scholarly journals Upregulation of long noncoding RNA SNHG1 indicates a poor prognosis in patients with gastric cancer

2020 ◽  
Vol 18 ◽  
pp. 205873922094614
Author(s):  
Hua-Li Zhu ◽  
Jing Zou
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Expression Levels

It is indicated that the dysregulation of long noncoding RNAs (lncRNAs) is implicated in cancer progression. However, the clinical significance of lncRNA small nucleolar RNA host gene 1 (SNHG1) in gastric cancer remains elusive. The expression levels of SNHGs and the association of SNHG1/10/11 with the clinical characteristics in patients with gastric cancer were analyzed by The Cancer Genome Atlas RNA-seq data. A Cox proportional hazard regression model was used to evaluate the association of SNHG1/10/11 expression with the clinical outcomes in patients with gastric cancer. It was demonstrated that SNHG1/10/11 expression levels were dramatically elevated in gastric cancer tissue samples as compared with the adjacent normal tissues. Increased expression of SNHG1 had no correlation with the clinicopathological parameters, but acted as an independent prognostic factor of poor survival (hazard ration (HR) = 0.590, 95% confidence interval (CI) = 0.399–0.872, P = 0.008) and tumor recurrence (HR = 2.457, 95% CI = 1.442–4.186, P = 0.001) in patients with gastric cancer. In addition, knockdown of SNHG1 in vitro inhibited the proliferation and invasion of gastric cancer cells. Our findings showed that the upregulation of lncRNA SNHG1 indicated a poor prognosis in patients with gastric cancer and might offer a promising therapeutic target for gastric cancer.

Identification of a novel molecule target for the diagnosis, prediction, and treatment of hepatic metastasis of gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 53-53
Author(s):  
Mitsuro Kanda ◽  
Haruyoshi Tanaka ◽  
Takashi Miwa ◽  
Daisuke Kobayashi ◽  
Chie Tanaka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Hepatic Metastasis ◽  
Clinicopathological Parameters ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Hepatic Recurrence ◽  
Cancer Tissues

53 Background: Hepatic metastasis of gastric cancer has become a growing issue, because effective treatment and specific biomarkers are not available. The aim of this study was to identify a molecule mediating hepatic metastasis, which serves as a diagnostic marker, and to determine its potential as a therapeutic target. Methods: Stable knockdown gastric cancer cells were established using genome editing technique and cell activities were compared to control cells in vitro and in vivo. Tissue expression levels of the candidate molecule were evaluated in 300 patients with gastric cancer and correlated to clinicopathological parameters including patterns of metastasis and recurrences. Results: Global expression analysis revealed that synaptotagmin VII (SYT7) was overexpressed in gastric cancer tissues with hepatic metastasis. Gastric cancer cell lines differentially expressed high levels of SYT7 that positively correlated with those of SNAI1 and TGFB3, and inversely with RGS2. Stable knockout of SYT7 inhibited the proliferation of gastric cancer cells, indicated by increased apoptosis, and decreased cell migration, invasion, and adhesion abilities. The tumorigenicity of SYT7 knockout cells was moderately reduced in a mouse subcutaneous model and more strikingly decreased in a hepatic metastasis model. The protein expression levels of BCL2 and HIF1A were decreased in tumors formed by SYT7 knockout cells, and SYT7 levels in primary gastric cancer tissues were significantly associated with hepatic recurrence, metastasis, and adverse prognosis. Conclusions: SYT7 serves as a target for treating hepatic metastasis of gastric cancer as well as a diagnostic tool.

scholarly journals Overexpression of TC2N is associated with poor prognosis in gastric cancer

2020 ◽  
Author(s):  
Jianbo Xu ◽  
Xinde Ou ◽  
Jin Li ◽  
Qinbo Cai ◽  
Kaiyu Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Gastric Epithelium ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Term Survival

Abstract Background Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of TC2N expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of TC2N level in GC. Methods We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze TC2N expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA). TC2N expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction(RT-PCR)and Western blot(WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center. In vitro proliferation, migration and invasion assays were used to evaluate the effect of TC2N on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with TC2N. Results The mRNA and protein expression of TC2N in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell. In vitro assays suggested that TC2N facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of TC2N on the transcriptome and a strong interaction with tumor associated genes. We also found that TC2N was an independent prognostic factor for long-term survival in GC patients and its high expression was significantly associated with poor overall survival and recurrence-free survival. Conclusions Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.

