scholarly journals Global Analyses of Expressed Piwi-Interacting RNAs in Gastric Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7656
Author(s):  
Tatiana Vinasco-Sandoval ◽  
Fabiano Cordeiro Moreira ◽  
Amanda F. Vidal ◽  
Pablo Pinto ◽  
André M. Ribeiro-dos-Santos ◽  
...  

Gastric cancer (GC) represents a notable amount of morbidity and mortality worldwide. Understanding the molecular basis of CG will offer insight into its pathogenesis in an attempt to identify new molecular biomarkers to early diagnose this disease. Therefore, studies involving small non-coding RNAs have been widely explored. Among these, PIWI-interacting RNAs (piRNAs) are an emergent class that can play important roles in carcinogenesis. In this study, small-RNA sequencing was used to identify the global piRNAs expression profile (piRNome) of gastric cancer patients. We found 698 piRNAs in gastric tissues, 14 of which were differentially expressed (DE) between gastric cancer (GC), adjacent to gastric cancer (ADJ), and non-cancer tissues (NC). Moreover, three of these DE piRNAs (piR-48966*, piR-49145, piR-31335*) were differently expressed in both GC and ADJ samples in comparison to NC samples, indicating that the tumor-adjacent tissue was molecularly altered and should not be considered as a normal control. These three piRNAs are potential risk biomarkers for GC, especially piR-48966* and piR-31335*. Furthermore, an in-silico search for mRNAs targeted by the differentially expressed piRNAs revealed that these piRNAs may regulate genes that participate in cancer-related pathways, suggesting that these small non-coding RNAs may be directly and indirectly involved in gastric carcinogenesis.

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhuoyuan Xin ◽  
Luping Zhang ◽  
Mingqing Liu ◽  
Yachen Wang ◽  
Yingli Zhang ◽  
...  

BackgroundHelicobacter pylori (H. pylori) is a type I biological carcinogen, which may cause about 75% of the total incidence of gastric cancer worldwide. H. pylori infection can induce and activate the cancer-promoting signaling pathway and affect the occurrence and outcome of gastric cancer through controlling the regulatory functions of long non-coding RNAs (lncRNAs). However, we have no understanding of the prognostic worth of lncRNAs for gastric cancer patients infected with H. pylori.MethodWe screened differentially expressed lncRNAs using DESeq2 method among TCGA database. And we built the H. pylori infection-related lncRNAs regulatory patterns. Then, we constructed H. pylori infection-based lncRNAs prognostic signatures for gastric cancer patients together with H. pylori infection, via uni-variable and multi-variable COX regression analyses. Based on receiver operator characteristic curve (ROC) analysis, we evaluated the prediction effectiveness for this model.ResultsWe identified 115 H. pylori infection–related genes were differentially expressed among H. pylori–infected gastric cancer tissues versus gastric cancer tissues. Functional enrichment analysis implies that H. pylori infection might interfere with the immune-related pathways among gastric cancer tissues. Then, we built H. pylori infection–related dys-regulated lncRNA regulatory networks. We also identified 13 differentially expressed lncRNAs were associated with prognosis for gastric cancer patients together with H. pylori infection. Kaplan-Meier analysis demonstrated that the lncRNA signatures were correlated with the poor prognosis. What is more, the AUC of the lncRNA signatures was 0.712. Also, this prognostic prediction model was superior to the traditional clinical characters.ConclusionWe successfully constructed a H. pylori–related lncRNA risk signature and nomogram associated with H. pylori–infected gastric cancer patients prognosis, and the signature and nomogram can predict the prognosis of these patients.


Author(s):  
Quan Jiang ◽  
Lingli Chen ◽  
Hao Chen ◽  
Zhaoqing Tang ◽  
Fenglin Liu ◽  
...  

The immune microenvironment plays a critical role in tumor biology. As a critical feature of cancers, stemness is acknowledged as a contributor to the development of drug resistance in gastric cancers (GCs). Long non-coding RNAs (lncRNAs) have been revealed to participate in this process. In this study, we aimed to develop a stemness-related lncRNA signature (SRLncSig) with guiding significance for immunotherapy. Three cohorts (TCGA, Zhongshan, and IMvigor210) were enrolled for analysis. A list of stemness-related lncRNAs (SRlncRNAs) was collected by co-expression strategy under the threshold of coefficient value >0.35 and p-value < 0.05. Cox and Lasso regression analysis was further applied to find out the SRlncRNAs with prognosis-predictive value to establish the SRLncSig in the TCGA cohort. IPS and TIDE algorithms were further applied to predict the efficacy of SRLncSig in TCGA and Zhongshan cohorts. IMvigor210 was composed of patients with clinical outcomes of immunotherapy. The results indicated that SRLncSig not only was confirmed as an independent risk factor for GCs but also identified as a robust indicator for immunotherapy. The patient with a lower SRLncSig score was more likely to benefit from immunotherapy, and the results were highly consistent in three cohorts. In conclusion, our study not only could clarify the correlations between stemness and immunotherapy in GC patients but also provided a model to guide the applications of immunotherapy in clinical practice.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Dan Li ◽  
Yunqing Zhang ◽  
Yulong Li ◽  
Xiaofei Wang ◽  
Fenghui Wang ◽  
...  

