scholarly journals Genome-Wide Characterization of RNA Editing Sites in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Javad Behroozi ◽  
Shirin Shahbazi ◽  
Mohammad Reza Bakhtiarizadeh ◽  
Habibollah Mahmoodzadeh
Keyword(s):  
Gastric Cancer ◽  
Rna Editing ◽  
Gastric Adenocarcinoma ◽  
Cancer Progression ◽  
Variant Calling ◽  
Distinct Pattern ◽  
Rna Seq ◽  
Comprehensive Overview ◽  
Protein Coding ◽  
Cancer Tissues

RNA editing is a posttranscriptional nucleotide modification in humans. Of the various types of RNA editing, the adenosine to inosine substitution is the most widespread in higher eukaryotes, which is mediated by the ADAR family enzymes. Inosine is recognized by the biological machinery as guanosine; therefore, editing could have substantial functional effects throughout the genome. RNA editing could contribute to cancer either by exclusive editing of tumor suppressor/promoting genes or by introducing transcriptomic diversity to promote cancer progression. Here, we provided a comprehensive overview of the RNA editing sites in gastric adenocarcinoma and highlighted some of their possible contributions to gastric cancer. RNA-seq data corresponding to 8 gastric adenocarcinoma and their paired nontumor counterparts were retrieved from the GEO database. After preprocessing and variant calling steps, a stringent filtering pipeline was employed to distinguish potential RNA editing sites from SNPs. The identified potential editing sites were annotated and compared with those in the DARNED database. Totally, 12362 high-confidence adenosine to inosine RNA editing sites were detected across all samples. Of these, 12105 and 257 were known and novel editing events, respectively. These editing sites were unevenly distributed across genomic regions, and nearly half of them were located in 3 ′ UTR. Our results revealed that 4868 editing sites were common in both normal and cancer tissues. From the remaining sites, 3985 and 3509 were exclusive to normal and cancer tissues, respectively. Further analysis revealed a significant number of differentially edited events among these sites, which were located in protein coding genes and microRNAs. Given the distinct pattern of RNA editing in gastric adenocarcinoma and adjacent normal tissue, edited sites have the potential to serve as the diagnostic biomarkers and therapeutic targets in gastric cancer.

scholarly journals Comprehensive Characterization of RNA Editing in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis

2020 ◽  
Author(s):  
Javad Behroozi ◽  
Shirin Shahbazi ◽  
Mohammad Reza Bakhtiarizadeh ◽  
Habibollah Mahmoodzadeh
Keyword(s):  
Gastric Cancer ◽  
Rna Editing ◽  
Gastric Adenocarcinoma ◽  
Cancer Progression ◽  
Variant Calling ◽  
Distinct Pattern ◽  
Rna Seq ◽  
Comprehensive Overview ◽  
Protein Coding ◽  
Genomic Regions

Abstract RNA editing is a post-transcriptional nucleotide modification in humans. Of the various types of RNA editing, the adenosine to inosine substitution is the most widespread in higher eukaryotes, which is mediated by ADAR family enzyme. Inosine is recognized by the biological machineries as guanosine, therefore, editing can potentially rendering substantial functional effects throughout the genome, depending on where it located. RNA editing could contribute to cancer by either exclusive editing of tumor suppressor/promoting genes or by introducing transcriptomic diversity to promote cancer progression. Here, we provided a comprehensive overview of the RNA editing sites in gastric adenocarcinoma and highlighted some of their possible contributions to gastric cancer. RNA-seq data corresponding to 8 gastric adenocarcinoma and their paired non-tumor counterparts were retrieved from GEO database. After pre-possessing and variant calling steps, a stringent filtering pipeline was employed to distinguish potential RNA editing sites from SNPs. The identified potential editing sites were annotated and compared with those in DARNED database. Totally, 12362 high-confidence adenosine to inosine RNA editing sites were detected across all samples. Of these, 12105 and 257 were known and novel editing events, respectively. These editing sites were unevenly distributed across genomic regions, nearly half of them were located in 3´UTR. Indeed, 4868, 3985 and 3509 editing sites were found to be common in both tissue, normal specific and cancer specific, respectively. Further analysis revealed significant number of differentially edited events among these sites, which were located in protein coding genes and microRNAs. Given the distinct pattern of RNA editing in gastric adenocarcinoma and adjacent normal tissue, edited sites have the potential to serve as biomarkers and therapeutic targets in gastric cancer diagnose, management and treatment.

scholarly journals Automated Isoform Diversity Detector (AIDD): A pipeline for investigating transcriptome diversity of RNA-seq data

