• lung cancer
• microRNAs
• particulate matter
• polycyclic aromatic hydrocarbons
• pulmonary cancer

• Humans
• Polycyclic Aromatic Hydrocarbons/toxicity
• Polycyclic Aromatic Hydrocarbons/analysis
• MicroRNAs/genetics
• Air Pollutants/analysis
• Environmental Monitoring
• Lung Neoplasms/genetics
• Environmental Exposure/adverse effects
• Environmental Exposure/analysis
• Biomarkers
• Inflammation/genetics
• Particulate Matter/analysis

• VIPUCT-2022REG-PL-02 and VIPUCT 2023 FIAS-PL-03 This research was funded by VIPUCT-2022REG-PL-02 and VIPUCT 2023 FIAS-PL-03 grants from the Vicerrectoría de Investigación y Postgrado, Universidad Católica de Temuco.

• Cancer
• Diagnosis
• MiR-136–5p
• Prognosis

Gastric cancer (GC) is regarded as the most prevalent malignancy with the high mortality rate, worldwide. However, gastroscopy, a biopsy of suspected sample, and detecting CEA, CA19-9, and CA72-4 are presently used, but these diagnostic approaches have several limitations. Recently, microRNAs as the most important member of noncoding RNAs (ncRNAs) have received attention; recent evidence demonstrates that they can be used as the promising candidate biomarkers for GC diagnosis. We aimed to investigate the association between the microRNA-29a, -101, and -103 expression and autotaxin (ATX) and lysophosphatidic acid receptor 2 (LPA2) expression in GC patients. Material and Methods. The present study was conducted on 40 paired samples of primary GC tissue and adjacent noncancerous tissue. The gene expression levels of miR-101, -103, -29, ATX, and LPA2 were analyzed by quantitative reverse-transcription PCR (qRT-PCR). Besides, the protein levels of ATX and LPA2 were evaluated using western blot.

The expression levels of miR-29 and miR-101 were significantly lower (p value < 0.0001), but the miR-103 and LPA2 were significantly higher in gastric tumor samples compared to the corresponding nontumor tissues (p value < 0.0001). Moreover, the diagnostic accuracy of miRs to discrimine the GC patients from noncancerous controls was reliable (miR-101, sensitivity: 82.5% and specificity: 85%; miR-103, sensitivity: 72.5% and specificity: 90%; miR-29, sensitivity: 77.5% and specificity: 70%).

It seems that determining the expression level of miR-101, -103, and -29, as the novel diagnostic biomarkers, has diagnostic value to distinguish GC patients from healthy individuals.

As explorations deepen, the role of microRNAs (miRNAs) in lung squamous cell carcinoma (LUSC), from its emergence to metastasis and prognosis, has elicited extensive concern. LUSC-related miRNA and mRNA samples were acquired from The Cancer Genome Atlas (TCGA) database. The data were initially screened and pretreated, and the R platform and series analytical tools were used to identify the specific and sensitive biomarkers. Seven miRNAs and 15 hub genes were found to be closely related to the overall survival of patients with LUSC. Determination of the expression of these miRNAs can help improve the overall survival of LUSC patients. The 15 hub genes correlated with overall survival (OS). The new miRNA markers were identified to predict the prognosis of LUSC. The findings of this study offer novel views on the evolution of precise cancer treatment approaches with high reliability.

• Biomarkers, Tumor/genetics
• Carcinoma, Non-Small-Cell Lung/diagnosis
• Carcinoma, Non-Small-Cell Lung/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Lung/pathology
• Lung Neoplasms/diagnosis
• Lung Neoplasms/genetics
• MicroRNAs/genetics
• Prognosis
• Reproducibility of Results

• NASH
• biliary tract cancer
• bladder cancer
• breast cancer
• cancer
• cervical cancer
• demyelinating diseases
• endometrial cancer
• gastrointestinal cancer
• glioblastoma
• gynecological cancers
• hematological diseases
• hepatocellular carcinoma
• lung cancer
• melanoma
• miR
• miR therapeutics
• miR-221
• miR-221/222
• miRs
• microRNA
• myeloma
• neuropathy
• ovarian cancer
• pancreatic cancer
• pharmacokinetics
• prostate cancer
• renal cell carcinoma
• sarcomas
• solid cancers
• urogenital cancer

