microRNAs In Gastric Cancer Research Articles

Bibliometric and visualized analysis of global research on microRNAs in gastric cancer: from 2013 to 2023.

Gastric cancer (GC) imposes a heavy burden on global public health, and microRNAs (miRNAs) play a crucial role in the diagnosis and treatment of GC. Therefore, it is necessary to clarify the hotspots and frontiers in the field of miRNAs in GC to guide future research. A total of 2,051 publications related to miRNAs in GC from January 2013 to December 2023 were searched from the Web of Science Core Collection database. CiteSpace was used to identify research hotspots and delineate developmental trends. In the past decade, China, Nanjing Medical University, and Ba Yi were the most contributing research country, institute, and author in this field, respectively. The role of miRNAs as biomarkers in GC, the mechanism of miRNAs in the progression of GC, and the impact of the mutual effects between miRNAs and Helicobacter pylori on GC have been regarded as the research hotspots. The mechanisms of miRNAs on glucose metabolism and the application of the roles of circular RNAs as miRNA sponges in GC treatment will likely be frontiers. Overall, this study called for strengthened cooperation to identify targets and therapeutic regimes for local specificity and high-risk GC types, and to promote the translation of research results into clinical practice.

Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets.

Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease.

Novel Biomarkers of microRNAs in Gastric Cancer: An Overview from Diagnosis to Treatment

Abstract: Gastric cancer (GC) is the fourth most frequent disease in the world and the second cause of cancer-related death. In this way, over 80% of diagnoses are made in the middle to advanced de-grees of the disease, underscoring the requirement for innovative biomarkers that can be identified quickly. Meaningly, biomarkers that can complement endoscopic diagnosis and be used to detect patients with a high risk of GC are desperately needed. These biomarkers will allow for the accurate prediction of therapy response and prognosis in GC patients, as well as the development of an opti-mal treatment strategy for each individual. Conspicuously, microRNAs (miRNAs) and small non-coding RNA regulate the expression of target mRNA, thereby modifying critical biological mecha-nisms. According to the data, abnormally miRNAs expression in GC is linked to tumor growth, car-cinogenesis, aggression, and distant metastasis. Importantly, miRNA expression patterns and next-generation sequencing (NGS) can also be applied to analyze different kinds of tissues and cancers. Given the high death rates and poor prognosis of GC, and the absence of a clinical diagnostic factor that is adequately sensitive to GC, research on novel sensitive and specific markers for GC diagno-sis is critical. In this review, we examine the latest research findings that suggest the feasibility and clinical utility of miRNAs in GC.

Significance of liquid biopsy using urinary microRNA in gastric cancer

Significance of liquid biopsy using urinary microRNA in gastric cancer

Identification of Key Circulating Exosomal microRNAs in Gastric Cancer.

Exosomal miRNAs (EmiRs) can be used for prediction of gastric cancer (GC) development. Supposedly, both plasma and urinary microRNAs can also be potential biomarkers for screening, but the diagnostic values of EmiRs in blood and urine are not fully studied. We here collected both types of samples from GC patients and healthy individuals and conducted miRNA sequencing to identify key members of EmiRs in GC. The exosomes samples derived from blood and urine were collected from 3 healthy individuals and 7 GC patients. Differentially expressed miRNAs (DEmiRNAs) were acquired, ontology enrichment analysis and Protein-protein Interaction (PPI) enrichment analysis were performed. There were 8 DEmiRNAs in the serum and 3 DEmiRNAs in the urine. For GC patients, there were three up-regulated DEmiRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) in the serum exosomes, and one up-regulated DEmiRNA (hsa-miR-1246) in the urinary exosomes. Using miRNA target prediction databases, we found 418 common targets of hsa-miR-15b-3p, 35 common targets of hsa-miR-151a-3p, 117 common targets of hsa-miR-130b-3p, and 357 common targets of hsa-miR-1246. Some commonly enriched ontology terms were found, including GO BP terms like cell surface receptor signaling pathway involved in cell-cell signaling, positive regulation of catabolic process, morphogenesis of an epithelium, and GO CC terms perinuclear region of cytoplasm. The PPI network show some key nodes, including TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1. Together, this study provided an integrative analysis of expression profile of key circulating exosomal microRNAs. Four key exosomal miRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) and the interaction network or enrichments based on their targets (TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1) may provide a reference of the molecular mechanisms in the GC development.

