• Biomarkers
• Diagnosis
• Gastric cancer
• Predicting treatment response
• Prognosis

• Stomach Neoplasms/diagnosis
• Humans
• Biomarkers, Tumor/urine
• Prognosis

• PD-L1
• gastric cancer
• immunotherapy
• lactylation-related genes
• prognostic signature

• Cancer
• EGF
• Pathogenesis
• Signaling
• miRNA

• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Signal Transduction/genetics
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/pathology
• Epidermal Growth Factor/metabolism
• Epidermal Growth Factor/genetics
• Animals
• Gene Expression Regulation, Neoplastic
• ErbB Receptors/metabolism
• ErbB Receptors/genetics

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Bayes Theorem
• Humans
• Computational Biology/methods
• Algorithms
• Genetic Predisposition to Disease/genetics
• Logistic Models

• The Ministry of Education of China project of Humanities and Social Sciences
• Natural Science Foundation of Fujian Province

• DNA repair
• cancer
• epigenetic
• inflammation
• nutrition

• Apoptosis
• Cancer
• Chemoresistance
• Exosome
• MicroRNA-146a

• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Apoptosis/genetics
• Neoplasms/genetics
• Biomarkers

• RTK-RNAs
• Receptor tyrosine kinase
• Solid tumors
• circRNA
• lncRNA
• miRNA

• cancer
• genetic variation
• germline
• mutation
• noncoding RNAs
• somatic mutation

• Humans
• Gene Regulatory Networks
• Mutation
• MicroRNAs/genetics
• Neoplasms/genetics
• RNA, Untranslated/genetics
• RNA, Long Noncoding/genetics
• Genetic Predisposition to Disease

• Humans
• Prognosis
• Memory B Cells
• MicroRNAs/genetics
• Adenocarcinoma/genetics
• Algorithms
• Tumor Microenvironment/genetics

• The Grant of 2021 Foreign Experts of the Department of Science and Technology of Guangdong Province

• Molecular diagnostics
• Non-coding RNA
• TNBC
• miRNA
• microRNA-146a

• cancer
• canine
• expression
• mammary gland
• microRNA
• tumor

• Carcinogenesis/genetics
• Cell Transformation, Neoplastic/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/therapy

MicroRNAs are a class of small non-coding RNA molecules that regulate gene expression on post-transcriptional level. Their biogenesis consists of a complex series of sequential processes, and they regulate expression of many genes involved in all cellular processes. Their function is essential for maintaining the homeostasis of a single cell; therefore, their aberrant expression contributes to development and progression of many diseases, especially malignant tumors and viral infections. Moreover, they can be associated with certain states of a specific disease, obtained in the least invasive manner for patients and analyzed with basic molecular methods used in clinical laboratories. Because of this, they have a promising potential to become very useful biomarkers and potential tools in personalized medicine approaches. In this review, miRNAs biogenesis, significance in cancer and infectious diseases, and current available test and methods for their detection are summarized.

• DR
• VEGF
• inflammation
• miR-146a
• patient

• Cytokines/genetics
• Cytokines/metabolism
• Diabetes Mellitus, Type 2/genetics
• Diabetic Retinopathy/genetics
• Humans
• Inflammation/genetics
• MicroRNAs/genetics
• NF-kappa B/metabolism
• Vascular Endothelial Growth Factor A/genetics

• carbohydrate antigen 72-4
• diagnostic value
• gastric cancer
• miR-181
• miR-652

• Antigens, Tumor-Associated, Carbohydrate/biosynthesis
• Antigens, Tumor-Associated, Carbohydrate/blood
• Antigens, Tumor-Associated, Carbohydrate/genetics
• Biomarkers, Tumor/biosynthesis
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Early Detection of Cancer/methods
• Humans
• MicroRNAs/biosynthesis
• MicroRNAs/blood
• MicroRNAs/genetics
• Prognosis
• ROC Curve
• Stomach Neoplasms/blood
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

