N6-methyladenosine Reader YTHDF1-induced lncRNA DLGAP1-AS2 Promotes the c-Myc Mediated Gastric Cancer Aerobic Glycolysis

Abstract Background: Emerging data has demonstrated the essential function of N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) in human tumorigenesis. Nevertheless, the regulation of m6A-lncRNA approach on gastric cancer (GC) tumorigenesis is unclear. Methods: LncRNA expression profile data was derived from GEO. M6A profile was screened using Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The metabolism assays were conducted using quantitative analysis of glucose, lactate, ATP and extracellular acidification rate (ECAR). The m6A level of specific RNA was identified using MeRIP-qPCR. The molecular interaction was detected using RIP assay.Results: In the findings, results showed that enhanced DLGAP1-AS2 expression was correlated with advanced pathological stage and poor prognosis. Functionally, DLGAP1-AS2 promoted the aerobic glycolysis and knockdown of DLGAP1-AS2 suppressed the tumor growth of GC cells. Mechanistically, m6A reader YTHDF1 accelerated the enrichment of DLGAP1-AS2 in GC. Moreover, DLGAP1-AS2 interacted with YTHDF1 to integrate c-Myc mRNA, thereby enhancing the stability of c-Myc mRNA through DLGAP1-AS2/m6A/YTHDF1/c-Myc mRNA. Conclusions: In conclusion, our work indicates a novel m6A-maintained lncRNA DLGAP1-AS2 in the GC aerobic glycolysis, disclosing a m6A-reader-dependent modality regulation.

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METTL3-Mediated DLGAP1 Antisense RNA 2 Promotes Gastric Cancer Tumorigenesis Through Facilitating C-Myc-Dependent Warburg Effect

10.21203/rs.3.rs-1135467/v1 ◽

2021 ◽

Author(s):

Changshun Yang ◽

Yu Zhang ◽

Xuefei Cheng ◽

Weihua Li

Keyword(s):

Gastric Cancer ◽

Antisense Rna ◽

Warburg Effect ◽

Aerobic Glycolysis ◽

Dependent Manner ◽

Rna Immunoprecipitation ◽

The Stability ◽

A Site ◽

Rip Assay ◽

Site Binding

Abstract Background The critical roles of N6-methyladenosine (m6A) modification have been demonstrated by more and more evidence. However, the cross-talking of m6A and long non-coding RNAs (lncRNAs) in gastric cancer (GC) tumorigenesis is still unclear. Here, our work focused on the functions and molecular mechanism of m6A-modified lncRNA DLGAP1 antisense RNA 2 (DLGAP1-AS2) in GC. Methods LncRNA expression profile data was derived from GEO. M6A profile was screened using Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The metabolism assays were conducted using quantitative analysis of glucose, lactate, ATP and extracellular acidification rate (ECAR). The m6A level of specific RNA was identified using MeRIP-qPCR. The molecular interaction was detected using RIP assay. Results Microarray analysis found that lncRNA DLGAP1-AS2 up-regulated in GC cells. Clinical data showed that DLGAP1-AS2 high-expression was correlated with advanced pathological stage and poor prognosis. Functionally, DLGAP1-AS2 promoted the Warburg effect (aerobic glycolysis) and knockdown of DLGAP1-AS2 suppressed the tumor growth of GC cells. Mechanistically, m6A methyltransferase METTL3 enhanced the stability of DLGAP1-AS2 via m6A site binding. Moreover, DLGAP1-AS2 interacted with YTHDF1 to enhance the stability of c-Myc mRNA through DLGAP1-AS2/m6A/YTHDF1/c-Myc mRNA. Conclusions In conclusion, our work indicates the functions of m6A-modified DLGAP1-AS2 in the GC aerobic glycolysis, disclosing a potential m6A-dependent manner for GC treatment.

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The correlation between lncRNAs and Helicobacter pylori in gastric cancer

Pathogens and Disease ◽

10.1093/femspd/ftaa004 ◽

2019 ◽

Vol 77 (9) ◽

Author(s):

Narges Dastmalchi ◽

Seyed Mahdi Banan Khojasteh ◽

Mirsaed Miri Nargesi ◽

Reza Safaralizadeh

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Molecular Mechanisms ◽

Gastrointestinal Diseases ◽

Mechanisms Of Action ◽

Molecular Pathways ◽

Gastric Diseases ◽

Non Coding Rnas ◽

H Pylori ◽

The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

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Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications

Molecular Cancer ◽

10.1186/s12943-021-01396-6 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xiao-Huan Tang ◽

Ting Guo ◽

Xiang-Yu Gao ◽

Xiao-Long Wu ◽

Xiao-Fang Xing ◽

...