2020 ◽  
Author(s):  
Noel-Marie Plonski ◽  
Emily Johnson ◽  
Madeline Frederick ◽  
Heather Mercer ◽  
Gail Fraizer ◽  
...  
Keyword(s):  
Rna Editing ◽  
Large Scale ◽  
Neural Progenitor Cells ◽  
Viral Infections ◽  
Variant Calling ◽  
Rna Seq ◽  
Major Mechanism ◽  
Isoform Diversity ◽  
Adar Editing ◽  
Transcriptome Diversity

AbstractBackgroundAs the number of RNA-seq datasets that become available to explore transcriptome diversity increases, so does the need for easy-to-use comprehensive computational workflows. Many available tools facilitate analyses of one of the two major mechanisms of transcriptome diversity, namely, differential expression of isoforms due to alternative splicing, while the second major mechanism - RNA editing due to post-transcriptional changes of individual nucleotides – remains under-appreciated. Both these mechanisms play an essential role in physiological and diseases processes, including cancer and neurological disorders. However, elucidation of RNA editing events at transcriptome-wide level requires increasingly complex computational tools, in turn resulting in a steep entrance barrier for labs who are interested in high-throughput variant calling applications on a large scale but lack the manpower and/or computational expertise.ResultsHere we present an easy-to-use, fully automated, computational pipeline (Automated Isoform Diversity Detector, AIDD) that contains open source tools for various tasks needed to map transcriptome diversity, including RNA editing events. To facilitate reproducibility and avoid system dependencies, the pipeline is contained within a pre-configured VirtualBox environment. The analytical tasks and format conversions are accomplished via a set of automated scripts that enable the user to go from a set of raw data, such as fastq files, to publication-ready results and figures in one step. A publicly available dataset of Zika virus-infected neural progenitor cells is used to illustrate AIDD’s capabilities.ConclusionsAIDD pipeline offers a user-friendly interface for comprehensive and reproducible RNA-seq analyses. Among unique features of AIDD are its ability to infer RNA editing patterns, including ADAR editing, and inclusion of Guttman scale patterns for time series analysis of such editing landscapes. AIDD-based results show importance of diversity of ADAR isoforms, key RNA editing enzymes linked with the innate immune system and viral infections. These findings offer insights into the potential role of ADAR editing dysregulation in the disease mechanisms, including those of congenital Zika syndrome. Because of its automated all-inclusive features, AIDD pipeline enables even a novice user to easily explore common mechanisms of transcriptome diversity, including RNA editing landscapes.

scholarly journals Mutational analysis of driver genes with tumor suppressive and oncogenic roles in gastric cancer

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3585 ◽  
Author(s):  
Tianfang Wang ◽  
Yining Liu ◽  
Min Zhao
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Complex Disease ◽  
Mutational Analysis ◽  
Driver Mutations ◽  
Driver Genes ◽  
Protein Coding ◽  
Mirna Genes ◽  
Genetic Mechanisms ◽  
New Treatment

Gastric cancer (GC) is a complex disease with heterogeneous genetic mechanisms. Genomic mutational profiling of gastric cancer not only expands our knowledge about cancer progression at a fundamental genetic level, but also could provide guidance on new treatment decisions, currently based on tumor histology. The fact that precise medicine-based treatment is successful in a subset of tumors indicates the need for better identification of clinically related molecular tumor phenotypes, especially with regard to those driver mutations on tumor suppressor genes (TSGs) and oncogenes (ONGs). We surveyed 313 TSGs and 160 ONGs associated with 48 protein coding and 19 miRNA genes with both TSG and ONG roles. Using public cancer mutational profiles, we confirmed the dual roles of CDKN1A and CDKN1B. In addition to the widely recognized alterations, we identified another 82 frequently mutated genes in public gastric cancer cohort. In summary, these driver mutation profiles of individual GC will form the basis of personalized treatment of gastric cancer, leading to substantial therapeutic improvements.

scholarly journals miR-1915-3p inhibits Bcl-2 expression in the development of gastric cancer

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Hong-wei Cui ◽  
Wen-yan Han ◽  
Li-na Hou ◽  
Ling Yang ◽  
Xian Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Kidney Diseases ◽  
B Cell Lymphoma ◽  
Gene Expressions ◽  
Gastric Cancer Cells ◽  
Apoptotic Protein ◽  
Gastric Cancer Stem Cells ◽  
Cancer Tissues ◽  
Development Of Gastric Cancer