scholarly journals HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Marta Smolińska ◽  
Dariusz Grzanka ◽  
Paulina Antosik ◽  
Anna Kasperska ◽  
Izabela Neska-Długosz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Statistical Significance ◽  
Expression Patterns ◽  
Clinical Information ◽  
Tissue Microarrays ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Satb1 Expression

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.

scholarly journals Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1088 ◽  
Author(s):  
I-Han Wang ◽  
Tzu-Ting Huang ◽  
Ji-Lin Chen ◽  
Li-Wei Chu ◽  
Yueh-Hsin Ping ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Nuclear Translocation ◽  
Mevalonate Pathway ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.

scholarly journals miR-125b Suppresses Proliferation and Invasion by Targeting MCL1 in Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shihua Wu ◽  
Feng Liu ◽  
Liming Xie ◽  
Yaling Peng ◽  
Xiaoyuan Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Clinical Stage ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

Understanding the molecular mechanisms underlying gastric cancer progression contributes to the development of novel targeted therapies. In this study, we found that the expression levels of miR-125b were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Additionally, miR-125b could independently predict OS and DFS in gastric cancer. We further found that upregulation of miR-125b inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. miR-125b elicits these responses by directly targeting MCL1 (myeloid cell leukemia 1), which results in a marked reduction in MCL1 expression. Transfection of miR-125b sensitizes gastric cancer cells to 5-FU-induced apoptosis. By understanding the function and molecular mechanisms of miR-125b in gastric cancer, we may learn that miR-125b has the therapeutic potential to suppress gastric cancer progression and increase drug sensitivity to gastric cancer.

scholarly journals Long Noncoding RNA EGFR-AS1 Promotes Cell Proliferation by Increasing EGFR mRNA Stability in Gastric Cancer

2018 ◽  
Vol 49 (1) ◽  
pp. 322-334 ◽  
Author(s):  
Jiaojiao Hu ◽  
Yingying Qian ◽  
Lipan Peng ◽  
Ling Ma ◽  
Tianzhu Qiu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Mrna Stability ◽  
Noncoding Rna ◽  
Synthesis Inhibitor ◽  
Egfr Expression ◽  
Gastric Cancer Progression

Background/Aims: LncRNA EGFR-AS1 is an antisense transcript of EGFR, which plays a key role in gastric cancer progression. This study was aimed to explore the effects of lncRNA EGFR-AS1 on GC and the underling mechanisms. Methods: The silencing of EGFR-AS1 expression was performed by using EGFR-AS1 shRNA lentivirus in MGC803 and SGC-7901 GC cell. The levels of lncRNA EGFR-AS1 and EGFR were detected by qPCR and western blot. Cell proliferation was assessed by CCK-8, EdU, and colony formation assays. The EGFR mRNA stability was explored by using RNA synthesis inhibitor α-amanitin. Results: In our study, EGFR-AS1 significantly up-regulated in GC tissues and correlated with tumor size. And the expression of EGFR-AS1 positively correlated with EGFR in tissues. Moreover, knock-down of EGFR-AS1 inhibited the proliferation of GC cells via suppressing EGFR-dependent PI3K/AKT pathway in vitro and in vivo. Mechanismly, depletion of EGFR-AS1 was found to decrease EGFR expression by reduction of EGFR mRNA stability. Conclusion: Our findings suggested that EGFR-AS1 might have an oncogenic effect on GC and serve as a potential target of GC.

EDD1 predicts prognosis and regulates gastric cancer growth in vitro and in vivo via miR-22

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Min Yang ◽  
Nan Jiang ◽  
Qi-wei Cao ◽  
Qing Sun
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Patient Survival ◽  
Underlying Mechanism ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Abstract Gastric cancer is the most common digestive malignant tumor worldwild. EDD1 was reported to be frequently amplified in several tumors and played an important role in the tumorigenesis process. However, the biological role and potential mechanism of EDD1 in gastric cancer remains poorly understood. In this study, we are aim to investigate the effect of EDD1 on gastric cancer progression and to explore the underlying mechanism. The results showed the significant up-regulation of EDD1 in -gastric cancer cell tissues and lines. The expression level of EDD1 was also positively associated with advanced clinical stages and predicted poor overall patient survival and poor disease-free patient survival. Besides, EDD1 knockdown markedly inhibited cell viability, colony formation, and suppressed tumor growth. Opposite results were obtained in gastric cancer cells with EDD1 overexpression. EDD1 knockdown was also found to induce gastric cancer cells apoptosis. Further investigation indicated that the oncogenic role of EDD1 in regulating gastric cancer cells growth and apoptosis was related to its PABC domain and directly through targeting miR-22, which was significantly down-regulated in gastric cancer tissues. Totally, our study suggests that EDD1 plays an oncogenic role in gastric cancer and may be a potential therapeutic target for gastric cancer.