Purpose. Gastric cancer is one of the most common cancers in the world. miRNAs play an important role in regulating gene expression by binding with 3 ′ -UTR of the target gene. The aim of this study was to investigate the function of miRNA-149 and FOXC1 in gastric cancer. Patients and Methods. qRT-PCR was used to detect the expression of miRNA-149 and FOXC1 in gastric cancer tissues and cells. Human gastric cancer cell lines AGS and MKN28 were cultured and transfected with miR-149 overexpression plasmid and its control or FOXC1 siRNA and its control. The MTT, colony formation, flow cytometry, wound healing, transwell, and western blotting were performed to examine the function of miRNA-149 and FOXC1 in the development of gastric cancer. What is more, dual-luciferase assay and western blotting were used to demonstrated the relationship between miRNA-149 and FOXC1. Results. miRNA-149 was underexpressed in gastric cancer tissues and cells, while overexpression of miRNA-149 promoted cell apoptosis, retarded cell cycle, and inhibited proliferation and migration in AGS and MKN28 cells. In addition, we showed that miRNA-149 targeted FOXC1. What is more, FOXC1 was highly expressed in gastric cancer tissues and cells; the silencing of FOXC1 inhibited the biological function of AGS and MKN28 cells. Conclusion. miRNA-149 inhibits the biological behavior of gastric cancer by targeting FOXC1, providing a promising target in the treatment of human gastric cancer.


2021 ◽  
Author(s):  
Juan Wang ◽  
Zihan Zheng ◽  
Qinghua Cao ◽  
Xiufen Liu ◽  
Zhiqing Wang

Abstract Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Sergio Lario ◽  
María J. Ramírez-Lázaro ◽  
Aintzane González-Lahera ◽  
José L. Lavín ◽  
Maria Vila-Casadesús ◽  
...  

Abstract Helicobacter pylori infects 4.4 billion individuals worldwide and is considered the most important etiologic agent for peptic ulcers and gastric cancer. Individual response to H. pylori infection is complex and depends on complex interactions between host and environmental factors. The pathway towards gastric cancer is a sequence of events known as Correa’s model of gastric carcinogenesis, a stepwise inflammatory process from normal mucosa to chronic-active gastritis, atrophy, metaplasia and gastric adenocarcinoma. This study examines gastric clinical specimens representing different steps of the Correa pathway with the aim of identifying the expression profiles of coding- and non-coding RNAs that may have a role in Correa’s model of gastric carcinogenesis. We screened for differentially expressed genes in gastric biopsies by employing RNAseq, microarrays and qRT-PCR. Here we provide a detailed description of the experiments, methods and results generated. The datasets may help other scientists and clinicians to find new clues to the pathogenesis of H. pylori and the mechanisms of progression of the infection to more severe gastric diseases. Data is available via ArrayExpress.


2018 ◽  
Vol 19 (12) ◽  
pp. 3881 ◽  
Author(s):  
Kobra Foroughi ◽  
Mohammad Amini ◽  
Amir Atashi ◽  
Habibollah Mahmoodzadeh ◽  
Ute Hamann ◽  
...  

Gastric cancer (GC) is the fifth most common cancer and the third most frequent cause of cancer deaths worldwide. The high death rate associated with GC, and lack of appropriate biomarkers for diagnosis, prognosis, and treatment emphasize the need for identification of novel molecules. Given the emerging roles for long non-coding RNAs (lncRNAs) in cancer development, we studied novel lncRNA candidates involved in gastric carcinogenesis. LncRNA candidate discovery was performed using analyses of available datasets and literature. Validation was done using an internal sample set of GC/normal tissues, and external independent datasets. Network analysis and functional annotation of co-expressed protein coding genes were performed using the weighted gene correlation network analysis (WGCNA) and ingenuity pathway analysis. Two novel lncRNAs, PCAT18 and LINC01133, associated with GC development were identified by analysis of the discovery Gene Expression Omnibus (GEO) datasets. The down-regulation of these genes in GC tissues was successfully validated internally and externally. The results showed a tissue-specific down-regulation of PCAT18 and LINC01133 in gastrointestinal tissues. WGCNA and ingenuity pathway analyses revealed that the genes co-expressed with the two lncRNAs were mostly involved in metabolic pathways and networks of gastrointestinal disease and function. Our findings of a tissue-specific down-regulation of PCAT18 and LINC01133 in gastric and other gastrointestinal cancers imply that these lncRNAs may have a tumor suppressive function in the development of these tumor entities. The two lncRNA biomarkers may contribute to a better understanding of the complex mechanisms of gastric carcinogenesis.