Gastric cancer (GC) is one of the most common malignancies in the world. It is also the fifth most common cancer in China. In recent years, a large number of studies have proved that non-coding RNAs (ncRNAs) can regulate cell proliferation, invasion, metastasis, apoptosis, and angiogenesis. NcRNAs also influence the therapeutic resistance of gastric cancer. NcRNAs mainly consist of miRNAs, lncRNAs and circRNAs. In this paper, we summarized ncRNAs as biomarkers and therapeutic targets for gastric cancer, and also reviewed their role in clinical trials and diagnosis. We sum up different ncRNAs and related moleculars and signaling pathway in gastric cancer, like Bcl-2, PTEN, Wnt signaling. In addition, the potential clinical application of ncRNAs in overcoming chemotherapy and radiotherapy resistance in GC in the future were also focused on.

• gastric cancer
• lncRNA
• microRNA
• non-coding RNA
• therapy resistance

Resistance against conventional chemotherapeutic agents is one of the main reasons for tumor relapse and poor clinical outcomes in cancer patients. Various mechanisms are associated with drug resistance, including drug efflux, cell cycle, DNA repair and apoptosis. Doxorubicin (DOX) is a widely used first-line anti-cancer drug that functions as a DNA topoisomerase II inhibitor. However, DOX resistance has emerged as a large hurdle in efficient tumor therapy. Furthermore, despite its wide clinical application, DOX is a double-edged sword: it can damage normal tissues and affect the quality of patients’ lives during and after treatment. It is essential to clarify the molecular basis of DOX resistance to support the development of novel therapeutic modalities with fewer and/or lower-impact side effects in cancer patients. Long non-coding RNAs (lncRNAs) have critical roles in the drug resistance of various tumors. In this review, we summarize the state of knowledge on all the lncRNAs associated with DOX resistance. The majority are involved in promoting DOX resistance. This review paves the way to introducing an lncRNA panel marker for the prediction of the DOX response and clinical outcomes for cancer patients.

• Cancer
• Chemotherapy
• Doxorubicin
• Drug resistance

• miR‑222‑3p
• biomarker
• cell signaling pathway
• exosome
• therapeutic target

• Biomarkers, Tumor/genetics
• Drug Resistance, Neoplasm
• Early Detection of Cancer
• Humans
• MicroRNAs/genetics
• Neoplasms/diagnosis
• Neoplasms/drug therapy
• Neoplasms/genetics
• Prognosis
• Survival Analysis

• PTEN
• PTENP1
• ceRNA
• cervical cancer
• miR-106b

• gastric cancer
• gastric inflammation
• gastric metaplasia
• helicobacter felis
• interferon-alpha

• Cancer Progression
• LNM
• Prognosis
• Prognostic Factor

• Extracellular vesicles
• GRHL2
• Gastric cancer
• M2 macrophages
• MLL3
• microRNA-130b-3p

• Bmi-1
• Gastric cancer
• RKIP
• miR-155
• miR-27a

• Animals
• Apoptosis
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Cell Movement
• Cell Proliferation
• Drug Resistance, Neoplasm
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• Neoplasm Metastasis
• Phosphatidylethanolamine Binding Protein/genetics
• Phosphatidylethanolamine Binding Protein/metabolism
• Polycomb Repressive Complex 1/genetics
• Polycomb Repressive Complex 1/metabolism
• Prognosis
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Survival Rate
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays

• National Natural Science Foundation of China
• Medical Science Foundation of Sun Yat-sen University
• Guangdong Science and Technology Department (CN)
• Guangdong Basic and Applied Basic Research Foundation

Immune escape is an immunological mechanism underlying tumorigenesis, and T cells play an important role in this process. In this study, immune-related genes were evaluated in tumor-infiltrating CD4⁺ and CD8⁺ T cells in colon cancer.