Although long non-coding RNAs (lncRNAs) have been demonstrated to be dysregulated in gastric cancer (GC), the function of lncRNA HCG18 (HCG18) in GC is elusive. Therefore, the study was designed to evaluate the underlying mechanism of HCG18 in GC. HCG18 and microRNA 146a-5p (miR-146a-5p) levels in GC were evaluated by RT-qPCR. The effects of miR-146a-5p and HCG18 on GC cell function were examined using Transwell assay, colony formation, and CCK-8 assays. Tumor necrosis factor receptor-associated factor 6 (TRAF6) and p65 expression levels were detected by Western blot. HCG18 and miR-146a-5p target genes were identified using luciferase reporter and bioinformatics assays. HCG18 expression was increased in GC. HCG18 overexpression significantly increased GC cell proliferation, invasion, and migration. Furthermore, HCG18 overexpression inhibited miR-146a-5p and upregulated TRAF6 and p65 expression. Finally, miR-146a-5p/TRAF6 was found to be involved in the role of HCG18 in GC progression in vivo. Altogether, HCG18 promotes GC progression via the miR-146a-5p/TRAF6 axis and could be a GC treatment target.

• HCG18
• TRAF6
• gastric cancer
• miR-146a-5p
• p65
• proliferation

Histone deacetylases (HDACs) have been identified to be implicated in the carcinogenesis and cancer progression. The present study was performed to probe into the effect of HDAC4 on radioresistance of esophageal carcinoma (EC).

The expression of HDAC4 in responders and non-responders to radiotherapy was characterized by RT-qPCR, immunohistochemistry, and Western blot analysis. EC cells were exposed to continuous fractionated X-ray irradiation, and their proliferation and apoptosis were evaluated by means of colony formation assay and flow cytometry based Annexin V-FITC/PI apoptosis assay in response to HDAC4 overexpression or silencing. Mechanistic investigation was conducted by means of in silico analysis and dual-luciferase reporter gene assay. Tumor xenografts derived from radioresistant EC cells were exposed to local X-ray irradiation in vivo for validation.

High expression of HDAC4 was detected in either tumor tissues derived from radiotherapy responders or radioresistant EC cells. Loss of HDAC4 contributed to suppressed proliferation and enhanced apoptosis of radioresistant EC cells. Moreover, our findings revealed that HDAC4 conferred radioresistance of EC by downregulating microRNA-146a (miR-146a). Interleukin-1 receptor-associated kinase 1 (IRAK1) was a target of miR-146a, and its knockdown promoted radiosensitivity. Silencing of HDAC4 radiosensitized EC cells both in vitro and in vivo via the miR-146a/IRAK1 axis.

Hence, loss of HDAC4 upregulated miR-146a to limit radioresistance. This study aids in the better understanding about mechanism responsible for radioresistance of EC.

The online version contains supplementary material available at 10.1186/s12967-021-03171-z.

• Esophageal carcinoma
• Histone deacetylase 4
• IRAK1
• In vitro and in vivo studies
• Radioresistance
• miR-146a

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

• nano silver
• silver nitrate
• transcriptomics
• microrna expression
• target filter analysis
• signaling pathways

• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/genetics
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/genetics
• Metal Nanoparticles/toxicity
• MicroRNAs/genetics
• RNA, Messenger/genetics
• Silver/toxicity
• Silver Nitrate/toxicity

• EPA999999 Intramural EPA

Gastric cancer (GC), a common malignancy of the human digestive system, represents the second leading cause of cancer-related deaths worldwide. Early detection of GC has a significant impact on clinical outcomes. The aim of this study was to identify potential GC biomarkers.

