scholarly journals HOXD-AS1 confers cisplatin resistance in gastric cancer through epigenetically silencing PDCD4 via recruiting EZH2

Open Biology ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 190068 ◽  
Author(s):  
Yafei Ye ◽  
Shengnan Yang ◽  
Yanping Han ◽  
Jingjing Sun ◽  
Lijuan Xv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Antisense Rna ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cells ◽  
Hoxd Cluster ◽  
Non Coding Rnas ◽  
Cancer Tissues ◽  
Cancer Chemoresistance

Increasing evidence suggests that dysregulation of long non-coding RNAs (lncRNAs) is implicated in chemoresistance in cancers. However, the function and molecular mechanisms of lncRNAs in gastric cancer chemoresistance are still not well understood. In this study, we aimed to investigate the functional role and the underlying molecular mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in cisplatin (DDP) resistance in gastric cancer. Our results revealed that HOXD-AS1 was upregulated in DDP-resistant gastric cancer tissues and cells. Patients with gastric cancer with high HOXD-AS1 expression levels had a poor prognosis. Knockdown of HOXD-AS1 facilitated the sensitivity of DDP-resistant gastric cancer cells to DDP. Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing counteracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells. In summary, HOXD-AS1 led to DDP resistance in gastric cancer by epigenetically suppressing PDCD4 expression, providing a novel therapeutic strategy for patients with gastric cancer with chemoresistance.

scholarly journals The circBVES Acts as a Sponge of miR-145-5p to Promote Gastric Cancer Glycolysis and Progression Through Regulating HMGB3 Expression

2020 ◽  
Author(s):  
Lu Jin ◽  
Zhiwei He ◽  
Changhao Zhu ◽  
Guoliang Xiao ◽  
Xianjin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Gastric Cancer Cells ◽  
Repressive Effect ◽  
Cancer Tissues

Abstract Background: CircRNA is a new type of non-coding RNA that has attracted much attention for involvement in the development and progression of various human diseases, especially cancer. The most reported role of circRNA in many tumors is ‘MiRNA sponge’. We aimed to investigate the role of circBVES in the proliferation and glycolysis of gastric cancer cells and its molecular mechanisms.Methods: In this study, higher CircBVES expression in gastric cancer tissues was detected by RNA sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of CircBVES in gastric cancer tissues, and the relationship between the expression of CircBVES and prognosis was further analyzed. Then, the effects of CircBVES on the growth and glycolysis of gastric cancer cells were investigated through in vitro and in vivo functional experiments. The interaction between CircBVES and miR-145-5p was detected by bioinformatics analysis, luciferase activity assay and RNA immunoprecipitation.Results: We found that the expression of CircBVES in gastric cancer tissues was evidently up-regulated, and its level was closely correlated with the prognosis of patients with gastric cancer. Inhibition of CircBVES decreased cell proliferation and glycolysis in vitro. Low expression of CircBVES inhibited tumor growth in vivo. Mechanism analysis showed that CircBVES may serve as a competitive endogenous RNA of miR-145-5p to reduce the expression of miR-145-5p in gastric cancer cells, and relieve the repressive effect of miR-145-5p on target genes HMGB3 and cycle-related proteins CCNE1 and CDK2.Conclusions: Our results suggest that CircAGFG1 may promote the progress of gastric cancer through the CircBVES / miR-145-5p / HMGB3 axis, providing a new target for the treatment of gastric cancer cells.

scholarly journals XEDAR inhibits the proliferation and induces apoptosis of gastric cancer cells by regulating JNK signaling pathway

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Lihong Yang ◽  
Xiaojun Huang ◽  
Wei Wang ◽  
Tao Jiang ◽  
Feifei Ding
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cells ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis ◽  
Cancer Tissues

Abstract X-linked ectodermal dysplasia receptor (XEDAR) has been widely studied in epidermal morphogenesis, but few studies have been conducted on tumorigenesis and development, including gastric cancer. In the present research, we aimed to investigate the effect of XEDAR on gastric cancer and further explore the molecular mechanisms involved. The differential expression of XEDAR in 90 tissue specimens (30 gastric cancer tissues, 30 adjacent tissues and 30 normal tissues) was detected by real-time PCR (RT-PCR) and Western blot. Cell proliferation and apoptosis were explored using MTT and Annexin-V/propidium iodide (PI) assays, respectively. The results revealed that the expression of XEDAR was decreased in gastric cancer tissues and in gastric cancer cell lines, and its expression is regulated by p53 in BGC-823 cells. Furthermore, overexpression of XEDAR inhibited cell proliferation and induced apoptosis in BGC-823 cells. XEDAR moreover inhibited proliferation and induced apoptosis in gastric cancer cells by regulating the JNK signaling pathway. Collectively, the results of the present study suggested that XEDAR inhibits cell proliferation and induces apoptosis by participating in p53-mediated signaling pathway and inhibiting the downstream JNK signaling pathway in gastric cancer.