ESTIMATE was used to calculate stromal and immune scores for tumor datasets downloaded from The Cancer Genome Atlas–Colon Cancer (COAD). Differentially expressed genes (DEGs) between samples with high and low stromal and immune scores were screened, followed by a functional enrichment analysis of the overlapping DEGs. The DEGs related to CD4⁺ and the CD8⁺ T cells were then screened. Predicted miRNA–mRNA and lncRNA–miRNA pairs were used to construct a competing endogenous RNA (ceRNA) network. Furthermore, chemical–gene interactions were predicted for genes in the ceRNA network. Kaplan–Meier survival curves were also plotted.

In total, 83 stromal-related DEGs (5 up-regulated and 78 down-regulated) and 1270 immune-related DEGs (807 up-regulated and 293 down-regulated genes) were detected. The 79 overlapping DEGs were enriched for 39 biological process terms. Furthermore, 79 CD4⁺ T cell-related genes and 8 CD8⁺ T cell-related genes, such as ELK3, were screened. Additionally, ADAD1 and DLG3, related to CD4⁺ T cells, were significantly associated with the prognosis of patients with colon cancer. The chr22-38_28785274–29,006,793.1–miR-106a-5p-DDHD1 and chr22-38_28785274–29,006,793.1–miR-4319-GRHL1 axes obtained from CD4⁺ and CD8⁺ T cell-related ceRNAs were identified as candidates for further studies.

ELK3 is a candidate immune-related gene in colon cancer. The chr22-38_28785274–29,006,793.1–miR-106a-5p-DDHD1 and chr22-38_28785274–29,006,793.1–miR-4319-GRHL1 axes may be related to CD4⁺ and CD8⁺ T cell infiltration in colon cancer.

• CD4+ T cells
• CD8+ T cells
• Colon cancer
• Competing endogenous RNAs
• Immunity

It is generally accepted that microRNA-20a (miR-20a) is aberrantly expressed in gastrointestinal cancer (GIC), and may be associated with the prognosis of GIC patients. Nevertheless, the clinical prognostic value of miR-20a expression in GIC remains controversial.

We first conducted a comprehensive literature search of the clinical data and pooled them for evidence in assessing prognostic significance of miR-20a expression in GIC. Afterwards, we applied some bioinformatic analysis methods to explore the biological function of miR-20a and explain why miR-20a could act as an effective biomarker.

The pooled results showed that enhanced miR-20a expression was significantly associated with poor survival in GIC patients (HR: 1.36; 95%CI: 1.21–1.52; P < 0.001). According to the subgroup analysis, the ethnicity, cancer type, sample source, and sample size may have an impact on the predictive roles for miR-20a. The gene ontologies enriched by the predicted miR-20a targets were highly associated with some important biological processes, cell components and molecular functions. Moreover, a series of prominent pathways linked with GIC carcinogenesis were identified. Ultimately, the crucial targets and modules were identified by constructing the protein-protein interaction network of miR-20a targets, which were highly associated with the initiation and progression of GIC according to previous molecular biology experiments.

Our results indicated that high expression of miR-20a may be a credible indicator of worse prognosis in GIC. Further studies involving biological experiments and larger sample sizes should be performed to validate these findings.

• Function exploration
• Gastrointestinal cancer
• Prognosis prediction
• microRNA-20a

• VEGF
• angiogenesis
• c-MYB
• exosomes
• miR-155

Gastric cancer is one of the most common cancers in the world and a major cause of cancer-related death. This study aims to determine whether genetic variations in MIR155HG could be associated with gastric cancer risk.

A total of 506 gastric cancer patients and 500 healthy controls were enrolled in this study. Genotypes were examined with the MassARRAY platform and data management and analysis were conducted with the Typer Software. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with logistic regression adjusting for age and gender to evaluate the associations between SNPs with gastric cancer in genetic model analysis.

The “CC” genotype of rs4143370 decreased the risk of gastric cancer in genotype model (p = 0.020) and recessive model (p = 0.018). Inversely, the “CC” genotype of rs1893650 increased the risk of gastric cancer in genotype model (p = 0.023) and recessive model (p = 0.014). Stratified analysis showed that rs11911469 was associated with an increased risk of gastric cancer only among the male group in the dominant model (p = 0.039) and additive model (p = 0.030). The haplotype analysis showed a strong linkage disequilibrium among these six SNPs (rs4143370, rs77699734, rs11911469, rs1893650, rs34904192 and rs928883).

