• biomarker
• cancer diagnosis
• kidney cancer
• miRNA
• paraffin tissue
• renal cell carcinoma

• FSTL1
• adipogenesis
• inflammation
• miR-125a-3p
• preadipocytes

• Animals
• Mice
• Adipocytes/metabolism
• Adipogenesis/genetics
• MicroRNAs/metabolism
• Obesity/genetics
• Obesity/metabolism
• RNA, Messenger/metabolism

• Biomarkers
• Gastric adenocarcinoma
• Molecular signatures
• Peritoneal dissemination

• Humans
• Stomach Neoplasms/pathology
• Adenocarcinoma/pathology
• Peritoneal Neoplasms/pathology
• Peritoneal Neoplasms/secondary
• Peritoneal Neoplasms/surgery
• Prognosis

• Gastric Cancer
• Gastric disease
• Helicobacter pylori
• miRNA-125a-5p

• Adult
• Aged
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/metabolism
• Brazil/epidemiology
• Cell Line, Tumor
• Cell Proliferation
• Early Detection of Cancer/methods
• Female
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Gastritis/genetics
• Gastritis/microbiology
• Gastritis/pathology
• Gene Expression Profiling
• Genetic Predisposition to Disease
• Helicobacter Infections/epidemiology
• Helicobacter Infections/genetics
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/isolation & purification
• Humans
• Male
• MicroRNAs/analysis
• MicroRNAs/metabolism
• Middle Aged
• Prevalence
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/pathology

• ABT-199 (Venetoclax)
• ABT-263 (Navitoclax)
• B-Cell lymphoma 2 (BCL-2)
• DNA methylation
• DNA methyltransferase (DNMT)
• Dynamin-related protein 1 (Drp1)
• Group 1 pulmonary hypertension
• Hypoxia-inducible factor 1α (HIF-1α)
• Hypoxia-inducible factor 2α (HIF-2α)
• Hypoxic pulmonary vasoconstriction
• Mammalian target of rapamycin (mTOR)
• Mitochondrial calcium uniporter (MCU)
• Mitochondrial dynamics protein of 49 kDa (MiD49)
• Mitochondrial dynamics protein of 51 kDa (MiD51)
• Mitofusin 2 (Mfn2)
• Mitophagy
• Monocrotaline
• Oxygen sensing
• Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)
• Pyruvate dehydrogenase (PDH)
• Pyruvate dehydrogenase kinase (PDK)
• Pyruvate kinase muscle isoform 2 (PKM2)
• Reactive oxygen species (ROS)
• Sugen5416
• Survivin
• miR-138
• miR-25
• microRNA (miRNA)
• von hippel-lindau protein (VHL)

• Biology
• Humans
• Hydrogen Peroxide
• Hypertension, Pulmonary/genetics
• Neoplasms/genetics
• Neoplasms/therapy
• Oxygen

• R01 HL071115 NHLBI NIH HHS
• R01 HL113003 NHLBI NIH HHS
• RC1 HL099462 NHLBI NIH HHS

• angiogenesis
• circular RNAs
• gastrointestinal cancers
• long non-coding RNAs
• microRNAs
• non-coding RNAs

Radiation therapy is an effective method in the management of esophageal cancer. MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. However, the roles of specific miRNAs in radioresistant esophageal cancer remain to be investigated. In present study, the relative expression level of miR-20b-5p and miR-125a-5p were evaluated by quantitative Real-time polymerase chain reaction. Cell counting Kit-8 assay, wound-healing assay, transwell assay were used to assess cell proliferation, cell migration and cell invasion. TUNEL and Annexin V-FITC assays were applied to evaluate cell apoptosis. Dual-luciferase reporter gene assay was conducted to identify direct targets of miRNAs. The protein expression level was assessed by Western blot. The results indicated that miR-20b-5p was increased in radioresistant KYSE-150R cells compared with KYSE-150 cells, whereas miR-125a-5p was downregulated. MiR-20b-5p upregulation promoted cell proliferation, migration, invasion, and the EMT process, and decreased apoptosis by negatively regulating PTEN. MiR-125a-5p inhibited cell proliferation, migration, invasion, the EMT process and it induced apoptosis by negatively regulating IL6R. These data indicate that miR-20b-5p and miR-125a-5p promote tumorigenesis in radioresistant KYSE-150R cells and have the potential to be used as novel therapeutic targets for the treatment of esophageal cancer.