In this study, we conducted a multi-step analysis of expression profiles in GC clinical samples downloaded from TCGA database to identify differentially expressed miRNAs (DEMs) and differentially expressed mRNAs (DEGs). Potential prognostic biomarkers from the available DEMs were then established using the Cox regression method. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological role of the predicted target genes of the miRNA biomarkers. Then, the prognostic DEM-mediated regulatory network was constructed based on transcription factor (TF)–miRNA–target interaction. Subsequently, the consensus genes were further determined based on the overlap between DEGs and these target genes of DEMs. Besides, expression profile, co-expression analysis, immunity, and prognostic values of these prognostic genes were also investigated to further explore the roles in the mechanism of GC tumorigenesis.

We got five miRNAs, including miR-23b, miR-100, miR-143, miR-145, and miR-409, which are associated with the overall survival of GC patients. Subsequently, enrichment analysis of the target genes of the miRNA biomarkers shown that the GO biological process terms were mainly enriched in mRNA catabolic process, nuclear chromatin, and RNA binding. In addition, the KEGG pathways were significantly enriched in fatty acid metabolism, extracellular matrix (ECM) receptor interaction, and proteoglycans in cancer pathways. The transcriptional regulatory network consisting of 68 TFs, 4 DEMs, and 58 targets was constructed based on the interaction of TFs, miRNAs, and targets. The downstream gene ETS1 of miR-23b and TCF4 regulated by ETS1 were obtained by the regulatory network construction and co-expression analysis. High expression of ETS1 and TCF4 indicated poor prognosis in GC patients, particularly in the advanced stages. The expression of ETS1 and TCF4 was correlated with CD4⁺ T cells, CD8⁺ T cells, and B cells.

miR-23b, ETS1, and TCF4 were identified as the prognostic biomarkers. ETS1 and TCF4 had potential immune function in GC, which provided a theoretical basis for molecular-targeted combined immunotherapy in the future.

• Bioinformatics analysis
• Differentially expressed genes
• Gastric carcinoma
• Immunity
• Transcription factors
• miRNAs

Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes including essential cellular functions. miR146-a acts as an inhibitor of interleukin 1 receptor associated kinase 1 (IRAK1) and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6) present in the toll-like receptors pathway while miR499a modulates TGF-β and TNF signalling pathways. Here, we investigated whether MIRNA146A rs2910164 and MIRNA499 rs3746444 variants are associated with the development of L. guyanensis (Lg)-cutaneous leishmaniasis (CL). The variants MIR146A rs2910164 and MIR499A rs3746444 were assessed in 850 patients with Lg-CL and 891 healthy controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma cytokines were measured using the BioPlex assay. Carriers of rs2910164 CC genotype have 30% higher odds of developing CL (ORadj_age/sex = 1.3 [95%CI 0.9–1.8]; Padj_age/sex 0.14) compared to individuals with the genotype GG (ORadj_age/sex = 0.77 [95%CI 0.56–1.0]; Padj_age/sex 0.14) if exposed to Lg-infection. Heterozygous GC individuals also showed lower odds of developing CL (ORadj_age/sex = 0.77 [95%CI 0.5–1.1]; Padj_age/sex 0.09). Homozygosity for the allele C is suggestive of an association with the development of Lg-CL among exposed individuals to Lg-infection. However, the odds of developing CL associated with the CC genotype was evident only in male individuals (OR_adjage = 1.3 [95% CI = 0.9–2.0]; P_adjage = 0.06). Individuals homozygous for the G allele tend to have higher plasma IL-8 and CCL5. Similarly, for the MIR499A rs3746444, an association with the G allele was only observed among male individuals (OR = 1.4 [1.0–1.9]; P = 0.009). In a dominant model, individuals with the G allele (GG-GA) when compared to the AA genotype reveals that carriers of the G allele have 40% elevated odds of developing Lg-CL (ORadj_age = 1.4 [1.1–1.9]). Individuals with the GG genotype have higher odds of developing Lg-CL (ORadj_age/sex = 2.0 [95%CI 0.83–5.0]; P_adjage = 0.01. Individuals homozygous for the G allele have higher plasma IL-8. Genetic combinations of both variants revealed that male individuals exposed to Lg bearing three or four susceptible alleles have higher odds of developing Lg-CL (OR = 2.3 [95% CI 1.0–4.7]; p = 0.017). Both MIR146A rs2910164 and MIR499A rs3746444 are associated with the development of Lg-CL and this association is prevalent in male individuals.