This study confirmed the relationship between SNPs of MIR155HG and the gastric cancer risk among the Chinese Han population. Our data may provide a new perspective to understand the aetiology of gastric cancer.

• Case-control study
• Gastric cancer
• MIR155HG
• Single nucleotide polymorphism

• MiRNA cluster
• diagnosis
• epigenetic therapy
• prognosis
• re-activation
• treatment

Background: A wealth of evidence has shown that microRNAs (miRNAs) can modulate specific genes, increasing our knowledge on the fine-tuning regulation of protein expression. miR-221 and miR-222 have been frequently identified as deregulated across different cancer types; however, their prognostic significance in cancer remains controversial. In view of these considerations, we performed an updated systematic review and meta-analysis of published data investigating the effects of miR-221/222 on overall survival (OS) and other secondary outcomes among cancer patients. A systematic search of PubMed, Web of Knowledge, and Cochrane Library databases was performed. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Results: Fifty studies, analyzing 6086 patients, were included in the systematic review. Twenty-five studies for miR-221 and 17 studies for miR-222 which assessed OS were included in the meta-analysis. High expression of miR-221 and miR-222 significantly predicted poor OS (HR: 1.48, 95% CI: 1.14–1.93, p = 0.003 and HR: 1.90, 95% CI: 1.43–2.54, p < 0.001, respectively). Subgroup analysis revealed that the finding on miR-221 was not as robust as the one on miR-222. Furthermore, high miR-222 expression was also associated with worse progression-free survival and disease-free survival pooled with recurrence-free survival. Conclusions: The meta-analysis demonstrated that high expression of miR-222 is associated with poor prognosis in cancer patients, whereas the significance of miR-221 remains unclear. More work is required to fully elucidate the role of miR-221 and miR-222 in cancer prognosis, particularly in view of the limitations of existing results, including the significant heterogeneity and limited number of studies for some cancers.

• cancer
• miR-221
• miR-222
• overall survival
• progression-free survival

• Non-small-cell lung cancer
• biomarker
• diagnosis
• miR-25
• prognosis

Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori (H. pylori) infection. Tumor necrosis factor (TNF)-α and its receptors (TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs (miRNAs), altering gene expression.

To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer (GC) tissues and its relationship.

Quantitative polymerase chain reaction (qPCR) by TaqMan^® assay was used to quantify the RNA transcript levels of TNF-α signaling pathway (TNF, TNFR1, TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway (miR-19a, miR-34a, miR-103a, miR-130a, miR-181c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases.

Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP, and NFKB2, besides CASP8 and miR-34a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103a and miR-130a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19a and miR-103a, which has as predicted or validated target a large number of genes in the TNF-α pathway, including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8.

Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.

• Gastric cancer
• Tumor necrosis factor-α signaling
• TNFR1
• TNFR2
• Cellular survival
• MicroRNAs

• gastric cancer
• lincRNA-p21
• radiotherapy
• β-catenin

• Gene Ontology
• diagnosis
• meta-analysis
• microRNA-93
• prognosis
• quantitative polymerase chain reaction