• esophageal cancer
• miR-125a-5p
• miR-20b-5p
• radiotherapy resistance
• tumorigenesis

The EGFR/HER2 signaling network is an effective therapeutic target for HER2-positive cancers, which are known for their aggressive biological course. Evidence indicates that the EGFR/HER2 network plays a role in the aggressive basal-like subtype as well. Here, we studied the potential role of miR-125a-3p as a modulator of the EGFR/HER2 pathway in basal-like breast cancer. Over-expression of miR-125a-3p reduced the migratory capability of MDA-MB-231 cells and led to an increase in the expression of ErbB2 transcript and protein. The induced ErbB2 responded to trastuzumab and underwent internalization and subsequent intra-lysosomal degradation. Trastuzumab treatment further reduced the migratory capability and induced the apoptosis of the cells. An in-vivo mouse model, which supported the in-vitro findings, showed a synergistic effect for miR-125a-3p and trastuzumab. Trastuzumab-treated miR-125a-3p-induced tumors were significantly smaller than control induced tumors. Our findings indicate that, in the basal-like subtype of breast cancer, miR-125a-3p may act as a tumor suppressor. miR-125a-3p induces an increase in the expression of ErbB2 that may render the cells suitable for treatment with anti-HER2 therapies.

• ErbB2
• TNBC
• apoptosis
• epigenetics
• miRNA
• migration

Translationally controlled tumor protein (TCTP) is linked to lung cancer. However, upon lung cancer carcinogens stimulation, there were no reports on the relationship between TCTP and lung cell carcinogenic epithelial–mesenchymal transition (EMT). This study was designed to investigate the molecular mechanism of regulation of TCTP expression and its role in lung carcinogens-induced EMT.

To study the role of TCTP in lung carcinogens [particulate matter 2.5 (PM_2.5) or 4-methylnitrosamino-l-3-pyridyl-butanone (NNK)]-induced EMT, PM_2.5/NNK-treated lung epithelial and non-small cell lung cancer (NSCLC) cells were tested. Cell derived xenografts, human lung cancer samples and online survival analysis were used to confirm the results. MassArray assay, Real-time PCR and Reporter assays were performed to elucidate the mechanism of regulation of TCTP expression. All statistical analyses were performed using GraphPad Prism version 6.0 or SPSS version 20.0.

Translationally controlled tumor protein and vimentin expression were up-regulated in PM_2.5/NNK-treated lung cells and orthotopic implantation tumors. TCTP expression was positively correlated with vimentin in human NSCLC samples. Patients with high expression of TCTP displayed reduced overall and disease-free survival. TCTP overexpression could increase vimentin expression and promote cell metastasis. Furthermore, PM_2.5/NNK stimulation brought a synergistic effect on EMT in TCTP-transfected cells. TCTP knockdown blocked PM_2.5/NNK carcinogenic effect. Mechanically, PM_2.5/NNK-induced TCTP expression was regulated by one microRNA, namely miR-125a-3p, but not by methylation on TCTP gene promoter. The level of TCTP was regulated by its specific microRNA during the process of PM_2.5/NNK stimulation, which in turn enhanced vimentin expression and played a permissive role in carcinogenic EMT.

Our results provided new insights into the mechanisms of TCTP regulatory expression in lung carcinogens-induced EMT. TCTP and miR-125a-3p might act as potential prognostic biomarkers and therapeutic targets for NSCLC.