Leishmaniasis is caused by infection with Leishmania parasites. In regions with the presence of Leishmania parasites, all people do not develop the disease despite similar exposure. Only a proportion of inhabitants progress to the development of disease. Clinical manifestations depend on the vector and Leishmania species, as well the host genetic background and genetically determined immune responses. miRNAs play important roles in regulating gene expression and many biological processes including immune pathways. miR-146a targets TRAF6 and IRAK1 genes, that encode key adaptor molecules downstream of toll-like receptors (TLRs). TLRs are critical in immune response to Leishmania-infection. miR499-a modulates inflammation-related signalling pathways such as TGFβ, TNFα and TLR pathways. In this study, we showed that MIR146A and MIR499A variants are risk factors to developing cutaneous leishmaniasis caused by L. guyanensis in Amazonas state of Brazil. Individuals with these variants are susceptible to the development of CL.

• Adult
• Alleles
• Cytokines/blood
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interleukin-1 Receptor-Associated Kinases
• Interleukin-8/blood
• Interleukin-8/metabolism
• Intracellular Signaling Peptides and Proteins
• Leishmania guyanensis
• Leishmaniasis, Cutaneous/genetics
• Male
• MicroRNAs/genetics
• Middle Aged
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide

• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Fundação de Amparo à Pesquisa do Estado do Amazonas

Epidemiological and experimental evidence indicate that selenium is associated with a reduced risk of some cancers, including esophageal cancer. However, the exact mechanism is still unclear. In the present study, we used esophageal squamous cell carcinoma (ESCC) cell lines and animal models to explore the anti-cancer mechanism of methylseleninic acid (MSA). Firstly, MSA treatment dramatically attenuated Epidermal Growth Factor Receptor (EGFR) protein expression but did not alter mRNA levels in ESCC cells. On the contrary, EGFR overexpression partly abolished the inhibitory effect of MSA. With a microRNA-array, we found MSA up-regulated miR-146a which directly targeted EGFR, whereas miR-146a inhibitor antagonized MSA-induced decrease of EGFR protein. We further used 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumor mice model to evaluate the inhibitory effect of MSA in vivo. MSA treatment significantly decreased the tumor burden and EGFR protein expression in tumor specimens. Furthermore, MSA treatment inhibited EGFR pathway and subsequntly reduced Interleukin-6 (IL-6) secretion in the supernatant of cancer cell lines. MSA-induced IL-6 suppression was EGFR-dependent. To further evaluate the association of IL-6 and the anti-tumor effect of MSA on esophageal cancer, we established the 4NQO-induced esophageal tumor model in IL-6 knock-out (IL-6 KO) mice. The results showed that IL-6 deficiency did not affect esophageal tumorigenesis in mice, but the inhibitory effect of MSA was abolished in IL-6 KO mice. In conclusion, our study demonstrated that MSA upregulated miR-146a which directly targeted EGFR, and inhibited EGFR protein expression and pathway activity, subsequently decreased IL-6 secretion. The inhibitory effect of MSA on esophageal cancer was IL-6 dependent. These results suggested that MSA may serve as a potential drug treating esophageal cancer.