Vitamin D modulation and microRNAs in gastric cancer: prognostic and therapeutic role.

Gastric adenocarcinoma arises after a complex interaction between the host and environmental factors. Tumor location and TNM are the tools that currently guide treatment decisions. Surgery is the only curative treatment, but relapse is common. After relapse or advanced staged disease survival is poor and systemic treatment has modestly improved survival. An association between sun exposure, vitamin D status and gastric cancer (GC) incidence and mortality has been reported. The molecular differences of the histological subtypes and the new molecular classifications account for the great heterogeneity of this disease and are the basis for the discovery of new therapeutic targets. New prognostic and predictive factors are essential and microRNAs (miRNAs) are endogenous small non-coding RNA molecules with a great potential for diagnosis, prognosis and treatment of cancer. There are hundreds of miRNAs with altered expression in tumor gastric tissue when compared to normal gastric tissue. Many of these miRNAs are associated with clinicopathological variables and survival in patients with GC. Furthermore, the expression of some of these miRNAs with prognostic importance in CG is influenced by vitamin D and others are mediators of some of the actions of this vitamin. This review aims to update the evidence on several miRNAs with prognostic value and therapeutic potential in GC, whose expression may be influenced by vitamin D or may regulate vitamin D signaling.

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers.

Gastric cancer (GC) is one of the most common and difficult diseases to treat. The study of signaling pathway regulation by microRNA provides information on the mechanisms of GC development and is the basis for biomarker creation. In this study, a circuit of microRNA interactions with signaling pathways was constructed. The microRNAs, associated with metastasis and chemoresistance, are described. In most cases, microRNAs in GC regulate the Wnt/β-catenin, PI3K/AKT/mTOR, RAS/RAF/ERK/MAPK, NF-kB, TGF-β, and JAK/STAT pathways. Part of the microRNA acts on several target genes that function in different pathways. This often leads to an intensification of the induced processes. MicroRNAs have also been described that have the opposite effect on different pathways, causing different functional consequences. By acting on several target genes, or genes associated with several pathways, microRNAs can function in a signaling network. MicroRNAs associated with metastasis most often interact with the Wnt/β-catenin pathway. MicroRNAs affecting chemoresistance, in most cases, affect the regulators of apoptosis and are associated with the PI3K/AKT/mTOR pathway. The characteristics of microRNAs proposed as candidates for GC biomarkers were analyzed. The currently developed diagnostic and prognostic panels of microRNAs are also considered.

Current perspectives on the dysregulated microRNAs in gastric cancer.

Since gastric cancer (GC) is diagnosed at advanced stages, the survival rate is low in affected people. In this regard, investigating the mechanisms underlying GC development, are so critical. MiRNAs, which are small non coding RNAs, as a post transcriptional repressor, regulate expression of target genes by stimulating breakage or transcription suppression of their targets therefore aberrant expression of miRNAs leading to GC carcinogenesis. In the last decades, there have been various studies approving the pivotal role of miRNAs in various phases of GC development including cancer initiation, proliferation, migration, invasion, metastasis, angiogenesis, apoptosis, and drug resistance. Therefore, the present review aimed at summarizing the dysregulated miRNAs which contribute to various cellular and developmental mechanisms such as, proliferation, apoptosis, invasion, migration, and angiogenesis. Moreover, it provides an overview on novel miRNAs involved in drug resistance and circular miRNAs as cancer biomarkers. Thereafter, it is hoped that the present study will shed more light on diagnostic and prognostic biomarkers of GC, and potential GC treatments based on miRNAs.

MicroRNAs in gastric cancer: Biomarkers and therapeutic targets.