• MiRNA-221/222 cluster
• cancer
• meta-analysis
• prognosis

This study aimed to explore the correlation of circulating pro‐angiogenic miRNAs’ expressions with risk, clinicopathological features, and survival profiles in gastric cancer (GC). Three hundred and thirty‐three GC patients underwent radical resection and 117 health controls (HCs) were recruited for this study. Plasma samples were obtained from GC patients before the operation and from HCs after enrollment. Fourteen pro‐angiogenic miRNAs were asseassed by quantitative polymerase chain reaction (qPCR). Disease‐free survival (DFS) and overall survival (OS) of GC patients were calculated and the median follow‐up duration was 36.0 months. Seven out of 14 pro‐angiogenic miRNAs including let‐7f, miR‐17‐5p, miR‐18a, miR‐19b‐1, miR‐20a, miR‐210, and miR‐296 were observed to be elevated in GC patients compared with HCs. MiR‐18a, miR‐20a, and miR‐210 disclosed good predictive values of GC risk. Six pro‐angiogenic miRNAs including miR‐17‐5p, miR‐92a, miR‐210, miR‐20a, miR‐18a, and miR‐296 expressions were positively while 1 pro‐angiogenic miRNA (miR‐130a) was negatively correlated with tumor malignancy degree in GC patients. K‐M curve disclosed that 5 pro‐angiogenic miRNAs including miR‐17‐5p, miR‐18a, miR‐20a, miR‐92a, and miR‐210 correlated with worse DFS, while 4 pro‐angiogenic miRNAs including miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 associated with shorter OS. Further multivariate Cox's analysis revealed that miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 were independent predictive factors for unfavorable DFS and OS. In conclusion, circulating pro‐angiogenic miRNAs could serve as novel noninvasive biomarkers for disease risk and malignancy degree, and miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 are independent factors predicting poor prognosis in GC patients.

• circulating
• gastric cancer
• miRNA
• pro-angiogenic
• prognosis

• HOTAIR
• doxorubicin
• gastric cancer
• miR-217
• paclitaxel

• ATF7
• gastric cancer
• miRNA-103a-3p
• proliferation

• 3' Untranslated Regions
• Activating Transcription Factors/antagonists & inhibitors
• Activating Transcription Factors/genetics
• Adult
• Aged
• Aged, 80 and over
• Cell Cycle/genetics
• Cell Division
• Cell Line, Tumor
• Cohort Studies
• Databases, Factual
• Female
• Gain of Function Mutation
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• HEK293 Cells
• Humans
• Loss of Function Mutation
• Male
• MicroRNAs/genetics
• MicroRNAs/physiology
• Middle Aged
• Neoplasm Proteins/antagonists & inhibitors
• Neoplasm Proteins/genetics
• Neoplasm Proteins/physiology
• RNA/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Transcription, Genetic
• Transfection

• SERCA2a
• TRAIL
• cardiovascular diseases
• oncology
• p57

• gastric cancer
• meta-analysis
• microRNA
• prognosis

• canine
• metastasis
• microRNA
• prognostic marker
• uveal melanoma

MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren’s classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Krüppel-like Factor-4 (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4 downregulation could rescue miR-103’s oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients.

• KLF4
• gastric cancer
• metastasis
• microRNA-103
• proliferation

• MiRNA
• gastric cancer
• prognosis

• Adult
• Aged
• Biomarkers, Tumor
• Chemotherapy, Adjuvant
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Male
• MicroRNAs/genetics
• Middle Aged
• Neoplasm Grading
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/mortality

• glioma
• microRNA-548c-3p
• migration
• proliferation
• proto-oncogene c-Myb

The present study aimed to evaluate the correlation between the expression of microRNA-146a (miR-146a) and its target gene, LIN52, in advanced gastric cancer, and determine their potential effects on chemotherapeutic sensitivity and prognosis. Total RNA was extracted from 93 tissue samples of advanced gastric cancer and corresponding adjacent non-tumor tissues to quantify the relative expression levels of miR-146a using reverse transcription-quantitative polymerase chain reaction analysis. The expression of LIN52 was detected in tumors and normal tissues using immunohistochemical analysis. Correlation analysis was performed to assess the correlation between the expression of miR-146a and LIN52 and clinicopathological parameters of gastric cancer, including clinical diagnostic specificity, clinical tumor-necrosis-metastasis staging, lymph node metastasis, differentiation grade, chemotherapeutic sensitivity and prognosis. The expression of miR-146a in advanced gastric cancer tissues was lower, compared with that in the adjacent non-tumor tissues, and was negatively correlated with lymph node metastasis (P<0.05). Gastric cancer tissues with a low expression level of miR146a exhibited an increased expression level of LIN52 (P<0.05). Receiver operating characteristic curve regression analysis showed that miR-146a had 98% sensitivity in distinguishing gastric cancer tissues and adjacent non-tumor tissues. A high expression of miR-146a in gastric cancer was associated with improved treatment efficacy in patients. The chemotherapeutic sensitivity of patients with tumors expressing high levels of miR-146a was significantly higher, compared with that of patients with tumors expressing low levels of miR-146a (P<0.05). The expression of miR-146a was low in advanced gastric cancer tissues. As a tumor suppressor gene in advanced gastric cancer, miR-146a had a significant negative correlation with LIN52. High expression levels of miR-146a in advanced gastric cancer tissue may be associated with improved treatment efficacy of chemotherapy, suggesting that miR-146a may be a molecular marker for the diagnosis, prediction of treatment efficacy and prognosis of advanced gastric cancer.

