• coagulation
• inflammation
• signal transduction
• thrombin
• thrombomodulin

• Humans
• Thrombomodulin/metabolism
• Thrombin/metabolism
• Protein C/metabolism
• Endothelial Cells/metabolism
• Tensins
• Anticoagulants
• Phosphoric Monoester Hydrolases

• R01 HL101917 NHLBI NIH HHS

• CASP3
• PIK3CA
• Tiao-Yuan-Tong-Wei decoction
• agrimoniin
• baicalin
• corosolic acid
• gastric cancer

• 713654 H2020 Marie Skłodowska-Curie Actions

• Chronic atrophic gastritis
• Inflammation-cancer transformation
• JianPi QingRe HuaYu Methods
• Quercetin

• Humans
• Stomach Neoplasms/drug therapy
• Network Pharmacology
• Molecular Docking Simulation
• Quercetin
• Gastritis/drug therapy
• Inflammation/drug therapy
• Cytokines
• Drugs, Chinese Herbal

• 2022JJ40706 Natural Science Foundation of Hunan Province

• Biomarkers
• Gastric cancer
• MiR-619-5p
• Prognosis
• Target genes

• Humans
• MicroRNAs/genetics
• Prognosis
• Stomach Neoplasms/genetics
• Reproducibility of Results
• Computational Biology
• Biomarkers
• Gene Expression Regulation, Neoplastic
• Adaptor Proteins, Signal Transducing/genetics
• Chromosomal Proteins, Non-Histone

• 20ZD7FA003 Major Scientific and Technological Special Project of Guizhou Province
• 21JR1RA122 Science and Technology Program of Gansu Province

• CDK
• CDK4/6 inhibition
• cell cycle
• chemotherapy
• non-coding RNA

• PRMT5
• Wnt/β-Catenin signaling
• gastric epithelium
• tumorigenesis

The clinical aspects of hypertrophic scarring vary according to personal constitution and body part. However, the mechanism of hypertrophic scar (HS) formation remains unclear. MicroRNAs (miRNAs) are known to contribute to HS formation, however, their detailed role remains unknown. In this study, candidate miRNAs were identified and analyzed as biomarkers of hypertrophic scarring for future clinical applications. HSfibroblasts and normal skin fibroblasts from patients were used for profiling and validation of miRNAs. An HS mouse model with xenografted human skin on nude mice was established. The miRNA expression between normal human, normal mouse, and mouse HS skin tissues was compared. Circulating miRNA expression levels in the serum of normal mice and mice with HSs were also analyzed. Ten upregulated and twenty-one downregulated miRNAs were detected. Among these, miR-365a/b-3p and miR-16-5p were identified as candidate miRNAs with statistically significant differences; miR-365a/b-3p was significantly upregulated (p = 0.0244). In mouse studies, miR-365a/b-3p expression levels in skin tissue and serum were higher in mice with HSs than in the control group. These results indicate that miRNAs contribute to hypertrophic scarring and that miR-365a/b-3p may be considered a potential biomarker for HS formation.

• hypertrophic scar
• microRNA
• myofibroblast

• Animals
• Biomarkers/metabolism
• Cicatrix, Hypertrophic/genetics
• Circulating MicroRNA
• Gene Expression Profiling
• Humans
• Mice
• Mice, Nude
• MicroRNAs/metabolism

• IDH1 mutation
• ceRNA regulatory network
• glioma
• mechanisms’ exploration
• muti-omics immune-related bioinformatics research
• prognostic model
• tumor immunosuppressive environment

Doxorubicin (DOX) has limited chemotherapy application for malignancies due to cardiotoxicity. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is yet to be elucidated. Increasing studies proved that activation of AKT prevented cardiomyocyte apoptosis and cardiac dysfunction in response to DOX insult. Our previous studies indicated that major vault protein (MVP) deficiency was accompanied by suppressed phosphorylation of AKT in metabolic diseases. This study aimed to investigate the role and underlying mechanism of MVP on cardiomyocyte apoptosis in DiCM.