• Epithelial–mesenchymal transition (EMT)
• Lung carcinogens PM2.5/NNK
• Translationally controlled tumor protein (TCTP)
• microRNA
• vimentin

• Breast cancer
• MTDH
• TP73-AS1
• malignant progression
• miR-125a

• Animals
• Apoptosis
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Cell Movement
• Cell Proliferation
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• In Vitro Techniques
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• Prognosis
• RNA, Long Noncoding/genetics
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays

• Dental caries
• Dental pulp stem cells (DPSCs)
• Fyn
• MicroRNA-125a-3p
• Odontoblastic differentiation

• TAZ
• colorectal neoplasm
• invasion
• miR-125
• proliferation

• Cell Movement/genetics
• Cell Proliferation/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Female
• Gene Expression Regulation, Neoplastic/genetics
• HCT116 Cells
• Humans
• Male
• MicroRNAs/genetics
• Neoplasm Invasiveness/genetics
• Neoplasm Invasiveness/pathology
• RNA, Small Interfering/genetics
• RNA, Small Interfering/pharmacology
• Trans-Activators/genetics
• Transcriptional Coactivator with PDZ-Binding Motif Proteins

microRNAs (miRs) serve critical roles in tumor progression. Low expression of miR-125a in gastric carcinoma (GC) may promote tumor development. In the present study, low expression of miR-125a was confirmed in cancer tissues using The Cancer Genome Atlas database. Additionally, the expression and clinical significance of miR-125a-5p was investigated using reverse transcription-quantitative PCR in 150 cases of GC. The results of the present study demonstrated that the level of miR-125a-5p expression was decreased in GC biopsies compared with that in matched adjacent normal tissues. Low expression of miR-125a-5p was associated with increased tumor diameter, high Ki67 expression and poor overall survival of patients with GC. Multivariate survival analysis demonstrated that low miR-125a-5p expression may be used as an independent prognostic factor for patients with GC. However, no effects on the cell viability in a Cell Counting kit-8 assay, and cell migration and invasion in Transwell assays were detected in response to treatment using miR-125a-5p mimics or inhibitors in vitro. Therefore, the results of the present study provide evidence that low expression of miR-125a-5p may be associated with a poor prognosis, suggesting its value as a tumor biomarker for patients with GC.

• The Cancer Genome Atlas
• gastric cancer
• microRNA-125a
• survival

• HULC
• Ovarian carcinoma
• PI3K/AKT/mTOR signaling pathway
• miR-125a-3p

• CASC9
• Nrg1
• cell migration
• hemangioma
• invasion
• miR-125a-3p

• VEGFA
• colorectal cancer
• miR-125a-5p
• overall survival

• biomarker
• diagnosis
• gastric cancer
• microRNA
• prognosis

Colorectal cancer is a commonly diagnosed malignancy and also the major cause of death worldwide. Chemotherapy is the primary therapy for advanced colorectal cancer. Although oxaliplatin has potential effect in colorectal cancer therapy, the molecular mechanisms involved in its cytotoxic effects are not well elucidated. This study outlines the regulatory effects of oxaliplatin on miRNAs expression in colon cancer cells and correlates it with the changing microRNA expression with p53 and p73 expression status in cells. HCT116^p53+/+ and HCT116^p53-/- cells were exposed to oxaliplatin, and the cellular viability was determined by XTT. p73 was knocked down using siRNA and the tumor cells were then treated with oxaliplatin. The expression profile of 384 miRNAs was determined by TaqMan® human miRNA array and calculated by the ∆∆C_t method. Cellular viability was found to decrease after the treatment with oxaliplatin in a dose-dependent manner. The wild-type p53 cells were found to be more sensitive than the null-p53 derivatives. A selective set of miRNAs were either up-regulated or down-regulated in response to the oxaliplatin treatment with a presumable role of p53 and p73 proteins. The miRNAs expression is known to influence the pharmacodynamic mechanisms of oxaliplatin and these effects have been observed to be regulated by p53 and p73. Our results may therefore provide more evidence for identifying a suitable biomarker for the diagnosis of colon cancer.