• EGFR
• ESCC
• IL-6
• MSA
• miR-146a

• Gastric cancer
• Gastric carcinogenesis
• Gastric preneoplastic conditions
• microRNAs

• ADAM
• CAM assay
• L1
• RB
• chemoresistance
• etoposide

• Gene expression
• glioblastoma
• in vitro cell culture
• miRNA-mRNA-pathway interactions
• microRNA
• propolis

• Cisplatin
• Esophagogastric cancer
• Gemcitabine
• MicroRNA
• Vitamin B12

• Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Cisplatin/administration & dosage
• Clinical Trials, Phase II as Topic
• Deoxycytidine/administration & dosage
• Deoxycytidine/analogs & derivatives
• Esophageal Neoplasms/blood
• Esophageal Neoplasms/drug therapy
• Esophagogastric Junction
• Female
• Folic Acid/administration & dosage
• Humans
• Male
• MicroRNAs/blood
• Middle Aged
• Palliative Care
• Prognosis
• Progression-Free Survival
• Randomized Controlled Trials as Topic
• Stomach Neoplasms/blood
• Stomach Neoplasms/drug therapy
• Survival Rate
• Gemcitabine

• miR-30b-5p
• miRNAs
• prognostic biomarkers
• renal cell carcinoma

• Aged
• Biomarkers, Tumor/genetics
• Carcinoma, Renal Cell/genetics
• Carcinoma, Renal Cell/mortality
• Carcinoma, Renal Cell/pathology
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Kidney Neoplasms/genetics
• Kidney Neoplasms/mortality
• Kidney Neoplasms/pathology
• Male
• MicroRNAs/genetics
• Middle Aged
• Prognosis
• ROC Curve
• Up-Regulation

Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated.

Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting.

The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p.

These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

• Gastric cancer
• MAPK10
• Proliferation
• miR-335-5p

• DGCR8
• DROSHA
• miR-146a
• miRNA
• rs2910164
• single nucleotide polymorphism

• Disease/genetics
• Humans
• MicroRNAs/chemistry
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Polymorphism, Single Nucleotide
• RNA Processing, Post-Transcriptional
• Ribonuclease III/chemistry
• Ribonuclease III/metabolism

• National Natural Science Foundation of China

• chemoresistance
• gastric cancer
• markers
• metastasis
• microRNA
• signaling pathways

• 01201363640 Ministry of Science and Higher Education of the Russian Federation

Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM.

In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis.

We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13–0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14–0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28–0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050).

Our findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.

• asbestos
• genetic variation
• malignant mesothelioma
• miRNA
• pleural plaques

• MicroRNA-7
• Raf-1
• apoptosis
• gastric cancer
• invasion
• migration
• neoadjuvant chemotherapy
• proliferation

• Adult
• Aged
• Animals
• Apoptosis
• Case-Control Studies
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Chemotherapy, Adjuvant
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Microvascular Density
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Invasiveness
• Neovascularization, Pathologic
• Proto-Oncogene Proteins c-raf/genetics
• Proto-Oncogene Proteins c-raf/metabolism
• Signal Transduction
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/enzymology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology

• Stomach cancer
• circRNA
• lncRNA
• miRNA
• piRNA

• BRCA1/2
• Colorectal cancer
• SNV n.60G>C (rs2910164)
• miR-146a
• prognosis
• risk
• single-nucleotide variant

• gastric cancer
• metastasis
• miR-146a
• miR-335
• miR-34a

• Breast cancer-derived exosome
• CAFs
• Invasion and metastasis
• TXNIP
• Wnt pathway
• miR-146a

• human umbilical vein endothelial cells
• invasion
• microRNA-144
• migration
• rapamycin-insensitive companion of mTOR

• Apoptosis
• Gastric cancer
• PTP1B
• Proliferation
• miR-146b

It is widely known that some specific microRNAs can regulate the expressions of genes in gastric cancer cells at the post-transcriptional level. Previous studies have identified that miRNA-4766-5p was involved in tumor cell proliferation and can be an independent prognostic indicator for malignant pleural mesothelioma. However, the mechanism underlying gastric cancer via the miRNA-4766-5p pathway remains to be blank.

