cells in vitro . The role of miR-99a in endogenous c-Src expression in gastric cancer cells was also investigated by qRT-PCR and Western blotting. Results: Our results showed a significant increase in miR-99a expression in both gastric cancer tissues and cells compared to normal tissues and cells. Overexpression of miR-99a significantly promoted the cell proliferation, migration and invasion of gastric cancer cells compared to normal cells, with a concurrent increase in the S+G2 phases of the cell cycle. Further investigations found that miR-99a overexpression led to significant upregulation of endogenous c-Src. Conclusion: Taken together, our findings suggest that miR-99a may act as a tumour promoter in the pathogenesis of gastric cancer by indirectly modulating c-Src expression.

Magnesium-dependent Phosphatase (MDP) 1 is a Potential Suppressor of Gastric Cancer

2019 ◽  
Vol 19 (10) ◽  
pp. 817-827
Author(s):  
Jianbo Zhu ◽  
Lijuan Deng ◽  
Baozhen Chen ◽  
Wenqing Huang ◽  
Xiandong Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Cell Proliferation ◽  
Protein C ◽  
Biological Function ◽  
Prognostic Markers ◽  
Biological Effects ◽  
Signal Transducer ◽  
Gastric Cancer Cells ◽  
Transcription 3

Background:Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.Methods:We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.Results:A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.Conclusion:These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.

scholarly journals Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1820
Author(s):  
Chengcheng Hao ◽  
Yuxin Cui ◽  
Jane Lane ◽  
Shuqin Jia ◽  
Jiafu Ji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Prognostic Value ◽  
Splice Variants ◽  
Tnm Staging ◽  
Migration And Invasion ◽  
Ros Production ◽  
Gastric Cancer Cells ◽  
Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

Silencing of hsa_circ_0000515 Inhibits Proliferation, Migration and Invasion of Gastric Cancer Cells by Sponging miR-615-5p In Vitro

2021 ◽  
Vol 11 (8) ◽  
pp. 1466-1476
Author(s):  
Xuli Wang ◽  
Aiping Wang
Keyword(s):  
Gastric Cancer ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Gastric Cancer Cells ◽  
Novel Target

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. This study investigates the role of circRNA hsa_circ_0000515 in gastric cancer (GC) cells and the underlying mechanism associated with microRNA-615-5p (miR-615-5p). qRT-PCR analysis showed the upregulation of hsa_circ_0000515 and downregulation of miR-615-5p in GC cell lines. Loss-of-function experiments indicated that suppression of hsa_circ_0000515 inhibited cell proliferation, migration, and invasion. Dual-luciferase reporter assay highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-615-5p. Furthermore, hsa_circ_0000515 could interact with splicing factors and bind miR-615-5p to regulate progression of GC cells. Deficiency of miR-615-5p reverses the inhibitory roles of si-hsa_circ_0000515 on the proliferation, migration, and invasion of GC cells. The findings highlighted the promising uses of hsa_circ_0000515 as a likely novel target for gastric cancer treatment.

scholarly journals LINC00152 down-regulated miR-193a-3p to enhance MCL1 expression and promote gastric cancer cells proliferation

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Yong Huang ◽  
Hui Luo ◽  
Fang Li ◽  
Yun’e Yang ◽  
Guangsheng Ou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Xenograft Model ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Mouse Xenograft Model ◽  
Vitro Effect

The present work aimed to probe into the effect of long non-coding RNA (lncRNA) LINC00152 on gastric cancer (GC) cells proliferation by regulating miR-193a-3p and its target gene MCL1. Transfected si-LINC00152 was used to down-regulate LINC00152, and cells proliferation was measured by the cell counting kit-8 (CCK-8) assay. Cell apoptosis and cell cycle were analyzed by flow cytometry (FCM). Besides, we also detected the potential functional effects of differential expression of LINC00152 in vivo using nude mouse xenograft model. We overexpressed and downexpressed miR-193a-3p to study the in vitro effect of miR-193a-3p on GC cells proliferation and vitality. And MCL1 was silenced by shRNA to investigate the effect of MCL1 on proliferation of GC cells. In this research, LINC00152 was proven to have a higher expression level in GC tissues than in the adjacent normal tissues. GC cells proliferation was inhibited after LINC00152 was down-regulated. LINC00152 inhibited the expression of miR-193a-3p, which negatively regulated MCL1. In addition, GC cells proliferation was inhibited by cell transfection with shRNA-MCL1, and enhanced by transfection with miR-193a-3p mimics. Our study suggested that LINC00152 was overexpressed in GC tissues, and it down-regulated miR-193a-3p to enhance MCL1 expression thereby promoting GC cells proliferation.

