• Gut microbiota
• Metabolites
• Multiple myeloma
• Urolithin

• Humans
• Multiple Myeloma/drug therapy
• Multiple Myeloma/microbiology
• Animals
• Mice
• Coumarins
• Bortezomib/therapeutic use
• Bortezomib/pharmacology
• Retrospective Studies
• Gastrointestinal Microbiome/drug effects
• Male
• RNA, Ribosomal, 16S/genetics
• Female
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Aged
• Middle Aged
• Xenograft Model Antitumor Assays

• PMPTA22/00088 ISCIII/CDTI
• PMPTA22/00088 ISCIII/CDTI
• FPU19/04933 Ministry of Science, Innovation and Universities of Spain
• Accelerator Award Fundación Científica Asociación Española Contra el Cáncer
• IDEAS20014LINA Fundación Científica Asociación Española Contra el Cáncer
• PID2021-123056OA-I00 MCIN/AEI/10.13039/501100011033
• Sociedad Española de Hematología y Hemoterapia
• CRIS Cancer Foundation
• CIBERONC

• CircPDE5A
• Circular RNA
• Esophageal squamous cell carcinoma
• Nanoparticles
• PI3K/AKT pathway

• Animals
• Female
• Humans
• Male
• Mice
• Middle Aged
• Cell Line, Tumor
• Cell Proliferation
• Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism
• Cyclic Nucleotide Phosphodiesterases, Type 5/genetics
• Disease Progression
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/genetics
• Esophageal Squamous Cell Carcinoma/pathology
• Esophageal Squamous Cell Carcinoma/metabolism
• Esophageal Squamous Cell Carcinoma/genetics
• Mice, Nude
• Phosphatidylinositol 3-Kinases/metabolism
• Prognosis
• Proto-Oncogene Proteins c-akt/metabolism
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Signal Transduction
• Ubiquitin Thiolesterase/metabolism
• Ubiquitin Thiolesterase/genetics
• Ubiquitination

• 82371847 National Natural Science Foundation of China
• 82073121 National Natural Science Foundation of China
• 82002417 National Natural Science Foundation of China
• 202103000063 Guangzhou Municipal Science and Technology Project

• ER stress
• SYVN1
• cell cycle regulation
• endoplasmic reticulum-associated degradation (ERAD)
• esophageal squamous cell carcinoma
• quantitative proteomics

• Dietary selenium
• Mice
• Oxidative stress
• Sperm quality
• Testis

• Male
• Animals
• Mice
• Testis
• Selenium/metabolism
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Caspase 3/metabolism
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Sperm Motility
• Semen/metabolism
• Oxidative Stress
• Apoptosis
• Signal Transduction
• Cell Proliferation

• National Natural Science Foundation of China
• Project 333 of Jiangsu Province
• Natural Science Foundation of Jiangsu Province

• PI3K/AKT/mTOR signaling pathway
• esophageal squamous cell carcinoma (ESCC)
• eukaryotic translation initiation factors (eIFs)
• inhibitors
• therapeutic target

Esophageal squamous cell carcinoma (ESCC), is the most common type of esophageal cancer worldwide, mainly occurring in the Asian esophageal cancer belt, including northern China, Iran, and parts of Africa. Phosphatidlinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is one of the most important cellular signaling pathways, which plays a crucial role in the regulation of cell growth, differentiation, migration, metabolism and proliferation. In addition, mutations in some molecules of PI3K/Akt/mTOR pathway are closely associated with survival and prognosis in ESCC patients. A large number of studies have found that there are many molecules in ESCC that can regulate the PI3K/Akt/mTOR pathway. Overexpression of these molecules often causes aberrant activation of PI3K/Akt/mTOR pathway. Currently, several effective PI3K/Akt/mTOR pathway inhibitors have been developed, which can play anticancer roles either alone or in combination with other inhibitors. This review mainly introduces the general situation of ESCC, the composition and function of PI3K/Akt/mTOR pathway, and regulatory factors that interact with PI3K/Akt/mTOR signaling pathway. Meanwhile, mutations and inhibitors of PI3K/Akt/mTOR pathway in ESCC are also elucidated.