We investigated the expression of miR-4766-5p in gastric cancer tissues and cells through qRT-PCR. We used RNAi to change the expressions of miR-4766-5p in gastric cancer cell lines, AGS and MKN45. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the mRNA expression of miR-4766-5p. We identified cell proliferation by CCK8 and clone formation assays. We analyzed the cell apoptosis and cycle through flow cytometry. At last, we used a dual-luciferase reporter assay to illustrate the interaction between miR-4766-5p and NKAP and used Western blot to determine the protein expression of signaling pathways.

We found that 1) miR-4766-5p was down-regulated in gastric cancer tissues and cells lines; 2) miR-4766-5p inhibited cell proliferation of gastric cancer cell lines significantly; 3) miR-4766-5p significantly inhibited cell migration and invasion of gastric cancer cells; 4) miR-4766-5p induced gastric cancer cell apoptosis. 5) NKAP was a direct target gene of miR-4766-5p; and 6) miR-4766-5p induced inactivation of AKT/mTOR pathway.

The above results indicate that miR-4766-5p suppressed the proliferation and metastasis of gastric cancer cells through targeting NKAP. Our findings could probably contribute to the diagnostics and prognostics of gastric cancer through new methodologies.

• NKAP
• gastric cancer
• miR-4766-5p
• progression

The incidence of cancer and Alzheimer’s disease (AD) increases exponentially with age. A growing body of epidemiological evidence and molecular investigations inspired the hypothesis of an inverse relationship between these two pathologies. It has been proposed that the two diseases might utilize the same proteins and pathways that are, however, modulated differently and sometimes in opposite directions. Investigation of the common processes underlying these diseases may enhance the understanding of their pathogenesis and may also guide novel therapeutic strategies. Starting from a text-mining approach, our in silico study integrated the dispersed biological evidence by combining data mining, gene set enrichment, and protein-protein interaction (PPI) analyses while searching for common biological hallmarks linked to AD and cancer. We retrieved 138 genes (ALZCAN gene set), computed a significant number of enriched gene ontology clusters, and identified four PPI modules. The investigation confirmed the relevance of autophagy, ubiquitin proteasome system, and cell death as common biological hallmarks shared by cancer and AD. Then, from a closer investigation of the PPI modules and of the miRNAs enrichment data, several genes (SQSTM1, UCHL1, STUB1, BECN1, CDKN2A, TP53, EGFR, GSK3B, and HSPA9) and miRNAs (miR-146a-5p, MiR-34a-5p, miR-21-5p, miR-9-5p, and miR-16-5p) emerged as promising candidates. The integrative approach uncovered novel miRNA-gene networks (e.g., miR-146 and miR-34 regulating p62 and Beclin1 in autophagy) that might give new insights into the complex regulatory mechanisms of gene expression in AD and cancer.

• Alzheimer
• cancer
• data mining
• enrichment analysis
• genes
• inverse relationship
• miRNAs
• protein-protein interaction network

MicroRNAs (miRNAs/miRs), consisting of ~22 nucleotides of single-stranded RNA, participate in post-transcriptional gene regulation by binding to the 3′-untranslated region (UTR) of mRNAs, repressing their translation and promoting their degradation. Studies have shown that certain miRNAs play a key role in the control of various cellular activities, such as inhibiting inflammation, modulating cell differentiation and suppressing cancer growth. The role of miR-146a in the immune response and in the pathogenesis of hepatocellular carcinoma (HCC) has also been investigated. Although some studies have shown that increased miR-146a levels are associated with HCC, others have revealed that miR-146a suppresses cancer cell proliferation, invasion and metastasis. Toll-like receptor 4 (TLR4) signaling has an important role in regulating innate and adaptive immune responses. In addition, TLR4 is functionally expressed in HCC cells and promotes HCC cell proliferation, which can be regulated by miR-146a. The present review focuses on the recent progress in analyzing the multiple roles of miR-146a in mediating the TLR4 pathway and adaptive immune response. Finally, the function of miR-146a in the pathogenesis of HCC is also discussed.

• Toll-like receptor 4
• gene polymorphism
• hepatocellular carcinoma
• immune response
• microRNA-146a
• target