Keyword(s):

Gastric Cancer ◽

Noncoding Rnas ◽

Tumour Microenvironment ◽

Clinical Applications ◽

Biological Molecules ◽

Biological Functions ◽

Membrane Structures ◽

Chemical Substances ◽

Expression Levels ◽

The Stability

AbstractExosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. Exosomes are derived from nearly all types of cells and exist in all body fluids. Noncoding RNAs (ncRNAs) are among the most abundant contents in exosomes, and some ncRNAs with biological functions are specifically packaged into exosomes. Recent studies have revealed that exosome-derived ncRNAs play crucial roles in the tumorigenesis, progression and drug resistance of gastric cancer (GC). In addition, regulating the expression levels of exosomal ncRNAs can promote or suppress GC progression. Moreover, the membrane structures of exosomes protect ncRNAs from degradation by enzymes and other chemical substances, significantly increasing the stability of exosomal ncRNAs. Specific hallmarks within exosomes that can be used for exosome identification, and specific contents can be used to determine their origin. Therefore, exosomal ncRNAs are suitable for use as diagnostic and prognostic biomarkers or therapeutic targets. Regulating the biogenesis of exosomes and the expression levels of exosomal ncRNAs may represent a new way to block or eradicate GC. In this review, we summarized the origins and characteristics of exosomes and analysed the association between exosomal ncRNAs and GC development.

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AC016745.3 Regulates the Transcription of AR Target Genes by Antagonizing NONO

Life ◽

10.3390/life11111208 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1208

Author(s):

Yali Lu ◽

Xuechao Wan ◽

Wenhua Huang ◽

Lu Zhang ◽

Jun Luo ◽

...

Keyword(s):

Transcriptional Activity ◽

Target Genes ◽

Cellular Proliferation ◽

Mechanisms Of Action ◽

Adenocarcinoma Cell Line ◽

Specific Mechanism ◽

Rna Immunoprecipitation ◽

Non Coding Rnas ◽

And Migration ◽

Proliferation And Migration

The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examines the function and mechanisms of action of lncRNA AC016745.3 in the development of PCa. It shows that dihydrotestosterone (DHT) results in the AR-dependent suppression of AC016745.3 expression in the LNCaP androgen-sensitive human prostate adenocarcinoma cell line. In addition, overexpression of AC016745.3 inhibits the proliferation and migration of PCa cells, and suppresses the expression of AR target genes. This research also demonstrates that the protein NONO interacts with AR and functions as an AR co-activator, promoting AR transcriptional activity. Furthermore, using RNA immunoprecipitation (RIP)-PCR experiments, the study demonstrates that both NONO and AR can bind AC016745.3. Moreover, cell phenotypic experiments reveal that NONO can promote cellular proliferation and migration, and that AC016745.3 can partially antagonize the pro-oncogenic functions of NONO in PCa cells. In summary, the results indicate that AC016745.3 can bind NONO, suppressing its ability to promote AR-dependent transcriptional activity. Furthermore, DHT-dependent suppression of AC016745.3 expression can enhance NONO’s promotion effect on AR.

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Integrated Analysis of Stemness-Related LncRNAs Helps Predict the Immunotherapy Responsiveness of Gastric Cancer Patients

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.739509 ◽

2021 ◽

Vol 9 ◽

Author(s):

Quan Jiang ◽

Lingli Chen ◽

Hao Chen ◽

Zhaoqing Tang ◽

Fenglin Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Independent Risk Factor ◽

Critical Role ◽

Tumor Biology ◽

Integrated Analysis ◽

Lasso Regression ◽

Immune Microenvironment ◽

Critical Feature ◽

Non Coding Rnas ◽

Gastric Cancer Patients

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.

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Promising Advances in LINC01116 Related to Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.736927 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yating Xu ◽

Xiao Yu ◽

Menggang Zhang ◽

Qingyuan Zheng ◽

Zongzong Sun ◽

...