• ESCC
• PI3K/Akt/mTOR pathway
• drug resistance
• inhibitor
• mutation

• Animals
• Biocompatible Materials/chemistry
• Biocompatible Materials/pharmacology
• Blood Vessels/drug effects
• Blood Vessels/physiology
• Blotting, Western
• Ceramics/chemistry
• Ceramics/pharmacology
• Connexin 43/metabolism
• Human Umbilical Vein Endothelial Cells/drug effects
• Human Umbilical Vein Endothelial Cells/metabolism
• Human Umbilical Vein Endothelial Cells/physiology
• Humans
• Male
• Mice, Inbred ICR
• Microscopy, Electron, Scanning
• Pyroptosis/drug effects
• Reactive Oxygen Species/metabolism
• Signal Transduction/drug effects
• Spectroscopy, Fourier Transform Infrared
• Wound Healing/drug effects
• Mice

• Animal model
• Dermal fibroblast
• Heterogeneity
• Pig
• Proliferating cell nuclear antigen
• Skin

• Animals
• Cell Proliferation
• Fibroblasts
• Humans
• Proliferating Cell Nuclear Antigen/metabolism
• Skin/metabolism
• Swine

• AKT
• FGD1
• PI3K
• biomarker
• melanoma
• prognostic factor

• Animals
• Apoptosis/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Guanine Nucleotide Exchange Factors/metabolism
• Humans
• Lung Neoplasms/secondary
• Melanoma/genetics
• Melanoma/pathology
• Mice, Inbred BALB C
• Mice, Nude
• Phosphatidylinositol 3-Kinases/metabolism
• Prognosis
• Proto-Oncogene Proteins c-akt/metabolism
• Skin Neoplasms/genetics
• Skin Neoplasms/pathology
• Tumor Stem Cell Assay
• Up-Regulation/genetics
• Mice

• Cancer risk
• Meta-analysis
• RPTOR gene
• Single nucleotide polymorphism (SNP)
• mLST8 gene
• mTOR gene

Esophageal squamous cell carcinoma (ESCC) is a life-threatening digestive tract malignancy with no known curative treatment. This study aimed to investigate the antineoplastic effects of omipalisib and its underlying molecular mechanisms in ESCC using a high throughput screen.

MTT assay and clone formation were used to determine cell viability and proliferation. Flow cytometry was conducted to detect cell cycle distribution and apoptosis. Global gene expression and mRNA expression levels were determined by RNA sequencing and real-time PCR, respectively. Protein expression was evaluated in the 4 ESCC cell lines by Western blot analysis. Finally, a xenograft nude mouse model was used to evaluate the effect of omipalisib on tumor growth in vivo.

In the pilot screening of a 1404-compound library, we demonstrated that omipalisib markedly inhibited cell proliferation in a panel of ESCC cell lines. Mechanistically, omipalisib induced G₀/G₁ cell cycle arrest and apoptosis. RNA-seq, KEGG, and GSEA analyses revealed that the PI3K/AKT/mTOR pathway is the prominent target of omipalisib in ESCC cells. Treatment with omipalisib decreased expression of p-AKT, p-4EBP1, p-p70S6K, p-S6, and p-ERK, therefore disrupting the activation of PI3K/AKT/mTOR and ERK signaling. In the nude mouse xenograft model, omipalisib significantly suppressed the tumor growth in ESCC tumor-bearing mice without obvious adverse effects.

Omipalisib inhibited the proliferation and growth of ESCC by disrupting PI3K/AKT/mTOR and ERK signaling. The present study supports the rationale for using omipalisib as a therapeutic approach in ESCC patients. Further clinical studies are needed.

Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both in vitro and in vivo. Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC.

• 4EBP-1, E binding protein-1
• AKT
• AKT, protein kinase B (PKB)
• ESCC, esophageal squamous cell carcinoma
• Esophageal squamous cell carcinoma
• FDA, U.S. Food and Drug Administration
• H&E staining, hematoxylin and eosin staining
• IC50, half maximal inhibitory concentration
• PI3K, phosphatidylinositol 3 kinase
• RAD001
• RICTOR
• RICTOR, rapamycin-insensitive companion of mTOR
• TNM, tumor-node-metastasis
• TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling
• mTOR, mammalian target of rapamycin
• mTORC1, mTOR complex 1
• mTORC2, mTOR complex 2
• p70S6K, p70 ribosomal S6 kinase-1
• pp242
• rapalogs, rapamycin and its analogs