• Oxaliplatin
• colon cancer cells.
• miRNAs
• p53
• p73

In this study, with the aid of microarray technology, transmembrane protease serine 4 (TMPRSS4), a novel member of the serine protease family, was found to be upregulated in the majority of lung adenocarcinoma (LUAD) tissues compared to normal lung tissues. Of note, the clinical significance of TMPRSS4 in LUAD has not yet been reported, at least to the best of our knowledge. Through immunohistochemistry assays, we found that TMPRSS4 was overexpressed in LUAD tissues and that the TMPRSS4 expression level was also proportionally associated with the AJCC clinical stage, T stage and pathological grade. Moreover, a high expression of TMPRSS4 was found to be associated with adverse outcomes and was a significant independent factors predicting a poor prognosis. To elucidate the possible mechanisms responsible for the overexpression of TMPRSS4, we examined at microRNAs (miRNAs or miRs), which are small non-coding RNAs commonly dysregulated in human malignancies and are known to promote carcinogenesis by interacting with other types of RNAs. By means of bioinformatics analysis, a miRNA potentially targeting TMPRSS4 mRNA, namely miR-125a-5p, was selected. Dual luciferase reporter gene assays were then performed to verify the interaction. The results of MTT assays and apoptotic assays revealed that miR-125a-5p significantly inhibited cell growth and enhanced apoptosis, and the silencing of TMPRSS4 had similar effects. Furthermore, we observed that either the overexpression of miR-125a-5p or the silencing of TMPRSS4 prevented the activation of the nuclear factor (NF)-κB signaling pathway. On the whole, our findings illustrate that TMPRSS4 may be a candidate oncogene and may thus serve as a prognostic biomarker for LUAD, and its overexpression may be partly ascribed to the downregulation of miR-125a-5p. The dysregulation of miR-125a-5p and TMPRSS4 affect the biological function of LUAD cells via the NF-κB signaling pathway. The miR-125a-5p/TMPRSS4/NF-κB axis may thus provide novel insight into the pathogenic mechanisms of LUAD and may be used in the development of novel treatment strategies for LUAD.

Mitochondrial fission is important for the development and progression of pancreatic cancer (PC). However, little is known regarding its role in pancreatic cancer apoptosis, metabolism and migration. In the current study, the mechanism by which mitochondrial fission modifies the biological characteristics of PC was explored. MicroRNA-125a (miR-125a) had the ability to inhibit mitochondrial fission and contributed to cellular survival. Suppressed mitochondrial fission led to a reduction in mitochondrial debris, preserved the mitochondrial membrane potential, inhibited mitochondrial permeability transition pore opening, ablated cytochrome c leakage into the cytoplasm and reduced the pro-apoptotic protein contents, finally blocking mitochondria related apoptosis pathways. Furthermore, defective mitochondrial fission induced by miR-125a enhanced mitochondria-dependent energy metabolism by promoting activity of electron transport chain complexes. Furthermore, suppressed mitochondrial fission also contributed to PANC-1 cell migration by preserving the F-actin balance. Furthermore, mitofusin 2 (Mfn2), the key defender of mitochondrial fission, is involved in inhibition of miR125a-mediated mitochondrial fission. Low contents of miR-125a upregulated Mfn2 transcription and expression, leading to inactivation of mitochondrial fission. Ultimately, the current study determined that miR-125a and Mfn2 are regulated by hypoxia-inducible factor 1 (HIF1). Knockdown of HIF1 reversed miR-125a expression, and therefore, inhibited Mfn2 expression, leading to activation of mitochondrial fission. Collectively, the present study demonstrated mitochondrial fission as a tumor suppression process that is regulated by the HIF/miR-125a/Mfn2 pathways, acting to restrict PANC-1 cell survival, energy metabolism and migration, with potential implications for novel approaches for PC therapy.

