• Exosomes
• Gastric cancer
• Hepatocellular carcinoma
• Liver metastasis

• Biomarker
• Gastric cancer
• Liquid biopsy

• 2017R1A5A2015541 National Research Foundation of Korea

• Circulating tumor DNA
• Circulating tumor cells
• Exosomes
• Gastric cancer
• Liquid biopsy
• Non-coding RNAs

• Cell cycle genes
• Chromosomal instability
• Gastric cancer
• Genetic variation
• MiR-23b-5p

• P1-390 Javna Agencija za Raziskovalno Dejavnost RS
• Young Researcher Grant

Short-stranded miRNAs are single-stranded RNA molecules involved in the regulation of gene expression. miRNAs are involved in a variety of cellular physiological processes, including cell proliferation, differentiation, and apoptosis. miR-23b have been identified to act both as oncogenes and as tumor suppressors. In addition, miR-23b is related to inflammation resistance to various autoimmune diseases and restrained inflammatory cell migration. The characterization of the specific alterations in the patterns of miR-23b expression in cancer and autoimmune disease has great potential for identifying biomarkers for early disease diagnosis, as well as for potential therapeutic intervention in various diseases. In this review, we summarize the ever-expanding role of miR-23b and its target genes in different models and offer insight into how this multifunctional miRNA modulates tumor cell proliferation and apoptosis or inflammatory cell activation, differentiation, and migration.

• biomarkers
• diagnosis
• gastric cancer
• literature review
• prognosis
• sensitivity
• treatment

• GAS5
• HCC
• ddPCR
• miR-126-3p
• miR-23b-3p
• sorafenib

• CIB_2020 Consorzio Interuniversitario Biotecnologie
• AS-2018 FFRB
• eulo_2019 Fondazione Ente Universitario Lombardia Orientale
• IG_2018 Ricerchiamo Onlus

Emerging studies have noted that dysregulated lncRNAs are implicated in cancer progression and tumorigenesis. We first showed that MSC-AS1 was overexpressed in gastric cancer (GC) cells (HGC-27, MKN-45, SGC-7901 and MGC-803 cells) compared with GES cells. We observed that MSC-AS1 was upregulated in GC specimens compared with paired normal specimens. MSC-AS1 increased cell growth and cycle progression. Moreover, the overexpression of MSC-AS1 enhanced the secretion of the inflammatory mediators IL-1β, IL-6 and TNF-α. We found that the overexpression of MSC-AS1 inhibited the expression of miR-142-5p in HGC-27 cells. We noted that DDK5 was a target gene of miR-142-5p. The overexpression of miR-142-5p suppressed the luciferase activity of wild-type DDX5, but the luciferase activity of the mutant DDX5 was not changed. We showed that miR-142-5p was downregulated in GC specimens compared with paired normal specimens. MSC-AS1 expression was inversely correlated with miR-142-5p expression in GC specimens. MSC-AS1 induced cell growth, cell cycle progression and inflammatory mediator secretion by modulating DDX5. These results showed that MSC-AS1 functions as a key oncogene in the development of GC.

• DDX5
• MSC-AS1
• gastric cancer
• miR-142-5p

• HOXA3
• LINC00689
• gastric cancer
• miR-338-3p

Circulating microRNAs (miRNA) are small noncoding RNA molecules that can be detected in bodily fluids without the need for major invasive procedures on patients. miRNAs have shown great promise as biomarkers for tumors to both assess their presence and to predict their type and subtype. Recently, thanks to the availability of miRNAs datasets, machine learning techniques have been successfully applied to tumor classification. The results, however, are difficult to assess and interpret by medical experts because the algorithms exploit information from thousands of miRNAs. In this work, we propose a novel technique that aims at reducing the necessary information to the smallest possible set of circulating miRNAs. The dimensionality reduction achieved reflects a very important first step in a potential, clinically actionable, circulating miRNA-based precision medicine pipeline. While it is currently under discussion whether this first step can be taken, we demonstrate here that it is possible to perform classification tasks by exploiting a recursive feature elimination procedure that integrates a heterogeneous ensemble of high-quality, state-of-the-art classifiers on circulating miRNAs. Heterogeneous ensembles can compensate inherent biases of classifiers by using different classification algorithms. Selecting features then further eliminates biases emerging from using data from different studies or batches, yielding more robust and reliable outcomes. The proposed approach is first tested on a tumor classification problem in order to separate 10 different types of cancer, with samples collected over 10 different clinical trials, and later is assessed on a cancer subtype classification task, with the aim to distinguish triple negative breast cancer from other subtypes of breast cancer. Overall, the presented methodology proves to be effective and compares favorably to other state-of-the-art feature selection methods.

• TNBC
• circulating
• feature selection
• machine learning
• miRNAs

Background: Reports regarding liquid biopsy and gastric cancer (GC) have emerged rapidly in recent decades, yet their prognostic value still remains controversial. This study was aimed to assess the impact of liquid biopsy, including circulating tumor cells (CTCs) and cell-free nucleic acids, on GC patients' prognosis.