Mice were intraperitoneally injected with DOX 5 mg/kg, once a week for 5 weeks, the total cumulative dose was 25 mg/kg. Cardiomyocyte-specific MVP overexpression was achieved using an adeno-associated virus system under the cTnT promoter after the fourth DOX injection. Cardiac function was examined by echocardiography followed by euthanasia. Tissue and serum were collected for morphology analysis and biochemical examination.

Herein, we found that MVP expression was upregulated in DOX-treated murine hearts. Cardiac-specific MVP overexpression alleviated DOX-induced cardiac dysfunction, oxidative stress and fibrosis. Mechanistically, MVP overexpression activated AKT signaling and decreased cardiomyocyte apoptosis in DiCM.

Based on these findings, we supposed that MVP was a potential therapeutic agent against DiCM.

The online version contains supplementary material available at 10.1186/s12872-022-02517-9.

• AKT
• Apoptosis
• Doxorubicin-induced cardiomyopathy
• Major vault protein

• Gastric cancer cell apoptosis
• Metformin
• MiR-365
• PTEN

• 3' Untranslated Regions
• AMP-Activated Protein Kinases/metabolism
• Animals
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Metformin/pharmacology
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• PTEN Phosphohydrolase/genetics
• PTEN Phosphohydrolase/metabolism
• Phosphorylation
• Signal Transduction
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Tumor Burden/drug effects
• Xenograft Model Antitumor Assays
• Mice

• Apoptosis
• HOXA9
• Invasion
• MicroRNA
• Multiple myeloma
• Proliferation
• miR-365

• Animals
• Apoptosis/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Female
• Homeodomain Proteins/genetics
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs
• Multiple Myeloma/genetics
• Multiple Myeloma/pathology
• Mice

• complement cascade
• post-translational modifications

• Gallbladder carcinoma
• cancer stem cell
• miR-365
• prognosis
• rac1

MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts. Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically bta-miR-365-3p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.

Firstly, we found that bta-miR-365-3p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of bta-miR-365-3p significantly reduced the expression levels of cyclin D1 (CCND1), cyclin dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) but stimulated the expression levels of muscle differentiation markers, i.e., MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3p resulted in the opposite consequences. Finally, we identified that activin A receptor type I (ACVR1) could be a direct target of bta-miR-365-3p. It was demonstrated that bta-miR-365-3p can bind to the 3’UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays. Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level.

Collectively, these data suggested that bta-miR-365-3p represses proliferation but promotes differentiation of bovine myoblasts through several biological mechanisms involving downregulation of ACVR1.

The online version contains supplementary material available at 10.1186/s40104-020-00528-0.

• ACVR1
• Bta-miR-365-3p
• Cattle
• Primary bovine myoblast

Background: Pepsinogen (PG) II (PGII) is a serological marker used to estimate the risk of gastric cancer but how PGII expression is regulated is largely unknown. It has been suggested that PGII expression, from the PGC (Progastricsin) gene, is regulated by microRNAs (miRNA), but how PGII levels vary with Helicobacter pylori (H. pylori) infection and miRNAs genotype remains unclear. Methods: Serum levels of PGI and PGII were determined in 80 patients with gastric cancer and persons at risk for gastric cancer (74 first-degree relatives of patients, 62 patients with autoimmune chronic atrophic gastritis, and 2 patients with dysplasia), with and without H. pylori infection. As control from the general population, 52 blood donors were added to the analyses. Associations between PGII levels and genetic variants in PGC and miRNA genes in these groups were explored based on H. pylori seropositivity and the risk for gastric cancer. The two-dimensional difference in gel electrophoresis (2D-DIGE) and the NanoString analysis of messenger RNA (mRNAs) from gastric cancer tissue were used to determine the pathways associated with increased PGII levels. Results: PGII levels were significantly higher in patients with gastric cancer, and in those with H. pylori infection, than in other patients or controls. A PGI/PGII ratio ≤ 3 was found better than PGI < 25 ng/mL to identify patients with gastric cancer (15.0% vs. 8.8%). For two genetic variants, namely rs8111742 in miR-Let-7e and rs121224 in miR-365b, there were significant differences in PGII levels between genotype groups among patients with gastric cancer (p = 0.02 and p = 0.01, respectively), but not among other study subjects. Moreover, a strict relation between rs9471643 C-allele with H. pylori infection and gastric cancer was underlined. Fold change in gene expression of mRNA isolated from gastric cancer tissue correlated well with polymorphism, H. pylori infection, increased PGII level, and pathway for bacteria cell entry into the host. Conclusions: Serum PGII levels depend in part on an interaction between H. pylori and host miRNA genotypes, which may interfere with the cut-off of PGI/PGII ratio used to identify persons at risk of gastric cancer. Results reported new findings regarding the relation among H. pylori, PGII-related host polymorphism, and genes involved in this interaction in the gastric cancer setting.