Background: Resistance towards chemotherapy is a major obstacle in the treatment of esophageal squamous cell carcinoma (ESCC). We investigated the role of specific microRNAs in chemotherapy resistance and tumor biology. Methods: We selected three microRNAs from characteristic microRNA signatures of resistant ESCC (hsa-miR-125a-5p, hsa-miR-130a-3p, hsa-miR-1226-3p), and hsa-miR-148a-3p. Effects on chemotherapy, adhesion, migration, apoptosis and cell cycle were assessed in six ESCC cell lines. Target analyses were performed using Western blotting and luciferase techniques. Results: MiR-130a-3p sensitized cells towards cisplatin in 100% of cell lines, miR-148a-3p in 83%, miR-125a-5p in 67%, miR-1226-3p in 50% (p ≤ 0.04). MiR-130a-3p sensitized 83% of cell lines towards 5-FU, miR-148a-3p/miR-125a-5p/miR-1226-3p only 33% (p ≤ 0.015). Several resistance-relevant pathways seem to be targeted on various levels. Bcl-2 was confirmed as a direct target of miR-130a-3p and miR-148a-3p, and p53 as a target of miR-125a-5p. All microRNAs decreased migration and adhesion, except miR-130a-3p, and increased apoptosis. Simultaneous manipulation of two microRNAs exhibited additive sensitizing effects towards cisplatin in 50% (miR-125a-5p/miR-148a-3p), and 75% (miR-148a-3p/miR-130a-3p) of cell lines (p ≤ 0.006). Conclusion: Our data present strong evidence that specific microRNA signatures are responsible for drug resistance and aggressiveness of ESCC. Final functional readout of these complex processes appears to be more important than single microRNA-target interactions.

• K270: KYSE-270
• K410: KYSE-410
• chemotherapy
• esophageal squamous cell carcinoma
• metastasis
• miR: miRNA
• microRNA
• resistance

Previous studies have demonstrated that microRNAs (miRNAs/miRs) act as tumor suppressors or oncogenes during multiple processes in cancer. It has been observed that miR-27b may act as a tumor-suppressor and was significantly downregulated in a number of types of cancer. However, the functions of miR-27b in gastric cancer (GC) remain unclear. The present study aimed to investigate the functional role of miR-27b in the progression of GC. The downregulation of miR-27b in human GC plasma was confirmed using miRNA microarray and reverse transcription-quantitative polymerase chain reaction analyses. The association between circulating miR-27b expression and clinicopathological features of GC was analyzed and the results demonstrated that the level of circulating miR-27b was significantly correlated with GC differentiation. Receiver operating characteristic curve analysis identified that the plasma level of miR-27b may be a potential biomarker for differentiating patients with GC from healthy controls. In order to investigate the effect of miR-27b on GC cell behavior, miR-27b was overexpressed using miR-27b mimics, and it was observed that miR-27b was able to inhibit cell proliferation and induce apoptosis in SGC7901 cells. Previous studies have demonstrated that vascular endothelial growth factor C (VEGFC) is a target of miR-27b, and the results of the present study were consistent with these reports. Taken together, the results of the present study indicated that miR-27b may act as a potential biomarker for differentiating patients with GC from healthy controls, and serve as a tumor suppressor in GC by targeting VEGFC.

EphA2 is a crucial oncogene in gastric cancer (GC) development and metastasis, this study aims to identify microRNAs that target it and serve as key regulators of gastric carcinogenesis.

We identified several potential microRNAs targeting EphA2 by bioinformatics websites and then analyzed the role of miR-302b in modulating EphA2 in vitro and in vivo of GC, and it’s mechanism.

Our analysis identified miR-302b, a novel regulator of EphA2, as one of the most significantly downregulated microRNA (miRNA) in GC tissues. Overexpression of miR-302b impaired GC cell migratory and invasive properties robustly and suppressed cell proliferation by arresting cells at G0–G1 phase in vitro. miR-302b exhibited anti-tumor activity by reversing EphA2 regulation, which relayed a signaling transduction cascade that attenuated the functions of N-cadherin, β-catenin, and Snail (markers of Wnt/β-catenin and epithelial-mesenchymal transition, EMT). This modulation of EphA2 also had distinct effects on cell proliferation and migration in GC in vivo.

miR-302b serves as a critical suppressor of GC cell tumorigenesis and metastasis by targeting the EphA2/Wnt/β-catenin/EMT pathway.

The online version of this article (10.1186/s12885-017-3875-3) contains supplementary material, which is available to authorized users.

• EphA2
• Epithelial-mesenchymal transition
• Gastric cancer
• Wnt/β-catenin
• miR-302b

Pancreatic cancer, one of the top two most fatal cancers, is characterized by a desmoplastic reaction that creates a dense microenvironment, promoting hypoxia and inducing the epithelial-to-mesenchymal transition (EMT) to facilitate invasion and metastasis. Recent evidence indicates that the long noncoding RNA NORAD may be a potential oncogenic gene and that this lncRNA is significantly upregulated during hypoxia. However, the overall biological role and clinical significance of NORAD remains largely unknown.