Methods: PubMed, Medline, EMBASE, and ClinicalTrial.gov databases were searched for studies that report GC patient survival data stratified by CTC/circulating tumor DNA (ctDNA)/circulating miRNAs' status. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for patients' overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were recorded or calculated depending on circulating target status.

Results: We initially identified 4,221 studies, from which 43 were eligible for further analysis, comprising 3,814 GC patients. Pooled analyses showed that detection of certain CTCs, ctDNA, and circulating miRNA was associated with poorer OS (CTCs: HR = 1.84, 95%CI 1.50–2.26, p < 0.001; ctDNA: HR = 1.78, 95%CI 1.36–2.34, p < 0.001; circulating miRNA: HR = 1.74, 95%CI 1.13–2.69, p < 0.001) and DFS/PFS (CTCs: HR = 3.39, 95%CI 2.21–5.20, p < 0.001; ctDNA: HR = 2.38, 95%CI 1.31–4.32, p = 0.004; circulating miRNA: HR = 3.30, 95%CI 2.39–4.55, p < 0.001) of GC patients, regardless of disease stage and time point at which sample is taken (at baseline or post-treatment).

Conclusions: The presence of CTCs and/or cellular components identifies a group of GC with poorer prognosis. Among circulating markers, CTCs demonstrated a stronger and more stable predictive value for late-stage disease and among Mongolian populations with GC. Less data are available for ctDNA and miRNA; however, their presence may also reflect aggressive biology and warrants further prospective study.

• circulating mRNA
• circulating tumor DNA
• circulating tumor cells
• gastric cancer
• liquid biopsy
• prognosis

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an abundant nuclear-localized long noncoding RNA (lncRNA) that has significant roles in cancer. While the interacting partners and evolutionary sequence conservation of MALAT1 have been examined, much of the structure of MALAT1 is unknown. Here, we propose a hypothetical secondary structural model for 8425 nucleotides of human MALAT1 using three experimental datasets that probed RNA structures in vitro and in various human cell lines. Our model indicates that approximately half of human MALAT1 is structured, forming 194 helices, 13 pseudoknots, five structured tetraloops, nine structured internal loops, and 13 intramolecular long-range interactions that give rise to several multiway junctions. Evolutionary conservation and covariation analyses support 153 of 194 helices in 51 mammalian MALAT1 homologs and 42 of 194 helices in 53 vertebrate MALAT1 homologs, thereby identifying an evolutionarily conserved core that likely has important functional roles in mammals and vertebrates. Data mining revealed that RNA modifications, somatic cancer-associated mutations, and single-nucleotide polymorphisms may induce structural rearrangements that sequester or expose binding sites for several cancer-associated microRNAs. Our findings reveal new mechanistic leads into the roles of MALAT1 by identifying several intriguing structure–function relationships in which the dynamic structure of MALAT1 underlies its biological functions.

• MALAT1
• cancer
• long noncoding RNA
• m6A
• secondary structure

• LINC00994
• gastric cancer
• lncRNAs
• miR-765-3p

• micrornas
• gc
• circulation
• meta-analysis
• biomarker

• Biomarkers, Tumor/genetics
• Circulating MicroRNA/genetics
• Humans
• Neoplasm Staging
• Odds Ratio
• Prospective Studies
• Sensitivity and Specificity
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics

• BTG1
• DGCR5
• PTEN
• gastric cancer
• miR-23b
• progression

Long noncoding RNAs (lncRNAs) were identified as potential regulatory factor in vascular disease. However, the role of XR007793 in the regulation of neointima formation after vascular injury remains largely unknown.

LncRNA expression levels were detected using real-time polymerase chain reaction (RT-PCR). In vivo and in vitro assay were performed in Sprague-Dawley rats and VSMCs. Cell Counting Kit-8 (CCK-8) assay, Transwell assay, and scratch wound healing assay were performed to detect cell proliferation and migration. Western blotting was used to detect protein expression.

The results of qRT-PCR indicated that XR007793 expression was significantly increased in the injured carotid artery of Sprague-Dawley rats and platelet-derived growth factor-BB induced rat aortic smooth muscle cells. Knockdown of XR007793 repressed the proliferation and migration of VSMC in vitro. The expression level of miR-23b was reduced in mouse carotid injured tissues and cell line. Bioinformatics analysis and luciferase reporter assay revealed that XR007793 directly bonds to miR-23b. Pearson correlation analysis showed that XR007793a and miR-23b were negatively correlated in carotid samples. Furthermore, bioinformatics analysis and luciferase assay indicated that miR-23b targeted the Forkhead box O 4 (FOXO4) 3′-UTR to inhibit FOXO4 expression. After transfecting miR-23b inhibitor, the expression both of XR007793 and FOXO4 was increased. The effects on expression were reversed after transfected with miR-23b mimics. Rescue experiments results indicated that miR-23b inhibitor reduced the expression of VSMC marker and promoted proliferation and migration of VSMC.