Abstract Many gene expressions changed during the development of gastric cancer, and non-coding RNAs including microRNAs (miRNAs) have been found to regulate cancer progression by participating in the process of tumor cell growth, migration, invasion and apoptosis. Our previous study has identified 29 miRNAs that are highly expressed in gastric cancer stem cells. One of these miRNAs, miR-1915-3p, has shown great potential as a diagnostic and prognostic biomarker for the cancers in liver, colon and thyroid, as well as in immune and kidney diseases. Herein, we found that miR-1915-3p exhibited low expression level in differentiated gastric cancer cell lines and gastric cancer tissues. It was found that the miR-1915-3p inhibited the growth of gastric cancer cells and thus promoted cell apoptosis. We discovered that the expressions of miR-1915-3p were significantly correlated to the lymph node metastasis and overall survival of patients with gastric cancer. Further study showed that there was a negative correlation between miR-1915-3p and Bcl-2 (B cell lymphoma/leukemia-2) expression, suggesting that Bcl-2 was a target gene of miR-1915-3p. Hence, miR-1915-3p possibly contributes to the development and progression of gastric cancer by inhibiting the anti-apoptotic protein Bcl-2. The finding provides a potential therapeutic strategy for gastric cancer.

scholarly journals LINC00641/miR-582-5p mediate oxaliplatin resistance by activating autophagy in gastric adenocarcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yunfeng Hu ◽  
Yani Su ◽  
Xia Lei ◽  
Hong Zhao ◽  
Lelin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Resistant Cell ◽  
Specific Mechanism ◽  
Gastric Cancer Cells ◽  
Down Regulation ◽  
Cancer Tissues ◽  
Cell Migration And Proliferation

Abstract The poor prognosis of gastric adenocarcinoma is partly due to chemotherapy failure, especially the oxaliplatin-based chemotherapy. However, the specific mechanism of oxaliplatin resistance is unclear. We aim to find the roles that LINC00641 and miR-582-5p play in regulating oxaliplatin resistance. Quantitative reverse transcriptase-PCR was used to evaluate the expression of LINC00641 and microRNA-582-5p (miR-582-5p) in gastric cancer both in vivo and in vitro. Transwell and CCK-8 assays were performed; and LC3 I/II and p62 were detected by western blot to evaluate the activation of autophagy. LINC00641 expression was associated with prognosis and oxaliplatin resistance in patients with gastric adenocarcinoma. The expression of LINC00641 was higher in gastric cancer tissues; whereas miR-582-5p was down-regulated in gastric cancer tissues. Moreover, LINC00641 was highly expressed in oxaliplatin-resistant cell lines and miR-582-5p was down-regulated. In addition, LINC00641 negatively regulated the expression of miR-582-5p. With regard to biological functions, down-regulation of LINC00641 suppressed cell migration and proliferation. Further experiments indicated that down-regulation of LINC00641 inhibited the autophagy process, making gastric cancer cells more sensitive to oxaliplatin. LINC00641 and miR-582-5p are biomarkers for predicting overall survival, as they were involved in regulating oxaliplatin resistance by altering autophagy in gastric adenocarcinoma.

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 MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yixun Lu ◽  
Benlong Zhang ◽  
Baohua Wang ◽  
Di Wu ◽  
Chuang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cancer Tissues ◽  
Gastric Cancer Progression

Abstract Background Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. Methods Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. Results GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. Conclusions MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

scholarly journals LncRNA ELFN1-AS1 Upregulates TRIM29 to Promote Gastric Cancer Progression by Suppressing miR-211-3p

2021 ◽  
Author(s):  
Jinxi Huang ◽  
Weiwei Yuan ◽  
Beibei Chen ◽  
Gaofeng Li ◽  
Xiaobing Chen
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Vitality ◽  
Reverse Transcription Quantitative Pcr ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Cancer Tissues

Abstract BackgroundExtracellular leucine rich repeat and fibronectin type III domain containing 1-antisense RNA 1 (ELFN1-AS1) was upregulated in tumors. Nevertheless, the biological functions of ELFN1-AS1 in gastric cancer are not fully understood.MethodsThe ELFN1-AS1, miR-211-3p and TRIM29 expression levels were determined by reverse transcription-quantitative PCR. CCK8, EDU and colony formation assays were done to test the GC cell vitality. The migratory and invasive capabilities of GC cells were further measured by transwell invasion and cell scratch assays. The ceRNA activity of ELFN1-AS1 for TRIM29 via miR-211-3pp was ascertained through pull down, RIP and luciferase reporter assays.ResultsELFN1-AS1 and TRIM29 were robustly expressed in gastric cancer tissues and negatively associated overall survival time of patients. The ELFN1-AS1 silence blocked the proliferation, migration and invasion of GC cells. The oncogenic role of ELFN1-AS1 was recognized to be modulated by miR-211-3pp, which competitively bind to 3'UTR TRIM29 and resulted in the reduced expression of TRIM29.ConclusionELFN1-AS1 maintained the tumorigensis of GC cells by ELFN1-AS1/miR-211-3pp/TRIM29 axis, suggesting that intervention targeting this axis may be warranted for GC treatment.