NORAD expression was measured in 33 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of NORAD on pancreatic cancer cells were studied by overexpression and knockdown in vitro. Insights into the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatics analyses and luciferase assays. In vivo, metastatic potential was identified using an orthotopic model of PDAC and quantified using bioluminescent signals. Alterations in RhoA expression and EMT levels were identified and verified by immunohistochemistry and Western blotting.

NORAD is highly expressed in pancreatic cancer tissues and upregulated in hypoxic conditions. NORAD upregulation is correlated with shorter overall survival in pancreatic cancer patients. Furthermore, NORAD overexpression promoted the migration and invasion of pancreatic carcinoma cells, while NORAD depletion inhibited EMT and metastasis in vitro and in vivo. In particular, NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p, thereby promoting EMT.

Elevated expression of NORAD in pancreatic cancer tissues is linked to poor prognosis and may confer a malignant phenotype upon tumor cells. NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p. This finding may contribute to a better understanding of the role played by lncRNAs in hypoxia-induced EMT and provide a potential novel diagnostic and therapeutic target for pancreatic cancer.

The online version of this article (10.1186/s12943-017-0738-0) contains supplementary material, which is available to authorized users.

• cancer-associated fibroblasts
• epithelial-mesenchymal transition
• gastric cancer
• milky spots
• peritoneal dissemination

• disease-free survival
• hepatocellular carcinoma
• microR-125a
• overall survival
• risk factor

• AML
• TIM-3
• miR-125a-3p

• biomarker
• chemotherapy
• disease-free survival rate
• miR-125a-3p
• non-small cell lung cancer
• overall survival rate
• prognosis

• gastric cancer
• meta-analysis
• microRNA
• prognosis

• Gastric cancer
• SLC2A1
• glycolysis
• microRNA-148b

• Adenosine Triphosphate/metabolism
• Cell Line
• Cell Proliferation
• Down-Regulation
• Glucose/metabolism
• Glucose Transporter Type 1/genetics
• Glucose Transporter Type 1/metabolism
• Glycolysis
• Humans
• Lactic Acid/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Small Interfering/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

• DNA methylation
• epigenetic modulation
• gastric cancer
• histone modulation
• non-coding RNA

The mammalian transcriptome includes a large number of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Some studies have reported that numerous kinds of miRNAs and lncRNAs have been implicated in playing key regulatory roles in the occurrence and development of digestive system malignances. Therefore, they are closely related to the clinical diagnosis, treatment and prognosis of digestive system malignances. This review focuses on the recent progress in research of miRNAs and lncRNAs in in digestive system malignancies and discusses their epigenetics roles as oncogenes or tumor suppressors. The current and future potential clinical applications of miRNAs and lncRNAs in digestive system malignancies are also discussed, with an aim to provide new ideas and means for the diagnosis, treatment and prognosis of digestive system malignancies.

• miRNA
• lncRNA
• Digestive system malignancy
• Epigenetics
• Biomarker

• biomarker
• diagnosis
• gastric cancer
• microRNAs
• prognosis

• Animals
• Apoptosis
• Biomarkers, Tumor
• Cell Cycle/genetics
• Cell Proliferation
• Early Detection of Cancer
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• Neoplasm Metastasis
• Prognosis
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/mortality
• Stomach Neoplasms/therapy

Gastric cancer (GC) still keeps up high mortality worldwide with poor prognosis. Efficient and non-invasive prognostic biomarkers are urgently needed. MicroRNAs are non-coding RNAs playing roles in post-transcriptional gene regulation, which contribute to various biological processes such as development, differentiation and carcinogenesis. MicroRNA expression profiles have been associated with the prognosis and outcome in GC. MicroRNA prognostic biomarkers have been identified from blood or tissues samples, but with different prognostic features. Understanding the various roles of microRNAs in different sample sources of GC will provide deep insights into GC progression. In this review, we highlight the distinct prognostic roles of microRNAs biomarkers in blood and tissue according to their relationships with prognostic parameters, survival rates and target pathways. This will be useful for non-invasive biomarker development and selection in prognosis of GC.