Long non-coding RNA LINC00982 up-regulates CTSF expression to inhibit gastric cancer progression via the transcription factor HEY1

2020 ◽  
Author(s):  
Lei Zheng ◽  
Junli Cao ◽  
Lijie Liu ◽  
Hongmei Xu ◽  
Lanlan Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Non Coding Rna ◽  
Cancer Tissues ◽  
Long Non Coding Rna

Upregulating the expression of long non-coding RNA LINC00982 controlled cell proliferation in gastric cancer, but the regulatory molecular mechanisms are yet to be expounded. We here aimed to elaborate how LINC00982 regulated the malignancy of gastric cancer cells. RT-qPCR and Western blot analysis were used to detect the expression of LINC00982 and CTSF in gastric cancer tissues and cells. Modulatory effect of LINC00982 on gastric cancer cells was assessed by CCK-8, colony formation, Transwell migration and invasion assays. The relationship between LINC00982, HEY1 and CTSF was examined by RIP, luciferase assay, and ChIP, and their interaction in the regulation of gastric cancer cellular functions was analyzed by performing gain-of-function and rescue assays. The nude mouse model of tumor formation was developed to examine the effects of LINC00982 on tumorigenesis. LINC00982 was lowly expressed in gastric cancer tissues, while its overexpression impaired the proliferative, migratory and invasive properties of gastric cancer cells. Furthermore, LINC00982 could bind to transcription factor HEY1 and inhibited its expression. Through blocking the binding of HEY1 to CTSF promoter. LINC00982 promoted the expression of CTSF. Overexpression of HEY1 or inhibition of CTSF could reverse the anti-tumor effects of LINC00982 on gastric cancer, which were further demonstrated in vivo. Taken together, LINC00982 acted as a tumor suppressor in gastric cancer, which is therefore suggested to be a potential anti-tumor target for gastric cancer.

Effects and Mechanisms of Anlotinib and Dihydroartemisinin Combination Therapy in Ameliorating Malignant Biological Behavior of Gastric Cancer Cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Qiong Luo ◽  
Suyun Zhang ◽  
Donghuan Zhang ◽  
Rui Feng ◽  
Nan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Chorioallantoic Membrane ◽  
Cell Counting ◽  
Biological Behavior ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
Apoptosis Related Protein ◽  
And Migration

Background: Gastric cancer(GC) is currently one of the major malignancies that threatens human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert anti-tumor effects. However, the function in gastric cancer is incompletely understood. Objective: The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Method: Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the cell counting kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken chorioallantoic membrane (CAM) assays. proliferation-associated protein (Ki67), apoptosis-related protein (Bcl-2), and vascular endothelial growth factor A (VEGF-A) were quantified by Western bloting. Results: The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with in control and either drug alone. Conclusion: The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.

scholarly journals MicroRNA-154 Inhibits the Growth and Invasion of Gastric Cancer Cells by Targeting DIXDC1/WNT Signaling

2018 ◽  
Vol 26 (6) ◽  
pp. 847-856 ◽  
Author(s):  
Jifu Song ◽  
Zhibin Guan ◽  
Maojiang Li ◽  
Sha Sha ◽  
Chao Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Inverse Correlation ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Cancer Cell Growth ◽  
Cancer Tissues

MicroRNAs (miRNAs) have emerged as pivotal regulators of the development and progression of gastric cancer. Studies have shown that miR-154 is a novel cancer-associated miRNA involved in various cancers. However, the role of miR-154 in gastric cancer remains unknown. Here we aimed to investigate the biological function and the potential molecular mechanism of miR-154 in gastric cancer. We found that miR-154 was significantly downregulated in gastric cancer tissues and cell lines. The overexpression of miR-154 significantly repressed the growth and invasion of gastric cancer cells. Bioinformatics analysis and Dual-Luciferase Reporter Assay data showed that miR-154 directly targeted the 3′-untranslated region of Dishevelled‐Axin domain containing 1 (DIXDC1). Real-time quantitative polymerase chain reaction and Western blot analyses showed that miR-154 overexpression inhibited DIXDC1 expression. An inverse correlation of miR-154 and DIXDC1 was also demonstrated in gastric cancer specimens. Overexpression of miR-154 also significantly suppressed the activation of WNT signaling. Moreover, restoration of DIXDC1 expression significantly reversed the inhibitory effect of miR-154 overexpression on the cell proliferation, invasion, and WNT signaling in gastric cancer cells. Overall, these results suggest that miR-154 inhibits gastric cancer cell growth and invasion by targeting DIXDC1 and could serve as a potential therapeutic target for the treatment of gastric cancer.

scholarly journals SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qing Li ◽  
Dachuan Zhang ◽  
Hui Wang ◽  
Jun Xie ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Gastric Cancer Cells ◽  
Anion Transporter ◽  
Transporter Family ◽  
Cancer Tissues ◽  
Development Of Gastric Cancer

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.

scholarly journals GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hong Chen ◽  
Lu Xu ◽  
Zhi-li Shan ◽  
Shu Chen ◽  
Hao Hu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Western Blot ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Abstract Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.

scholarly journals MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

2017 ◽  
Vol 25 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Chunsheng Li ◽  
Jingrong Dong ◽  
Zhenqi Han ◽  
Kai Zhang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

Accurate detection of matrix metalloproteinase-2 activity in clinical gastric cancer tissues using a fluorescent probe

2019 ◽  
Vol 11 (11) ◽  
pp. 1516-1521 ◽  
Author(s):  
Fujuan Luan ◽  
Zuhong Yu ◽  
Ling Yin ◽  
Xia Leng ◽  
Yuxue Shi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Fluorescent Probe ◽  
Matrix Metalloproteinase 2 ◽  
Gastric Cancer Cells ◽  
New Approach ◽  
Accurate Detection ◽  
Cancer Tissues

A new approach for specific and accurate detection of the activated MMP-2 both in gastric cancer cells and clinical tissues using a fluorescent probe is described here.

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