• Helicobacter pylori
• PGC
• RNAs
• gastric cancer
• polymorphisms
• serum pepsinogen II

• EMT
• TCF12
• glioblastoma
• microRNA
• p53

• Adult
• Apoptosis Regulatory Proteins/genetics
• Case-Control Studies
• Female
• Genetic Loci
• Genome-Wide Association Study
• HIV Infections/complications
• HIV Infections/genetics
• HIV Infections/pathology
• HIV Infections/virology
• Haplotypes
• Humans
• Introns
• Kruppel-Like Transcription Factors/genetics
• MicroRNAs/genetics
• Middle Aged
• Models, Genetic
• Nigeria
• Papillomaviridae/growth & development
• Papillomaviridae/pathogenicity
• Papillomavirus Infections/complications
• Papillomavirus Infections/genetics
• Papillomavirus Infections/pathology
• Papillomavirus Infections/virology
• Polymorphism, Single Nucleotide
• Receptors, Cytoplasmic and Nuclear/genetics
• Risk Factors
• Uterine Cervical Neoplasms/complications
• Uterine Cervical Neoplasms/genetics
• Uterine Cervical Neoplasms/pathology
• Uterine Cervical Neoplasms/virology
• Uterine Cervical Dysplasia/complications
• Uterine Cervical Dysplasia/genetics
• Uterine Cervical Dysplasia/pathology
• Uterine Cervical Dysplasia/virology

• U54 HG006947 NHGRI NIH HHS
• IRG-18-160-16 American Cancer Society
• 1D43CA153792–01 National Institutes of Health (US)
• D43 CA153792 NCI NIH HHS
• 1U54HG006947 NIH HHS
• National Institutes of Health

Gastric carcinoma (GC) is currently one of the most common malignant tumors of the digestive system, and gastric precancerous lesions play a vital role in studying the mechanism of GC. Multiple microRNAs (miRNAs) have been documented to be potential biomarkers to indicate progression of gastric precancerous lesions. In this study, we explained the anti-cancer effect of miR-365 in gastric precancerous lesions via regulation of the TLR4/IRF3/YAP/CDX2 axis.

miR-365, TLR4, CDX2 and IPF3 expression was determined in GC and atrophic gastritis tissues and cells. After transfection of shRNA and overexpression plasmids, in vitro experiments detected the alteration of cell viability, apoptosis and inflammatory factors. Bioinformatics analysis, Co-IP and dual luciferase reporter gene assay were conducted to evaluate the binding between miR-365 and TLR4 as well as IRF3 and YAP. Rat models were established to explore the effect of the miR-365 and TLR4 on gastric precancerous lesions.

miR-365 was poorly expressed in GC and atrophic gastritis tissues and GC cell lines, while TLR4, CDX2 and IRF3 were overexpressed. Of note, miR-365 was indicated to target TLR4 and thereby suppressed cancer progression and increased hemoglobin content. Interestingly, silencing of TLR4 was accompanied by decreased IRF3 phosphorylation and reduced expression with less binding between CDX2 and IRF3. Downregulation of YAP resulted in declined CDX2 expression in cancer cells. Moreover, the inhibitory role of miR-365 was further confirmed in animal models.

Taken together, miR-365-mediated TLR4 inhibition reduces IRF3 phosphorylation and YAP-mediated CDX2 transcription to impede progression of gastric precancerous lesions.