scholarly journals Identification of associated molecular events in Helicobacter pylori infection and gastric cancer through integrated computational analysis of Microarray and RNA-Seq datasets

2021 ◽  
Author(s):  
Sabaoon Zeb ◽  
Rehan Zafar Paracha ◽  
Maryum Nisar ◽  
Rimsha Khalid ◽  
Zartasha Mustansar ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Progression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
World Health ◽  
Separate Analysis ◽  
Rna Seq ◽  
Molecular Events

Abstract According to the World Health Organization, Gastric cancer (GC) is the third leading cause of death worldwide, where, the major precursor of cancer progression is infection with Helicobacter pylori. It has been reported that 50% of the total populace is infected with H.pylori, while in 80% the ulcer emerges in later stages of the infection. Although extensive separate analysis has been performed on H.pylori infection and GC data, however, there is a need to perform comparative analysis to identify the cross-talk between the conditions and to hunt significant molecular events that occurs during H.pylori induced GC. The aim of this multi-population study was to identify common molecular events and potential bio-markers against H.pylori induced GC. We performed microarray and RNA-seq analysis on publicly available H.pylori infection, gastritis, H.pylori induced GC and GC datasets to obtain Differentially Expressed Genes (DEGs). After obtaining the DEGs, integrative analysis, functional enrichment analysis and network biology approaches were utilized to identify common markers and hub genes between various disease conditions. Functional enrichment analysis revealed the DEGs of H.pylori infection, gastritis, H.pylori induced GC and GC were strongly associated with spliceosome, adherens junction, focal adhesion and ribosome. Being one of the common DEG, and highly interactive hub protein in the networks of all the conditions, translationally controlled tumour protein (TPT1) was identified as a significant predictive biomarker for early prognosis and diagnosis of H.pylori induced GC. Therefore, the mechanisms behind TPT1 should be further studied using in vitro cell-based functional assays, to determine its role in the progression of H.pylori induced GC.

Phase II trial of palbociclib in patients with advanced esophageal or gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 68-68 ◽  
Author(s):  
Thomas Benjamin Karasic ◽  
Mark H. O'Hara ◽  
Ursina R. Teitelbaum ◽  
Nevena Damjanov ◽  
Bruce J. Giantonio ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gastric Adenocarcinoma ◽  
Cancer Progression ◽  
Phase Ii ◽  
Squamous Cell ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Carcinoma Of The Esophagus

68 Background: Dysregulation of the cell cycle is a hallmark of cancer. Progression through the G1/S transition requires phosphorylation of retinoblastoma (RB) by cyclin-dependent kinases 4 and 6 (CDK4/6), which are regulated by cyclins D and E. A positive feedback loop between apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase pathway, and cyclin D1 has been shown to drive cell proliferation in gastric cancer. In addition, amplification of cyclin D loci and/or activating mutations in CDKs are frequent molecular aberrations in gastroesophageal malignancies. We hypothesized that palbociclib, a potent inhibitor of CDK4/6 would disrupt proliferative signaling, and arrest the growth of gastric cancer. We conducted a phase II trial of palbociclib in gastric and esophageal cancers as an initial test of efficacy. Methods: We screened 38 subjects with gastric, GE junction, or esophageal cancer for RB nuclear expression by immunohistochemistry, and 38/38 (100%) were positive. We enrolled 21 subjects, of whom 5 had gastric adenocarcinoma, 3 had GE junction adenocarcinoma, 8 had esophageal adenocarcinoma, and 5 had esophageal squamous cell carcinoma. Four of 19 subjects tested positive for CCND1 overexpression by FISH. Patients received 125mg daily of palbociclib for days 1-21 of 28-day cycles. Results: Subjects remained on treatment for a median of 1.7 months. By the initial 2-month assessment, 5 of 21 subjects had stable disease, and 16 subjects had progressive disease by imaging and/or clinical progression. No objective responses were seen. The maximum duration of therapy was 5.5 months in two subjects. One of these subjects had progressing HER2-amplified gastric adenocarcinoma, and continued concurrent trastuzumab with palbociclib, while the other had squamous cell carcinoma of the esophagus. Grade 3 or 4 cytopenias occurred in 9 of 21 subjects (43%), with neutropenia in 8 (38%), anemia in 4 (19%), and thrombocytopenia in 1 (5%). One subject discontinued therapy due to grade 4 thrombocytopenia with GI bleed. All other subjects discontinued therapy due to disease progression. Conclusions: Palbociclib has modest single-agent activity in gastroesophageal tumors despite universal RB expression. Clinical trial information: NCT01037790.

Sign in / Sign up

Export Citation Format

Share Document