This study shows that XR007793 aggravates the loss of function of VSMCs by negatively regulating miR-23b. It does so by targeting FOXO4, which could serve as a novel therapeutic target in post-angioplasty restenosis.

Non-invasive diagnostic biomarkers may contribute to an early identification of gastric cancer (GC) and improve the clinical management. Unfortunately, no sensitive and specific screening biomarkers are available yet and the currently available approaches are limited by the nature of the disease. GC is a heterogenic disease with various distinct genetic and epigenetic events that occur during the multifactorial cascade of carcinogenesis. MicroRNAs (miRNAs) are commonly deregulated in gastric mucosa during the Helicobacter pylori infection and in stepwise manner from chronic gastritis, through preneoplastic conditions such as atrophic gastritis and intestinal metaplasia, to early dysplasia and invasive cancer. Identification of miRNAs in blood in 2008 led to a great interest on miRNA-based diagnostic, prognostic biomarkers in GC. In this review, we provide the most recent systematic review on the existing studies related to miRNAs as diagnostic biomarkers for GC. Here, we systematically evaluate 75 studies related to differential expression of circulating miRNAs in GC patients and provide novel view on various heterogenic aspects of the existing data and summarize the methodological differences. Finally, we highlight several important aspects crucial to improve the future translational and clinical research in the field.

• MicroRNA
• Biomarkers
• Screening
• Stomach
• Gastric cancer
• Systematic review
• Blood
• Serum
• Plasma

• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Carcinogenesis/genetics
• Circulating MicroRNA/blood
• Circulating MicroRNA/genetics
• Circulating MicroRNA/metabolism
• Early Detection of Cancer/methods
• Early Detection of Cancer/trends
• Gastric Mucosa/pathology
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Humans
• Precancerous Conditions/genetics
• Precancerous Conditions/pathology
• Stomach Neoplasms/blood
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics

• biomarker
• diagnosis
• gastric cancer
• microRNA
• prognosis

• Biomarker
• DNA methylation
• gastric cancer
• long noncoding RNA
• microRNA

The present study aimed to investigate the expression levels of microRNA (miR)-23a and miR-23b in the tumor tissues of patients with ovarian cancer. The study also explored the correlation of miR-23a and miR-23b expression levels in the tumor tissues with the clinic-pathological parameters and prognosis of the patients. Specimens of frozen tumor tissues and normal tissues adjacent to the tumor were collected from 50 patients with ovarian cancer. Reverse transcription-quantitative polymerase chain reaction was adopted to detect the expression levels of miR-23a and miR-23b in tumor tissues. Furthermore, normal tissues adjacent to the tumor were utilized as the control for the experiments and Pearson method was used to analyze the correlation between miR-23a and miR-23b expression levels in tumor tissues. The correlation of miR-23a and miR-23 expression in tumor tissues and the prognosis of the patients with ovarian cancer was analyzed in combination with clinical data. The expression of miR-23a in the tissues of ovarian cancer was significantly higher in comparison with normal adjacent tissues. However, the expression of miR-23b in the tissues of ovarian cancer was significantly lower when compared with adjacent normal tissues. Notably, the expression of miR-23a was negatively correlated with that of miR-23b in tumor tissues of ovarian cancer. The high expression of miR-23a and the low expression of miR-23b in tumor tissues of the patients was correlated with the degree of tumor differentiation, metastasis of lymph nodes and clinical staging. The five-year overall survival rate of the patients was 36% (18/50). Univariate survival analysis indicated that miR-23a and miR-23b were the factors influencing the overall survival rate of ovarian cancer. The present findings suggest that high expression of miR-23a and the low expression of miR-23b are closely correlated with the occurrence and development of ovarian cancer. The abnormal expression of the miR-23a and miR-23b could be utilized as potential prognostic molecular markers of ovarian cancer.

• microRNA-23a
• microRNA-23b
• ovarian cancer
• prognosis

• micrornas
• rna, long noncoding
• stomach neoplasms

• Computational Biology
• Databases, Genetic
• Disease Progression
• Gene Expression Regulation, Neoplastic/genetics
• Gene Regulatory Networks/genetics
• Humans
• MicroRNAs/genetics
• MicroRNAs/physiology
• Prognosis
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/physiology
• Stomach Neoplasms/genetics
• Survival Analysis

• PDE7A
• colon cancer
• invasion
• miR-23b
• migration

• gastric cancer
• meta-analysis
• microRNA
• prognosis

• Gastric cancer (GC)
• MiR-16
• MiR-451
• Prognosis

• Adenocarcinoma/diagnosis
• Adenocarcinoma/genetics
• Adenocarcinoma/mortality
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• MicroRNAs/genetics
• Middle Aged
• Prognosis
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/mortality
• Survival Analysis