• CDX2
• Gastric precancerous lesions
• IRF3
• MicroRNA-365
• TLR4
• YAP

As one of the most common malignant gastrointestinal tumors, gastric cancer (GC) has a high incidence and poor prognosis. Cisplatin (DDP) is often used as chemotherapy for advanced GC; however, the high incidence of drug resistance remains a problem. The use of several anti-tumor drugs as combined chemotherapy is an effective strategy. Hesperetin has anti-tumor ability via its pro-apoptotic effect on various human cancers, both in vitro and in vivo, with no significant toxicity. However, a combination of DDP and hesperetin in GC has not been reported. The present study aimed to investigate the in vitro and in vivo chemosensitization effect and mechanism of hesperetin-augmented DDP-induced apoptosis of GC. The proliferation of GC ty -60cells was inhibited significantly in a time and dose-dependent manner by combined treatment of DDP with hesperetin. Hesperetin markedly increased DDP-induced apoptosis of GC cell lines. In a xenograft tumor mouse model, markedly better tumor suppression was observed after treatment with DDP plus hesperetin compared with that of either agent alone. Additionally, the combination of DDP and hesperetin remarkably increased the expression levels of phosphatase and tensin homolog (PTEN) and Cytochrome C (Cyt C), and significantly decreased the levels of phosphorylated protein kinase B (p-AKT) and CyclinD1. DDP and hesperetin also induced significant increases in apoptosis inducing factor (AIF), BCL2 associated X, apoptosis regulator (BAX), cleaved caspase-9, and cleaved caspase-3, and decreased B-cell lymphoma 2 (BCL2), caspase-9, and caspase-3 levels. Thus, we demonstrated that hesperetin could inhibit the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling pathway and induce the mitochondrial pathway via upregulating PTEN expression, thereby significantly enhancing DDP’s anti-tumor effect on GC. Hesperetin is a potential chemotherapeutic agent for GC and merits further clinical investigation.

• apoptosis
• cisplatin
• gastric cancer
• hesperetin
• mitochondrial pathway
• phosphatase and tensin homolog

• BEND cells
• Endometritis
• HMGB1/NF-κB
• LPS
• miR-505

• PI3K/Akt
• gastric cancer
• growth
• metastasis
• phosphatase and tensin homolog (PTEN)

• NA Ministry of Education - Singapore
• NMRC/OFIRG/0020/2016 National Medical Research Council

Gastric cancer (GC) is one of the most common and fatal malignancies worldwide. MicroRNAs (miRNAs) play a critical role in tumor initiation, proliferation, and metastasis of gastric cancer. miR193b has been identified as a tumor suppressor in a variety of tumor types; however, its role in gastric cancer is yet to be determined. Here, we found a significant downregulation of miR193b expression in both human gastric cancer tissues (p < 0.05) and human gastric cancer cell lines (p < 0.01). Furthermore, the expression level of miR193b correlated with the tumor type, tumor size, and clinical stage (p < 0.05). In vitro, miR193b overexpression inhibited cell survival and induced apoptosis in GC cell lines, indicating that miR193b plays a role in the development of gastric cancer. KRAS was verified as the target of miR193b, and KRAS overexpression attenuated miR193b-induced apoptosis (p < 0.05). Moreover, we found that the Akt pathway negatively regulated miR193b, also affecting apoptosis. Further analyses indicated that PIK3CA mutation and KRAS amplification are two mutually exclusive pathways (p < 0.01), and we hypothesize that both two pathways could result in the carcinogenic overactivation of KRAS. Thus, our results suggest that the Akt-miR193b-KRAS axis may act as a mechanism affecting apoptosis in gastric cancer cells.