scholarly journals The pseudogene-derived long non-coding RNA SFTA1P suppresses cell proliferation, migration, and invasion in gastric cancer

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Hongwei Ma ◽  
Tianshi Ma ◽  
Miao Chen ◽  
Zigui Zou ◽  
Zhihong Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Human Cancer ◽  
Current Evidence ◽  
Migration And Invasion ◽  
Strongly Correlated ◽  
Normal Tissues ◽  
Advanced Tumor ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Pseudogenes were once regarded as transcriptionally inactive and without specific molecular function. However, current evidence shows that pseudogene-derived long non-coding RNAs (lncRNAs) may be crucial regulators of human cancer development, including gastric cancer (GC). In the present study, we report that a pseudogene-derived lncRNA named surfactant associated 1, pseudogene (SFTA1P), which is 693-nt long, was significantly down-regulated in GC tissues compared with that in the adjacent normal tissues. In addition, decreased SFTA1P expression was strongly correlated with advanced tumor lymph node metastasis (TNM) stage, larger tumor size, lymphatic metastasis, and poor prognosis of patients with GC. Moreover, gain-of-function experiments revealed that the overexpression of SFTA1P inhibits cell proliferation, migration, and invasion, thus verifying the tumor inhibitory role of SFTA1P in GC. Furthermore, we investigated the potential action mechanism of SFTA1P. Our results showed that down-regulation of SFTA1P may be associated with decreased TP53 expression. In summary, our work suggests that the pseudogene-derived lncRNA SFTA1P functions as a tumor suppressor in GC and thus may act as a potential diagnostic and therapeutic target of GC.

scholarly journals MiR-496 Inhibits the Proliferation Through Targeting LYN and AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Author(s):  
Rui Su ◽  
Enhong Zhao ◽  
Jun Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Mtor Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Ags Cells

Abstract MiRNA operates as a tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis and metabolic process. In the present research, we investigated the effect and mechanism of miR496 in human gastric cancer cells. Cell proliferation was measured by CCK8 and clonogenic assay. Transwell test was performed to detect cell migration and invasion. Flow cytometry analysis was used to evaluate cell apoptosis. Bioinformatics software targetscan was used for the screening of miR-496’s target gene. MiR-496 was down regulated in three gastric cancer cell lines, SGC-790, AGS and MKN45 compared with normal gastric epithelial cell line GES-1. MiR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 h and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. In addition, miR-496 mimics induced the apoptosis through up regulating the levels of Bax and Active Caspase3 and down regulating the levels of Bcl-2 and Total Caspase3. Bioinformatics analysis showed that there was a binding site between miR-496 and LYN kinase (LYN). MiR-496 mimics could inhibit the expression of LYN in AGS cells. The overexpression of LYN blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496 in gastric cancer cells. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment of gastric cancer.

scholarly journals Chrysophanol Inhibits the Progression of Gastric Cancer by Activating NLRP3

2021 ◽  
Author(s):  
Hou Binfen ◽  
Li Zhao ◽  
Min Deng
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Antitumor Effects ◽  
Ags Cells ◽  
Anti Cancer ◽  
Colony Forming Assay

Abstract AimGastric cancer is one of the most common malignant tumors.Chrysophanol has been reported to have antitumor effects on a variety of cancers, but the role of chrysophanol in gastric cancer remains unclear. The aim of this study was to investigate the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of gastric cancer cells.MethodsMKN 28 and AGS cells were treatde with different concentrations of chrysophanol, then cell proliferation, migration,invasion and pyroptosis were decteed by CCK-8, Colony-forming assay, Wound Healing assay, Transwell and flow cytometry, respectively.Subsequently, NLRP3 siRNA was transfected into MKN 28 cells, cell proliferation pyroptosis, migration and invasion were reassessed in these transfected cells. The expression of caspase-1 and IL-1β in the downstream of NLRP3 was detected by qRT PCR and Western blot.ResultsChrysophanol significantly inhibited the proliferation of GC cells, promoted pyroptosis, inhibited cell migration and invasion, and up-regulated the expression level of NLRP3 inflammasome in GC cells. Silencing NLRP3 inhibited the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of MKN 28 cells. Chrysophanol plays an anti-cancer role through high expression of NLRP3.CoclusionsChrysophanol can inhibit the proliferation, migration and invasion of gastric cancer cells by regulating NLRP3, promote the death of gastric cancer cells, and play an anti-tumor role,which is a clinical strategy with great potential for the treatment of gastric cancer.

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