• LIN52
• advanced gastric cancer
• chemotherapeutic sensitivity
• diagnosis
• lymph node metastasis
• microRNA-146a

MicroRNA (miRNA)-25 is a small non-coding RNA that has been implicated in the tumorigenesis of many cancers, but little is known on the role of miR-25 in HCC metastasis. We hereby found that miR-25 was significantly upregulated in clinical HCC tissues compared with normal liver tissues. We also revealed that miR-25 dramatically stimulates HCC cell growth and activates the epithelial-mesenchymal transition (EMT). MiR-25 is activated by the WNT/β-catenin signaling pathway, and exerts its pro-metastatic function by directly inhibiting the Rho GDP dissociation inhibitor alpha (RhoGDI1). Downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. MiR-25 levels are positively correlated with β-catenin expression, whereas negatively correlated with the level of RhoGDI1 in HCC. Our findings provide new insights into the role of miR-25 in HCC metastasis, and implicate the potential application of miR-25 in HCC therapy.

• RhoGDI1
• hepatocellular carcinoma
• metastasis
• miR-25

• Biomarker
• Cancer
• MiR-106a
• MicroRNA
• Oncogene

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity.

• Gastric cancer
• Epigenetic
• Diagnostic biomarkers
• miRNAs
• Prognostic biomarkers

• Biomarkers, Tumor/metabolism
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/metabolism
• MicroRNAs/therapeutic use
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Prognosis
• RNA, Messenger/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

Genetic and epigenetic alterations play an important role in gastric cancer (GC) pathogenesis. Aberrations of the phosphatidylinositol-3-kinase signaling pathway are well described. However, emerging genes have been described such as, the chromatin remodeling gene ARID1A. Our aim was to determine the expression levels of four GC-related genes, ARID1A, CDH1, cMET and PIK3CA, and 14 target-related microRNAs (miRNAs).

We compared mRNA and miRNA expression levels among 66 gastric tumor and normal adjacent mucosa samples using quantitative real-time reverse transcription PCR. Moreover, ARID1A, cMET and PIK3CA protein levels were assessed by immunohistochemistry (IHC). Finally, gene and miRNAs associations with clinical characteristics and outcome were also evaluated.

An increased cMET and PIK3CA mRNA expression was found in 78.0% (P = 2.20 × 10⁻⁵) and 73.8% (P = 1.00 × 10⁻³) of the tumors, respectively. Moreover, IHC revealed that cMET and PIK3CA expression was positive in 63.6% and 87.8% of the tumors, respectively. Six miRNAs had significantly different expression between paired-samples, finding five up-regulated [miR-223-3p (P = 1.65 × 10⁻⁶), miR-19a-3p (P = 1.23 × 10⁻⁴), miR-128-3p (P = 3.49 × 10⁻⁴), miR-130b-3p (P = 1.00 × 10⁻³) and miR-34a-5p (P = 4.00 × 10⁻³)] and one down-regulated [miR-124-3p (P = 0.03)].

Our data suggest that cMET, PIK3CA and target-related miRNAs play an important role in GC and may serve as potential targets for therapy.