• CRC
• miRNA
• miRNA-145
• miRNA-365
• sponges

Hypoxia-exposed lung cancer-released exosomal microRNA-23a (miR-23a) has been shown to enhance angiogenesis as well as vascular permeability, contributing to the close correlation between exosomal miR-23a and tumorigenesis. The current study aimed to investigate whether gastric cancer (GC) cell-derived exosomal miR-23a could induce angiogenesis and to elucidate the potential mechanisms associated with the process. Differentially expressed miRNAs in GC were initially screened from the Gene Expression Omnibus database. Target genes were selected following miRNA-mRNA prediction and subsequently verified by dual luciferase reporter assay. RT-qPCR was conducted to detect miR-23a and PTEN expression in GC tissues, cells and exosomes. Human umbilical venous endothelial cells (HUVECs) were co-cultured with GC cell-derived exosomes to assess the angiogenesis mediated by exosomes in vitro. Additionally, PTEN was overexpressed in HUVECs to analyze the mechanism by which miR-23a regulates angiogenesis. miR-23a was highly expressed in GC tissues and cells and GC cell-derived exosomes. Angiogenesis was promoted by the co-culture of HUVECs and GC cells-derived exosomes, as evidenced by the increased expression of VEGF but decreased expression of TSP-1. PTEN was targeted by miR-23a and was lowly expressed in GC tissues. In a co-culture system, miR-23a carried by GC cells-derived exosomes promoted angiogenesis via the repression of PTEN. Collectively, GC cell-derived exosomal miR-23a could promote angiogenesis and provide blood supply for growth of GC cells. This study contributes to advancement of miRNA-targeted therapeutics.

• AKT pathway
• PTEN
• angiogenesis
• exosome
• gastric cancer
• microRNA-23a

As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out.

In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses.

The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo.

This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

• Compound Kushen injection
• Gastric Cancer
• Network pharmacology

• CDC25A
• CircRNA_104433
• cell proliferation
• circular RNA profiling
• gastric cancer
• miR-497-5p

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Thus, identification of the mechanisms involved in the progression of CRC has become a crucial element of facilitating early CRC diagnosis and targeted therapy for patients with advanced CRC. Currently, Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a type of histidine phosphatase protein, has been confirmed as a tumor suppressor in hepatocellular carcinoma (HCC) and cervical cancer. However, the functions and molecular mechanisms underlying LHPP in CRC remain undefined. The present study revealed that dysregulation of LHPP was frequently observed in CRC tissues and was positively correlated with tumor severity and poor prognosis. Functional experiments demonstrated that overexpression of LHPP impeded CRC cell growth and proliferation in vitro, and was associated with a change in p53 expression and PI3K/AKT activity. In contrast, silencing of LHPP significantly promoted cell growth and proliferation by modulating the PI3K/AKT signaling pathway. Notably, the anti-CRC effects of LHPP were also observed in nude mouse in vivo experiments. Overall, the data obtained in the present study suggested that LHPP may be exploited as a diagnostic and prognostic candidate for patients with CRC.

• AKT/NF-κB
• ROS
• endometritis
• lipopolysaccharide
• miR-488

CDK4/6 inhibitors are effective against cancer cells expressing the tumor suppressor RB1, but not RB1-deficient cells, posing the challenge of how to target RB1 loss. In triple-negative breast cancer (TNBC), RB1 and PTEN are frequently inactivated together with TP53. We performed kinome/phosphatase inhibitor screens on primary mouse Rb/p53-, Pten/p53-, and human RB1/PTEN/TP53-deficient TNBC cell lines and identified CDC25 phosphatase as a common target. Pharmacological or genetic inhibition of CDC25 suppressed growth of RB1-deficient TNBC cells that are resistant to combined CDK4/6 plus CDK2 inhibition. Minimal cooperation was observed in vitro between CDC25 antagonists and CDK1, CDK2, or CDK4/6 inhibitors, but strong synergy with WEE1 inhibition was apparent. In accordance with increased PI3K signaling following long-term CDC25 inhibition, CDC25 and PI3K inhibitors effectively synergized to suppress TNBC growth both in vitro and in xenotransplantation models. These results provide a rationale for the development of CDC25-based therapies for diverse RB1/PTEN/TP53-deficient and -proficient TNBCs.