• B-cell Burkitt’s lymphoma
• B-cell acute lymphoblastic leukemia
• K313
• apoptosis
• autophagy blockage
• cell cycle arrest
• mitochondrial pathway

• Animals
• Antineoplastic Agents, Phytogenic/pharmacology
• Apoptosis/drug effects
• Autophagy/drug effects
• Benzoxazoles/chemistry
• Benzoxazoles/pharmacology
• Cell Cycle Checkpoints/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Humans
• Leukocytes, Mononuclear
• Lymphoma/drug therapy
• Lymphoma/genetics
• Lymphoma/pathology
• Mice
• RAW 264.7 Cells
• Ribosomal Protein S6 Kinases, 70-kDa/genetics
• Signal Transduction/drug effects
• TOR Serine-Threonine Kinases/genetics

• PI3K/AKT/mTOR pathway
• esophageal cancer
• microRNAs
• rapamycin
• transcription
• translation.

• Akt
• Merkel cell carcinoma
• PI3K
• basal cell carcinoma
• mTOR
• melanoma
• phytochemicals
• skin cancers
• squamous cell carcinoma
• targeted therapy

• Animals
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Biological Products/pharmacology
• Biological Products/therapeutic use
• Clinical Trials as Topic
• Humans
• Molecular Targeted Therapy
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction/drug effects
• Skin Neoplasms/drug therapy
• Skin Neoplasms/metabolism
• TOR Serine-Threonine Kinases/metabolism

• P30 AR066524 NIAMS NIH HHS

• EIF2 pathway
• LC/MS
• lovastatin
• mTOR pathway
• nasopharyngeal carcinoma

• Henoch-Schönlein purpura nephritis
• IgA1
• children
• human mesangial cells
• transferrin receptor

• 7-O-geranylquercetin
• Breast cancer
• Interleukin-10
• Survivin
• siRNA

• Gene delivery
• Liver injury
• Peptide cationic liposome
• Pulmonary inflammation
• Toxicology

• AML12 liver cells
• hepatotoxicity
• matrine
• mice
• oxymatrine
• radix Sophorae tonkinensis

Hypopharyngeal carcinoma (HPC) is an aggressive malignancy with the worst prognosis among all head and neck cancers. MicroRNAs (miRNAs) are involved in the development of many human cancers, and may function as oncogenes or tumor suppressors. The present study aimed to evaluate the effects of miRNA (miR)-194-5p on the proliferation and invasion of HPC cells and to identify the potential regulatory mechanism. First, miR-194-5p and Smad ubiquitin regulatory factor 1 (SMURF1) expression levels were examined in HPC tissues. Subsequently, to explore the effects of miR-194-5p on SMURF1, a dual-luciferase reporter gene assay was performed to verify the target relationship. To define the role of miR-194-5p in HPC progression, miR-194-5p upregulation and depletion were used to evaluate its effects on cell viability, invasion and migration. SMURF1 silencing and rapamycin [an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway] treatment were also used to analyze the regulatory mechanism in HPC. Finally, tumor growth was assessed in xenografted tumors in nude mice. SMURF1 was demonstrated to be highly expressed, whereas miR-194-5p was poorly expressed in HPC tissues; SMURF1 was identified as a target gene of miR-194-5p. FaDu hypopharyngeal squamous cell carcinoma cells treated with miR-194-5p mimics exhibited decreased viability, invasion and migration. The results indicated that miR-194-5p may inactivate the mTOR signaling pathway by targeting SMURF1. In addition, the in vivo experiments further verified these regulatory effects. These data suggested that miR-194-5p-targeted SMURF1 inhibition may be involved in the disruption of HPC progression through the repression of the mTOR signaling pathway.