• biomarkers
• gastric cancer
• gene expression
• immunohistochemistry
• microRNA expression

Gastric cancer (GC) is one of the leading causes of cancer-related deaths throughout China and worldwide. The discovery of microRNAs (miRNAs) has provided a new opportunity for developing diagnostic biomarkers and effective therapeutic targets in GC. By performing microarray analyses of benign and malignant gastric epithelial cell lines (HFE145, NCI-N87, MKN28, RF1, KATO III and RF48), 16 significantly dysregulated miRNAs were found. 11 of these were validated by real-time qRT-PCR. Based on miRWalk online database scans, 703 potential mRNA targets of the 16 miRNAs were identified. Bioinformatic analyses suggested that these dysregulated miRNAs and their predicted targets were principally involved in tumor pathogenesis, MAPK signaling, and apoptosis. Finally, miRNA-gene network analyses identified miRNA-125b as a crucial miRNA in GC development. Taken together, these results develop a comprehensive expression and functional profile of differentially expressed miRNAs related to gastric oncogenesis. This profile may serve as a potential tool for biomarker and therapeutic target identification in GC patients.

• bioinformatics
• gastric cancer
• miRNA profiling

The prognosis of non-small-cell lung cancer (NSCLC) is poor yet mechanistic understanding and therapeutic options remain limited. We investigated the biological and clinical significance of microRNA-130b and its relationship with apoptosis in NSCLC.

The level of microRNA-130b in relationship with the expression of PPARγ, VEGF-A, BCL-2 and apoptosis were analyzed in 91 lung cancer patient samples using immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on tissue microarrays. Gain and loss-of-function studies were performed to investigate the effects of microRNA-130b, peroxisome proliferator-activated receptor γ (PPARγ) or vascular endothelial growth factor-A (VEGF-A) on biological functions of lung cancer cells using in vitro and in vivo approaches.

MicroRNA-130b up-regulation conferred unfavorable prognosis of lung cancer patients. Notably, microRNA-130b targeted PPARγ and inhibiting microRNA-130b markedly repressed proliferation, invasion and metastasis of lung cancer cells, leading to increased apoptosis. MicroRNA-130b-dependent biologic effects were due to suppression of PPARγ that in turn activated BCL-2, the key mediator of anti-apoptosis. Administration of microRNA-130b mimic to mouse xenografts promoted tumor growth. In vitro and in vivo, miR-130b enrichment associated with down-regulation of PPARγ, up-regulation of VEGF-A and BCL-2, and decreased apoptosis.

The present study demonstrates that microRNA-130b promotes lung cancer progression via PPARγ/VEGF-A/BCL-2-mediated suppression of apoptosis. Targeting microRNA-130b might have remarkable therapeutic potential for lung cancer therapy.

The online version of this article (doi:10.1186/s13046-016-0382-3) contains supplementary material, which is available to authorized users.

• Apoptosis
• BCL-2
• MicroRNA-130b
• NSCLC
• PPARγ

• Apoptosis
• Cell cycle
• Cyclin D1
• Gastric cancer
• MicroRNA-155
• Proliferation

• Apoptosis
• Cell Cycle/genetics
• Cell Line, Tumor
• Cell Proliferation/genetics
• Cyclin D1/genetics
• Down-Regulation
• Humans
• MicroRNAs/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology

• gastric adenocarcinoma
• microrna expression profile
• epstein-barr virus
• formalin fixed tissue
• plasma
• biomarker
• honduras

• Adenocarcinoma/genetics
• Adenocarcinoma/metabolism
• Adenocarcinoma/virology
• Aged
• Aged, 80 and over
• Case-Control Studies
• Epstein-Barr Virus Infections/genetics
• Epstein-Barr Virus Infections/metabolism
• Epstein-Barr Virus Infections/virology
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Herpesvirus 4, Human/genetics
• Herpesvirus 4, Human/isolation & purification
• Humans
• Male
• MicroRNAs/blood
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Pilot Projects
• RNA, Neoplasm/blood
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• RNA, Viral/blood
• RNA, Viral/genetics
• RNA, Viral/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/virology

• U10 CA181009 NCI NIH HHS
• KL2 TR001109 NCATS NIH HHS
• P30 CA016086 NCI NIH HHS
• HHSN261200800001C NCI NIH HHS
• P30 CA068485 NCI NIH HHS
• HHSN261200800001E NCI NIH HHS
• K07 CA125588 NCI NIH HHS
• R21 CA155543 NCI NIH HHS