MicroRNAs (miRNAs) are a group of non-coding RNAs that have critical roles in regulation of expression of genes. They can inhibit or decrease expression of target genes mostly via interaction with 3' untranslated region of their targets. Their crucial roles in the regulation of expression of tumor suppressor genes and oncogenes have potentiated them as contributors in tumorigenesis. Moreover, their stability in body fluids has enhanced their potential as cancer biomarkers. In the present review article, we describe the role of miRNAs in the pathogenesis of gastric cancer and advances in application of miRNAs as biomarkers and therapeutic targets in this kind of malignancy.

The Complex Network between MYC Oncogene and microRNAs in Gastric Cancer: An Overview.

Despite the advancements in cancer treatments, gastric cancer is still one of the leading causes of death worldwide. In this context, it is of great interest to discover new and more effective ways of treating this disease. Accumulated evidences have demonstrated the amplification of 8q24.21 region in gastric tumors. Furthermore, this is the region where the widely known MYC oncogene and different microRNAs are located. MYC deregulation is key in tumorigenesis in various types of tissues, once it is associated with cell proliferation, survival, and drug resistance. microRNAs are a class of noncoding RNAs that negatively regulate the protein translation, and which deregulation is related with gastric cancer development. However, little is understood about the interactions between microRNAs and MYC. Here, we overview the MYC role and its relationship with the microRNAs network in gastric cancer aiming to identify potential targets useful to be used in clinic, not only as biomarkers, but also as molecules for development of promising therapies.

MiR-1-3p suppresses cell proliferation and invasion and targets STC2 in gastric cancer.

MiR-1 has been reported to act as an inhibitory microRNA in gastric cancer (GC). This study aimed to investigate the regulatory mechanism by which miR-1-3p blocks the progression of GC by targeting stanniocalcin 2 (STC2). The expression level of miR-1-3p in GC was assessed via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Expressions of STC2 were measured by qRT-PCR and Western blot analysis. Proliferation and invasion assays were detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays, respectively. Moreover, the dual-luciferase reporter assay was used to confirm the binding sites between miR-1-3p and STC2. MiR-1-3p was significantly down-regulated in GC. Moreover, abnormal expression of miR-1-3p was correlated with GC tumor size. Functionally, overexpression of miR-1-3p inhibited proliferation and invasion in GC by inhibiting stanniocalcin 2 (STC2) expressions. In contrast, STC2 was significantly up-regulated in GC. Furthermore, miR-1-3p negatively regulated STC2 expression in GC. The upregulation of STC2 weakened the inhibitory effect of miR-1-3p in GC. MiR-1-3p suppressed cell proliferation and invasion by targeting STC2 in GC, providing a novel therapeutic target for GC.

MiR-497-5p inhibits gastric cancer cell proliferation and growth through targeting PDK3

MicroRNA plays an important role in gastric cancer (GC) development, while the function of miR-497-5p in this disease remains unknown. In the present study, we demonstrated miR-497-5p as a tumor suppressive microRNA in GC. miR-497-5p was down-regulated in GC tissues and its expression was associated with the disease stage. Inhibition of miR-497-5p promoted GC cell proliferation and growth. By contrast, miR-497-5p ectopic expression suppressed the proliferation and growth of GC cells. In addition, miR-497-5p inhibited DNA synthesis and enhanced apoptosis in GC cells. The cell cycle progression was suppressed by miR-497-5p. Mechanistically, miR-497-5p directly targeted and suppressed the expression of pyruvate dehydrogenase kinase 3 (PDK3), which is highly expressed in GC tissues. Over-expression of PDK3 promoted the proliferation of GC cells. Our study revealed that miR-497-5p inhibited GC cell proliferation and growth via targeting PDK3.

Scenario and future prospects of microRNAs in gastric cancer: A review.