• Biological activity
• Characterization
• Dictyopteris divaricata seaweed polysaccharide

• Animals
• Biphenyl Compounds/chemistry
• Hydroxyl Radical/chemistry
• Immunologic Factors/chemistry
• Immunologic Factors/isolation & purification
• Immunologic Factors/pharmacology
• Mice
• Monosaccharides/analysis
• Phaeophyceae/chemistry
• Picrates/chemistry
• Polysaccharides/chemistry
• Polysaccharides/isolation & purification
• Polysaccharides/pharmacology
• RAW 264.7 Cells
• Seaweed/chemistry
• Sulfates/chemistry

• Invasion
• Proliferation
• RhoA
• Squamous cell carcinoma
• miR-340

• Esophageal squamous cell carcinoma
• FLI-06
• LSD1
• Notch

This study aimed to elucidate the effect of tryptophan (Trp) on gut hormone secretion as well as the roles of the calcium-sensing receptor (CaSR) and its downstream signaling pathway in gut hormone secretion by assessing swine duodenal perfusion in vitro. Swine duodenum was perfused with Krebs-Henseleit buffer as a basal solution. Various concentrations (0, 10, and 20 mM) of Trp were applied to investigate its effect on gut hormone secretion. A CaSR antagonist was used to detect the involvement of CaSR and its signal molecules. The 20 mM Trp concentration promoted the secretion of cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP), elevated the mRNA level of CaSR, and upregulated the protein levels of CaSR, protein kinase C (PKC), and inositol trisphosphate receptor (IP3R). However, NPS 2143, an inhibitor of CaSR, attenuated the CCK and GIP release, reduced the mRNA level of CaSR, and decreased the protein levels of CaSR, PKC, and IP3R with 20 mM Trp perfusion. The results indicate that CCK and GIP secretion can be induced by Trp in swine duodenum in vitro, and the effect is mediated by CaSR and its downstream signal molecules PKC and IP3R.

• calcium-sensing receptor
• gut hormone
• signaling pathway
• swine
• tryptophan

• Eriocheir sinensis
• Hematopoietic tissue
• Mitochondrial complexes I
• N-acetyl-l-cysteine (NAC)
• Reactive oxygen species (ROS)
• Transcriptome sequencing

• Acetylcysteine/pharmacology
• Animals
• Brachyura/physiology
• Cell Differentiation
• Cells, Cultured
• Energy Metabolism
• Gene Expression Profiling
• Gene Ontology
• Hematopoiesis
• Hematopoietic Stem Cells/physiology
• Hemocytes/physiology
• Mitochondria/metabolism
• NADH Dehydrogenase/genetics
• NADH Dehydrogenase/metabolism
• Oxidation-Reduction
• Reactive Oxygen Species/metabolism

PSMD7, a 19S proteasome subunit, is overexpressed in most carcinoma cells. It forms a dimer with PSMD14 that functions in the removal of attached ubiquitin chain. However, there is little knowledge about the cellular mechanism of PSMD7 and its exact biological function, especially in cancer cells. In this study, we explored the role of PSMD7 in proliferation, cell cycle, apoptosis, and proteasomal proteolysis in the esophageal squamous cell carcinoma (ESCC) cell line EC9706. Our results showed that PSMD7 was highly expressed in ESCC cells. Downregulation of PSMD7 by lentivirus‐mediated shRNA led to decreased proliferation, increased cell apoptosis, and reduced proteasomal function. Notably, lower expression level of mTOR and p70S6K and suppressed activity of mTOR/p70S6K pathway were detected after PSMD7 downregulation. By contrast, increased expression of p‐mTOR^Ser2448 and p‐p70S6K^{Thr421/Ser424} was discovered upon PSMD7 overexpression in Het‐1A cells. Furthermore, PSMD7 downregulation contributed to decelerated tumor growth, inhibition of proteasomal function, induced cell apoptosis and attenuated activity of mTOR/p70S6K pathway in vivo. These findings suggest that PSMD7 and the mTOR/p70S6K pathway may be a promising candidate for developing therapies for ESCC.

• PSMD7
• apoptosis (ESCC)
• esophageal squamous cell carcinoma
• mTOR/p70S6K pathway
• tumorigenesis

• Eutypella sp.
• arctic fungi
• bioactivity
• pimarane diterpenes
• secondary metabolites