Liu et al. report that inhibition of the protein phosphatase CDC25 kills diverse triple-negative breast cancer (TNBC) cells. Moreover, CDC25 antagonists cooperate with other drugs, such as PI3K inhibitors, to efficiently suppress growth of human TNBC engrafted into mice.

• CDC25
• CHK1
• PTEN
• RB1
• TP53
• WEE1
• basal-like breast cancer
• checkpoint control
• therapy
• triple negative breast cancer

Osteoarthritis (OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus. Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^ERT2 developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice. Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore, inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA.

• Bone
• Physiology

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.

• ESCC
• FGFR2
• miR-671-5p
• tumor progression

• TRIM25
• apoptosis
• microRNA-365
• non-small-cell lung cancer
• proliferation

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and it can be locally invasive and metastatic to distant sites. MicroRNAs (miRNAs or miRs) are endogenous, small, non-coding RNAs of 19–25 nucleotides in length, that are involved in regulating gene expression at a post-transcriptional level. MicroRNAs have been implicated in diverse biological functions and diseases. In cancer, miRNAs can proceed either as oncogenic miRNAs (onco-miRs) or as tumor suppressor miRNAs (oncosuppressor-miRs), depending on the pathway in which they are involved. Dysregulation of miRNA expression has been shown in most of the tumors evaluated. MiRNA dysregulation is known to be involved in the development of cutaneous squamous cell carcinoma (CSCC). In this review, we focus on the recent evidence about the role of miRNAs in the development of CSCC and in the prognosis of this form of skin cancer.

• cutaneous squamous cell carcinoma
• miRNAs
• skin cancer

• Aged
• Animals
• Apoptosis/drug effects
• Cell Movement
• Cell Proliferation
• Disease Progression
• Disulfides/pharmacology
• Female
• Humans
• Imidazoles/pharmacology
• Lentivirus/metabolism
• Male
• Mice, Nude
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis
• PTEN Phosphohydrolase/metabolism
• Prognosis
• Proportional Hazards Models
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction/drug effects
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Thioredoxins/metabolism
• Up-Regulation/drug effects

• FADD
• Foxo3a
• chemosensitivity
• gastric cancer
• miR-633

• Bioinformatics
• Prognosis
• TCGA
• Uveal melanoma

• E-cadherin
• Lgr5+ stem cells
• apoptosis
• gastric epithelium
• homeostasis

Radiation is utilized in the therapy of more than 50% of cancer patients. Unfortunately, many malignancies become resistant to radiation over time. We investigated the hypothesis that one method of a cancer cell's ability to survive radiation occurs through cellular communication via exosomes. Exosomes are cell-derived vesicles containing DNA, RNA, and protein. Three properties were analyzed: 1) exosome function, 2) exosome profile and 3) exosome uptake/blockade. To analyze exosome function, we show radiation-derived exosomes increased proliferation and enabled recipient cancer cells to survive radiation in vitro. Furthermore, radiation-derived exosomes increased tumor burden and decreased survival in an in vivo model. To address the mechanism underlying the alterations by exosomes in recipient cells, we obtained a profile of radiation-derived exosomes that showed expression changes favoring a resistant/proliferative profile. Radiation-derived exosomes contain elevated oncogenic miR-889, oncogenic mRNAs, and proteins of the proteasome pathway, Notch, Jak-STAT, and cell cycle pathways. Radiation-derived exosomes contain decreased levels of tumor-suppressive miR-516, miR-365, and multiple tumor-suppressive mRNAs. Ingenuity pathway analysis revealed the most represented networks included cell cycle, growth/survival. Upregulation of DNM2 correlated with increased exosome uptake. To analyze the property of exosome blockade, heparin and simvastatin were used to inhibit uptake of exosomes in recipient cells resulting in inhibited induction of proliferation and cellular survival. Because these agents have shown some success as cancer therapies, our data suggest their mechanism of action could be limiting exosome communication between cells. The results of our study identify a novel exosome-based mechanism that may underlie a cancer cell's ability to survive radiation.

• exosomes
• glioblastoma
• glioma
• radiation
• resistance

• EZH2
• FOS
• endometrial cancer
• microRNA-365
• paclitaxel