scholarly journals LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhifu Gui ◽  
Zhenguo Zhao ◽  
Qi Sun ◽  
Guoyi Shao ◽  
Jianming Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells ◽  
Poor Overall Survival

Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.

scholarly journals Comprehensive Genomic Characterization Analysis Identifies an Oncogenic Pseudogene RP11-3543B.1 in Human Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xin Chen ◽  
Zhenyao Chen ◽  
Hao Wu ◽  
Xianghua Liu ◽  
Fengqi Nie ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Expression Profiling ◽  
The Cancer Genome Atlas ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Altered Expression ◽  
Genomic Characterization

Background: Gastrointestinal Cancer (GICs) is the most common group of malignancies, and many of its types are the leading causes of cancer related death worldwide. Pseudogenes have been revealed to have critical regulatory roles in human cancers. The objective of this study is to comprehensive characterize the pseudogenes expression profiling and identify key pseudogenes in the development of gastric cancer (GC).Methods: The pseudogenes expression profiling was analyzed in six types of GICs cancer from The Cancer Genome Atlas RNA-seq data to identify GICs cancer related pseudogenes. Meanwhile, the genomic characterization including somatic alterations of pseudogenes was analyzed. Then, CCK8 and colony formation assays were performed to evaluate the biological function of RP11-3543B.1 and miR-145 in gastric cancer cells. The mechanisms of pseudogene RP11-3543B.1 in GC cells were explored via using bioinformatics analysis, next generation sequencing and lucifarese reporter assay.Results: We identified a great number of pseudogenes with significantly altered expression in GICs, and some of these pseudogenes expressed differently among the six cancer types. The amplification or deletion in the pseudogenes-containing loci involved in the alterations of pseudogenes expression in GICs. Among these altered pseudogenes, RP11-3543B.1 is significantly upregulated in gastric cancer. Down-regulation of RP11-3543B.1 expression impaired GC cells proliferation both in vitro and in vivo. RP11-3543B.1 exerts oncogene function via targeting miR-145-5p to regulate MAPK4 expression in gastric cancer cells.Conclusion: Our study reveals the potential of pseudogenes expression as a new paradigm for investigating GI cancer tumorigenesis and discovering prognostic biomarkers for patients.

scholarly journals S100P is a molecular determinant of E-cadherin function in gastric cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Patrícia Carneiro ◽  
Ana Margarida Moreira ◽  
Joana Figueiredo ◽  
Rita Barros ◽  
Patrícia Oliveira ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Data Mining Approach ◽  
Molecular Determinant ◽  
Gastric Cancer Patients ◽  
And Function ◽  
E Cadherin

Abstract Background E-cadherin has been awarded a key role in the aetiology of both sporadic and hereditary forms of gastric cancer. In this study, we aimed to identify molecular interactors that influence the expression and function of E-cadherin associated to cancer. Methods A data mining approach was used to predict stomach-specific candidate genes, uncovering S100P as a key candidate. The role of S100P was evaluated through in vitro functional assays and its expression was studied in a gastric cancer tissue microarray (TMA). Results S100P was found to contribute to a cancer pathway dependent on the context of E-cadherin function. In particular, we demonstrated that S100P acts as an E-cadherin positive regulator in a wild-type E-cadherin context, and its inhibition results in decreased E-cadherin expression and function. In contrast, S100P is likely to be a pro-survival factor in gastric cancer cells with loss of functional E-cadherin, contributing to an oncogenic molecular program. Moreover, expression analysis in a gastric cancer TMA revealed that S100P expression impacts negatively among patients bearing Ecad− tumours, despite not being significantly associated with overall survival on its own. Conclusions We propose that S100P has a dual role in gastric cancer, acting as an oncogenic factor in the context of E-cadherin loss and as a tumour suppressor in a functional E-cadherin setting. The discovery of antagonist effects of S100P in different E-cadherin contexts will aid in the stratification of gastric cancer patients who may benefit from S100P-targeted therapies. Graphical abstract

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