• blood
• gastric cancer
• microRNA
• prognostic biomarker
• tissues

• AKT
• hepatocellular carcinoma
• invasion
• mammalian target of rapamycin
• microRNA-125a
• phosphoinositide 3-kinase

Orofacial inflammatory pain is a difficult clinical problem, and the specific molecular mechanisms for this pain remain largely unexplained. The present study aimed to determine the differential expression of microRNAs (miRNAs) and disclose the underlying role of miR-125a-3p in orofacial inflammatory pain induced by complete Freund's adjuvant (CFA). Thirty-two differentially expressed miRNAs were first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs) following CFA injection into the orofacial skin innervated by trigeminal nerve, and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and -299 were subsequently selected and validated by qPCR. The target genes were predicted based on the miRWalk website and were further analyzed by gene ontology (GO). Further studies revealed miR-125a-3p expression was down-regulated, whereas both the expression of p38 MAPK (mitogen-activated protein kinase) alpha and CGRP (calcitonin gene-related peptide) were up-regulated in ipsilateral TGs at different time points after CFA injection compared with control. Furthermore, mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene expression and is positively correlated with the head withdrawal threshold reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3′UTR of p38 alpha gene suppressed the transcriptional activity, and overexpression of miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells. Taken together, our results show that miR-125a-3p is negatively correlated with the development and maintenance of orofacial inflammatory pain via regulating p38 MAPK.

• Animals
• Base Sequence
• Behavior, Animal/drug effects
• Calcitonin Gene-Related Peptide/genetics
• Facial Pain/enzymology
• Facial Pain/genetics
• Facial Pain/metabolism
• Facial Pain/pathology
• Freund's Adjuvant/pharmacology
• Gene Ontology
• Inflammation/enzymology
• Inflammation/genetics
• Inflammation/metabolism
• Inflammation/pathology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Rats
• Rats, Sprague-Dawley
• Signal Transduction/drug effects
• Trigeminal Ganglion/drug effects
• Trigeminal Ganglion/enzymology
• Trigeminal Ganglion/metabolism
• Up-Regulation/drug effects
• Up-Regulation/genetics
• p38 Mitogen-Activated Protein Kinases/genetics

The protein encoded by the TP53 gene is one of the most important suppressors of tumor formation, which is also frequently inactivated in gastrointestinal cancer. MicroRNAs (miRNAs) are small noncoding RNAs that inhibit translation and/or promote degradation of their target messenger RNAs. In recent years, several miRNAs have been identified as mediators and regulators of p53’s tumor suppressing functions. p53 induces expression and/or maturation of several miRNAs, which leads to the repression of critical effector proteins. Furthermore, certain miRNAs regulate the expression and activity of p53 through direct repression of p53 or its regulators. Experimental findings indicate that miRNAs are important components of the p53 network. In addition, the frequent genetic and epigenetic alterations of p53-regulated miRNAs in tumors indicate that they play an important role in cancer initiation and/or progression. Therefore, p53-regulated miRNAs may represent attractive diagnostic and/or prognostic biomarkers. Moreover, restoration of p53-induced miRNAs results in suppression of tumor growth and metastasis in mouse models of cancer. Thus, miRNA-based therapeutics may represent a feasible strategy for future cancer treatment. Here we summarize the current published state-of-the-art on the role of the p53-miRNA connection in gastrointestinal cancer.