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Lung Cancer ◽

Cancer Colorectal ◽

Malignant Tumors ◽

Biological Processes ◽

Aberrant Expression ◽

Protein Coding ◽

Future Studies ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs) are RNAs with a length of no less than 200 nucleotides that are not translated into proteins. Accumulating evidence indicates that lncRNAs are pivotal regulators of biological processes in several diseases, particularly in several malignant tumors. Long intergenic non-protein coding RNA 1116 (LINC01116) is a lncRNA, whose aberrant expression is correlated with a variety of cancers, including lung cancer, gastric cancer, colorectal cancer, glioma, and osteosarcoma. LINC01116 plays a crucial role in facilitating cell proliferation, invasion, migration, and apoptosis. In addition, numerous studies have recently suggested that LINC01116 has emerged as a novel biomarker for prognosis and therapy in malignant tumors. Consequently, we summarize the clinical significance of LINC01116 associated with biological processes in various tumors and provide a hopeful orientation to guide clinical treatment of various cancers in future studies.

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PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression

Frontiers in Oncology ◽

10.3389/fonc.2021.767116 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qingmin Sun ◽

Mengyun Yuan ◽

Hongxing Wang ◽

Xingxing Zhang ◽

Ruijuan Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Cancer Metastasis ◽

Nuclear Translocation ◽

Aerobic Glycolysis ◽

Metabolic Reprogramming ◽

Migration And Invasion ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Mesenchymal Transition

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients.Chemical Compounds Studied in this ArticleRutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

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Development of Iceberg Profiling Technology

10.1115/omae2021-62950 ◽

2021 ◽

Author(s):

Jonathon Bruce ◽

Renat Yulmetov ◽

Tony King ◽

Freeman Ralph ◽

Adel Younan

Keyword(s):

Large Scale ◽

Analysis Tool ◽

Profile Data ◽

Grand Banks ◽

Drift Model ◽

Iceberg Drift ◽

Large Scale Field ◽

Loads Analysis ◽

Rapid Generation ◽

The Stability

Abstract Iceberg management on the Grand Banks of Newfoundland, Canada is currently carried out without knowledge of the underwater shape of the iceberg. An iceberg profiling system is being developed to integrate the rapid generation of 3D iceberg shape data with a collection of tools that utilize the data to provide recommendations, intended to improve iceberg management effectiveness. The intent is for the system to be operated by vessel crew with minimal training. The system utilizes a LiDAR and a pole mounted multibeam sonar to profile the iceberg sail and keel, respectively. A vessel equipped with the profiling system circles an iceberg twice to collect a profile, a process that on average requires approximately 15–30 minutes. The data is collected in the form of a point cloud, which must be de-noised and corrected for both drift and rotation of the iceberg. Tools have been developed to assess the stability of the iceberg, and to consider the shape of the iceberg relative to towing net dimensions, to provide guidance to the operator regarding the recommended towing direction to avoid iceberg rolling or net slippage events. Other applications of the profile data include an impact loads analysis tool that determines the distribution of potential iceberg loads in the event of a collision with a given platform, and an operational iceberg drift model that uses the iceberg shape to improve iceberg drift forecasts. Large-scale field programs were carried out in both 2018 and 2019 as part of the development process for the system. Data collected has shown that iceberg characteristics have changed significantly when compared to iceberg profile data collected in the 1980s. For a given iceberg waterline length, the more recent data shows significantly reduced drafts. The 1980s iceberg dataset currently dominates the data used as the basis for assessing iceberg loads on surface facilities and iceberg risk to subsea assets. Reduced iceberg drafts will result in reduced risk to subsea facilities and pipelines. These results and observations demonstrate the usefulness of the iceberg profiling system as an environmental monitoring tool, and the data collected has design and operational applications. The development and capabilities of the system are presented, as well as the comparison of the 1980’s and newer iceberg datasets and implications for iceberg risk to facilities on the Grand Banks and surrounding regions.

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Cross-sectional study of human coding- and non-coding RNAs in progressive stages of Helicobacter pylori infection

Scientific Data ◽

10.1038/s41597-020-00636-6 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Sergio Lario ◽

María J. Ramírez-Lázaro ◽

Aintzane González-Lahera ◽

José L. Lavín ◽

Maria Vila-Casadesús ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Expression Profiles ◽

Gastric Carcinogenesis ◽

Individual Response ◽

Peptic Ulcers ◽

Gastric Diseases ◽

Sequence Of Events ◽

Non Coding Rnas ◽

H Pylori

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.

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