2020 ◽  
Author(s):  
Haili Zhang ◽  
Shi Qian ◽  
Wang Jing

Abstract BackgroundPropofol is the most commonly used general anesthesia for patients with gastric cancer undergoing radical surgery. Studies have suggested that propofol exerts beneficial effects on the immune function of patients with cancer. However, the potential mechanism underlying propofol-mediated immune regulation remains to be elucidated. The present study investigated the regulatory effects of propofol on immune function in patients with gastric cancer undergoing radical surgery. MethodsELISA, reverse transcription-quantitative polymerase chain reaction, western blotting, gene transfection and immunohistochemistry were used to analyze the effects of propofol on gastric cancer cells.ResultsResults demonstrated that propofol general anesthesia resulted in an increased percentage of cluster of differentiation (CD)4+ and CD8+ cells, increased serum concentrations of interleukin (IL)-2 and tumor necrosis factor (TNF)-α, decreased serum concentrations of IL-1β and IL-8 following propofol general anesthesia in gastric cancer patients undergoing radical surgery compared with midazolam. In addition, propofol general anesthesia induced an imbalance in T helper (Th)1/Th2 cells, increased the number of natural killer cells and B cells, decreased the expression of prognostic factors, and improved tumor metastasis, recurrence and survival in patients with gastric cancer compared with midazolam. Furthermore, immunohistochemistry demonstrated that propofol downregulated nuclear factor (NF)-κBp65, and upregulated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) expression level in gastric cancer tissues, downregulated the protein expression levels of NF-κBp65, JAK1, STAT3, TNF-α, IL-1β and IL-8 protein expression in gastric cancer cells isolated from gastric cancer tissues. NF-κBp65 overexpression inhibited propofol-mediated upregulation of JAK1, STAT3, TNF-α, IL-1β and IL-8 expression in gastric cancer cells. ConclusionsThese data indicate that that propofol may increase the number of T cells, stimulate T-cell proliferation, upregulate IL-2 and TNF-α expression, and enhance immune function via the NF-κB-mediated JAK1-STAT3 signaling pathway in patients with gastric cancer undergoing radical surgery.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1021-A1021
Author(s):  
Junichi Okada ◽  
Eijiro Yamada ◽  
Tsugumichi Saito ◽  
Yasuyo Nakajima ◽  
Atsushi Ozawa ◽  
...  

Abstract Nucleobindin-2 (NUCB2) is a 396-amino acid protein, cleaved into the N-terminal nesfatin-11-82, nesfatin-285-163 and the C-terminal nesfatin-3166-396. NUCB2 contains a signal peptide, a leucine zipper structure, two Ca2+ binding EF-hand domains, and has a wide variety of basic cellular functions. NUCB2 is also a precursor protein of nesfatin-1, which was originally identified in hypothalamic nuclei, and which is a regulatory factor involved in the central control of food intake and energy balance. There are several reports indicating that NUCB2 is also expressed in various human peripheral tissues. Moreover, recent studies have reported that high levels of NUCB2 mRNA and protein are a potent prognostic factor for prostate cancer, endometrial carcinoma, and breast cancer. NUCB2 was also identified as a potential tumor antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals. However, theclinicopathological significance of NUCB2 expression in gastric cancer has still not been elucidated. Therefore, we examined NUCB2 expression in a large number of gastric cancer patients, using immunohistochemistry, to explore its clinicopathological significance. To explore this, we aimed to investigate the NUCB2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemistry analysis. In our study, NUCB2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of NUCB2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and clinical stage. Furthermore, the expression level of NUCB2 protein was independent predictor of progression-free survival. In summary, NUCB2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.


2019 ◽  
Vol 14 ◽  
Author(s):  
Lishui Shen ◽  
Guilin Shen ◽  
Xiaoli Lu ◽  
Guomin Ding ◽  
Xiaofeng Hu

Atrial fibrillation (AF) is one of the most common heart arrhythmic disorders all over the world. However, it is worth noting that the mechanism underlying AF is still dimness. In this study, we implemented a series of bioinformatics methods to explore the mechanisms of lncRNAs underlying AF pathogenesis. The present study analyzed the public datasets (GSE2240 and GSE115574) to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in the progression of AF. Totally, 71 differentially expressed lncRNAs and 390 DEGs were identified in AF.Next, we performed bioinformatics analyses to explore the functions of lncRNAs in AF. Gene Ontology (GO) analysis indicated that differentially expressed lncRNAs were involved in regulating multiple key biological processes, such as cell cycle and signal transduction. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated these lncRNAs were associated with the regulation of MAPK and Wnt signaling pathways. Eight lncRNAs (RP5-1154L15.2, RP11-339B21.15, RP11-448A19.1, RP11-676J12.4, LOC101930415, MALAT1, NEAT1, and PWAR6) were identified to be key lncRNAs and widely co-expressed with a series of differentially expressed genes (DEGs). Although further validation was still needed, our study may be helpful to elucidate the mechanisms of lncRNAs underlying AF pathogenesis and providing further insight into identifying novel biomarkers for AF.


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