• cancer
• gastrointestinal tract
• microRNA
• p53

• Wnt-pathway
• juvenile angiofibroma
• microRNA
• β-catenin

Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many biological processes (e.g., cell proliferation, differentiation, apoptosis, invasion and development) through gene repression. Deregulation of miRNA expression in gastric tumors and cancer cell lines have been documented to contribute in tumorigenesis, and the expression signature may correlate with different cancer types and clinicopathological features. Here, we summarized the updated gastric cancer-associated miRNAs and the downstream targets in the process of tumorigenesis. Recently, many researchers make use of the miRNA microarray platform to profile miRNA expression in gastric cancer and correlated with different clinical parameters. Its application on cancer diagnosis, prognosis and predicting treatment response rate are still underway and needs further investigation. Emerging roles of miRNAs with oncogenic or tumor suppressive properties in gastric tumorigenesis were discussed. Epigenetic silencing of miRNA by hypermethylation of promoter CpG island was also observed in gastric cancer. However, detailed mechanisms of how miRNAs regulate gene expression in gastric cancer has not been well studied. In this review, we highlight the up-to-date findings on the deregulated miRNAs in gastric cancer, and the potential use of miRNA in the clinical settings, such as diagnostic/prognostic markers and chemotherapeutic tools.

• MicroRNA
• Gastric cancer
• Biomarker
• Diagnosis
• Prognosis
• Clinical application

• Animals
• Antineoplastic Agents/therapeutic use
• Apoptosis/drug effects
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Cell Proliferation/drug effects
• Drug Design
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Molecular Targeted Therapy
• Neoplasm Invasiveness
• Predictive Value of Tests
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology

Although gastric cancer (GC) is one of the leading causes of cancer-related death, major therapeutic advances have not been made, and patients with GC still face poor outcomes. The prognosis of GC also remains poor because the molecular mechanisms of GC progression are incompletely understood. MicroRNAs (miRNAs) are noncoding RNAs that are associated with gastric carcinogenesis. Studies investigating the regulation of gene expression by miRNAs have made considerable progress in recent years, and abnormalities in miRNA expression have been shown to be associated with the occurrence and progression of GC. miRNAs contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors, affecting cell proliferation, apoptosis, motility, and invasion. Moreover, a number of miRNAs have been shown to be associated with tumor type, tumor stage, and patient survival and therefore may be developed as novel diagnostic or prognostic markers. In this review, we discuss the involvement of miRNAs in GC and the mechanisms through which they regulate gene expression and biological functions. Then, we review recent research on the involvement of miRNAs in GC prognosis, their potential use in chemotherapy, and their effects on Helicobacter pylori infections in GC. A greater understanding of the roles of miRNAs in gastric carcinogenesis could provide insights into the mechanisms of tumor development and could help to identify novel therapeutic targets.

• MicroRNA
• Gastric cancer
• Reverse transcription-polymerase chain reaction
• Chemosensitivity
• Helicobacter pylori
• Circulating MicroRNA

• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/metabolism
• Disease Progression
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Helicobacter Infections/microbiology
• Helicobacter pylori
• Humans
• MicroRNAs/metabolism
• Prognosis
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

Fyn kinase is implicated in prostate cancer. We illustrate the role of miR-125a-3p in cellular pathways accounted for motility and migration of prostate cancer cells, probably through its regulation on Fyn expression and Fyn-downstream proteins. Prostate cancer PC3 cells were transiently transfected with empty miR-Vec (control) or with miR-125a-3p. Overexpression of miR-125a-3p reduced migration of PC3 cells and increased apoptosis. Live cell confocal imaging indicated that overexpression of miR-125a-3p reduced the cells' track speed and length and impaired phenotype. Fyn, FAK and paxillin, displayed reduced activity following miR-125a-3p overexpression. Accordingly, actin rearrangement and cells' protrusion formation were impaired. An inverse correlation between miR-125a-3p and Gleason score was observed in human prostate cancer tissues. Our study demonstrated that miR-125a-3p may regulate migration of prostate cancer cells.

• EMT
• Fyn
• actin cytoskeleton
• live imaging
• miR-125a-3p
• migration
• prostate cancer

• Base Sequence
• Carcinoma
• Cell Line, Tumor
• Gene Expression Profiling
• Gene Regulatory Networks
• Genomics
• High-Throughput Nucleotide Sequencing
• Humans
• MicroRNAs/genetics
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms/genetics
• Nasopharyngeal Neoplasms/pathology
• Radiation Tolerance/genetics
• Sequence Analysis, RNA

• biomarker
• exosome
• gastric cancer
• miRNA
• plasma
• serum