Carcinoma of the stomach is one of the major prevalent and principal causes of cancer-related deaths worldwide. Current advancement in technology has improved the understanding of the pathogenesis and pathology of gastric cancers (GC). But, high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate novel early diagnostic/prognostic markers and therapeutic targets for GC, which are sufficiently sensitive to GC. Current biomedical investigations have explored several budding GC biomarker by utilizing serum proteins, natural oncogenic genes during improvement in molecular technologies as microarray, and RNA/DNA-Seq. Recently, small non-coding microRNAs (miRNAs) are becoming vital regulators in oncogenesis pathways and can act as handy clinical biomarkers. The newly introduced class of biomarkers is rising as new molecules for cancer diagnosis and prognosis. For better understanding of the gastric carcinogenesis, miRNAs may help to elucidate the mechanisms of tumor growth and can help to discover novel untimely potent markers for early detection of GC. Here in this review, we summarize the recent research studies supporting the utility of miRNAs as novel early diagnostic/prognostic tools and therapeutic targets. Thus, here we introduce potential future treatment strategies for gastrointestinal (GI) cancers, which indicate the practicality and clinical applications of miRNAs in GC.

Squaring the circle: sponging microRNAs in gastric cancer

We have known for some time that the instead of transcribing the roughly 2% of the genome that encodes for proteins, our cells transcribe approximately 75% of our genome (1). That equates to an awful lot of what we now call non-coding RNA (ncRNA). ncRNA itself can be loosely separated into two classes based on size: short ncRNAs (those shorter than 200 bases), and long ncRNAs (those greater than 200 bases) (2,3).

MicroRNAs in gastric cancer: from bench to bedside.

Gastric carcinogenesis results from complex interactions between host and environmental and bacterial factors, and this leads to genetic and epigenetic deregulation of oncogenic and tumor-suppressive genes. MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate almost 30% of human genes post transcriptionally and they are crucial in the initiation and progression of various diseases; especially malignancies. Accumulated evidence documents changes in gene sequences and epigenetic modifications. These then lead to abnormal miRNA expression in gastric cancer (GC) and also to deregulated miRNAs which act as oncogenes or tumor suppressors by regulating related target genes and contributing to malignant phenotypes. This altered miRNA expression in body fluids could well provide a novel biomarker for GC patient diagnosis and prognosis. MiRNAs present a promising target for GC treatment, and more tempting, for eradication of gastric cancer stem cells. This latter sub-group of tumor cells is thought to initiate and maintain GC development. Herein, we review the aberrant expression of miRNA expression and the underlying mechanisms and consequential effects of miRNA de-regulation. This identifies the responsible gastric cancer target genes, and highlights potential clinical applications.

Prognostic value of microRNAs in gastric cancer: a meta-analysis

BackgroundPrevious articles have reported that expression levels of microRNAs (miRNAs) are associated with survival time of patients with gastric cancer (GC). A systematic review and meta-analysis was performed to study the outcome of it.DesignMeta-analysis.MethodsEnglish studies estimating expression levels of miRNAs with any of survival curves in GC were identified up till March 19, 2017 through performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two authors independently. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS).ResultsSixty-nine relevant articles about 26 miRNAs with 6148 patients were ultimately included. GC patients with high expression of miR-20b (HR=2.38, 95%CI=1.16-4.87), 21 (HR=1.77, 95%CI=1.01-3.08), 106b (HR=1.84, 95%CI=1.15-2.94), 196a (HR=2.66, 95%CI=1.94-3.63), 196b (HR=1.67, 95%CI=1.38-2.02), 214 (HR=1.84, 95%CI=1.27-2.67) or low expression of miR-125a (HR=2.06, 95%CI=1.26-3.37), 137 (HR=3.21, 95%CI=1.68-6.13), 141 (HR=2.47, 95%CI=1.34-4.56), 145 (HR=1.62, 95%CI=1.07-2.46), 146a (HR=2.60, 95%CI=1.63-4.13), 206 (HR=2.85, 95%CI=1.73-4.70), 218 (HR=2.61, 95%CI=1.74-3.92), 451 (HR=1.73, 95%CI=1.19-2.52), 486-5p (HR=2.45, 95%CI=1.65-3.65), 506 (HR=2.07, 95%CI=1.33-3.23) have significantly poor OS (P<0.05).ConclusionsIn summary, miR-20b, 21, 106b, 125a, 137, 141, 145, 146a, 196a, 196b, 206, 214, 218, 451, 486-5p and 506 demonstrate significantly prognostic value. Among them, miR-20b, 125a, 137, 141, 146a, 196a, 206, 218, 486-5p and 506 are strong biomarkers of prognosis in GC.

MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer

BackgroundWe recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis.MethodsWe measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay.ResultsExpression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells.ConclusionsMiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy.

Prognostic value of candidate microRNAs in gastric cancer: A validation study.

Studies have reported the prognostic value of dysregulated microRNAs (miRNAs) in gastric cancer (GC). However, the results demonstrated so far are inconsistent. To better understand the miRNAs with prognostic relevance. Evaluable miRNAs were selected based on our selection criteria and further analyzed in formalin-fixed paraffin-embedded (FFPE) tissue samples of 169 GC patients using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 19 miRNAs were selected as candidate miRNAs. Among those miRNAs identified, high expression of miR-21-5p was related to poor overall survival (OS) and disease free survival (DFS) and was identified as an independent prognostic factor. Cases with high level of miR-200c-3p showed poor DFS. Subgroup analysis revealed that high expression of miR-21-5p and miR-222-3p was associated with poor OS and DFS in GC patients not received adjuvant chemotherapy. In male patients, high expression level of miR-21-5p was related to poor OS and DFS. The present study confirmed that elevated level of miR-21-5p could serve as an independent predictor for poor OS and DFS of GC patients. Moreover, miR-200c-3p, miR-222-3p might also play important roles in the prognosis of GC patients. Further studies are warranted to validate our findings and identify the functions and mechanisms of these miRNAs.

Circulating microRNA-196a/b are novel biomarkers associated with metastatic gastric cancer

miR-196a and/or miR-196b, involved in cancer initiation and progression, are frequently upregulated in tumour tissues. However, the clinical significance of these microRNAs in gastric cancer (GC) remains to be clarified. In the current study, we investigated the potential utility of circulating miR-196a/b as novel biomarkers for early detection and/or metastatic prognosis of GC. The quantitative real time-polymerase chain reaction data revealed markedly higher pre-operative circulating miR-196a and miR-196b levels in GC patients than healthy controls. Receiver-operating characteristics curve analysis showed that circulating miR-196a, miR-196b and combined miR-196a and miR-196b (miR-196a/b) are more effective than carcinoembryonic antigen or carbohydrate antigen 19-9 alone in distinguishing GC patients from healthy controls, with higher sensitivity and specificity. Circulating miR-196a exhibited higher diagnostic capacity than combined miR-196a/b or miR-196b alone, highlighting its potential as an effective plasma biomarker for GC. In clinicopathological analysis, elevated circulating miR-196a/b levels were highly correlated with metastatic potential or more advanced stages of disease and poorer survival. In addition, the expression levels of circulating miR-196a/b were reduced after surgical resection in GC patients. Taken together, we propose that circulating miR-196a/b serve as a more sensitive and specific novel biomarker than carbohydrate antigen 19-9 for GC monitor, diagnosis and prognosis.

MiR-429 functions as a tumor suppressor by targeting FSCN1 in gastric cancer cells.

It has been previously reported that the deregulation of microRNAs in gastric cancer (GC) was correlated with the progression and prognosis. miR-429, a member of the miR-200 family, was previously shown to play an important role in human carcinomas. Our study shows that miR-429 is significantly downregulated in GC tissues compared with matched nontumor tissues. Overexpression of miR-429 in GC cells suppressed cell proliferation. Fascin-1 (FSCN1) was identified as one of the targets of miR-429 and knockdown of FSCN1 mimics the function of miR-429 overexpression. In conclusion, miR-429 acts as a tumor suppressor by targeting FSCN1, suggesting that miR-429 and FSCN1 can both be potential therapeutic targets of GC.