As a naturally occurring inhibitor of mTOR, accumulated evidence has suggested that DEPTOR plays a pivotal role in suppressing the progression of human malignances. However, the function of DEPTOR in the development of esophageal squamous cell carcinoma (ESCC) is still unclear. Here we report that the expression of DEPTOR is significantly reduced in tumor tissues derived from human patients with ESCC, and the downregulation of DEPTOR predicts a poor prognosis of ESCC patients. In addition, we found that the expression of DEPTOR negatively regulates the tumorigenic activities of ESCC cell lines (KYSE150, KYSE510 and KYSE190). Furthermore, ectopic DEPTOR expression caused a significant suppression of the cellular proliferation, migration and invasion of KYSE150 cells, which has the lowest expression level of DEPTOR in the three cell lines. Meanwhile, CRISPR/Cas9 mediated knockout of DEPTOR in KYSE-510 cells significantly promoted cellular proliferation, migration and invasion. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic DEPTOR expression as compared to untreated KYSE150 cells, and was markedly enhanced in DEPTOR knockout KYSE-510 cells. Biochemical studies revealed that overexpression of DEPTOR led to the suppression of AKT/mTOR pathway as evidenced by reduced phosphorylation of AKT, mTOR and downstream SGK1, indicating DEPTOR might control the progression of ESCC through AKT/mTOR signaling pathway. Thus, these findings, for the first time, demonstrated that DEPTOR inhibits the tumorigenesis of ESCC cells and might serve as a potential therapeutic target or prognostic marker for human patients with ESCC.

• DEPTOR
• esophageal squamous cell carcinoma
• mTOR
• proliferation

As a widely grown economic crop, cotton is the major oil and protein resource for human and livestock. But the highly toxic of gossypol in cottonseed severely restricts its effective utilization, consequently creating huge resource waste. Previous studies have shown the male germline stem cells were the most vulnerable cells in gossypol damages, but the mechanism was still unclear. We found gossypol induced cell viability decline resulted from apoptosis. And the increase of Caspase-9 activity in gossypol treatment hinted the mitochondrial apoptosis. So the mitochondrial dysfunction was confirmed by the decreased mitochondrial membrane potential and ATP concentration. We found the higher intracellular H₂O₂ level did not accompany with the O₂^·- associated increase in gossypol-treated, which indicated that gossypol obstructed the intracellular reactive oxygen species (ROS) elimination. Manipulated gossypol-induced H₂O₂ level by H₂O₂ and α-lipoic acid, we demonstrated that the mitochondrial dysfunction resulted from the excessive intracellular H₂O₂. Treated with Apogossypolone (ApoG2), an aldehyde group removed derivative of gossypol, the GSH/GSSG ratio and H₂O₂ did not decrease. ApoG2 also did not cause the mitochondrial apoptosis. So the aldehyde group is key factor in gossypol cytotoxicity. We respectively detected the NAD⁺/NADH ratio, SIRT1 activity, the relative protein level and apoptosis. Comparing with the specific inhibitors groups, the data illustrated that gossypol induced apoptosis through SIRT1-P53-PUMA pathway. This study helped to overcome barriers of gossypol cytotoxicity, which is crucial in feed and food use of cottonseed. This also provides a reference for the gossypol derivatives using in male contraception and anticancer.

• apoptosis
• gossypol
• male germline stem cell (mGSCs)
• mitochondrion
• reactive oxygen species (ROS)

Methylglyoxal (MG) accumulation has been observed in human cerebrospinal fluid and body tissues under hyperglycaemic conditions. Recent research has demonstrated that MG-induces neuronal cell apoptosis, which promotes the development of diabetic encephalopathy. Our previous animal study has shown that luteolin, a natural flavonoid, attenuates diabetes-associated cognitive dysfunction. To further explore the neuroprotective properties of luteolin, we investigated the inhibitive effect of luteolin on MG-induced apoptosis in PC12 neuronal cells. We found that MG inhibited cell viability in a dose-dependent manner and induced apoptosis in PC12 cells. Pretreatment with Luteolin significantly elevated cell viability, reduced MG-induced apoptosis, inhibited the activation of the mTOR/4E-BP1 signaling pathway, and decreased pro-apoptotic proteins, Bax, Cytochrome C as well as caspase-3. Furthermore, we found that pretreatment with the mTOR inhibitor, rapamycin, significantly reduced the expression of the pro-apoptotic protein Bax. Therefore, these observations unambiguously suggest that the inhibitive effect of Luteolin against MG-induced apoptosis in PC12 cells is associated with inhibition of the mTOR/4E-BP1 signaling pathway.

• Cell regeneration
• Crassostrea gigas
• Enhanced immune response
• Gill
• Hematopoiesis
• Immune priming

• Animals
• Cell Self Renewal
• Crassostrea/immunology
• GATA3 Transcription Factor/genetics
• GATA3 Transcription Factor/metabolism
• Gills/immunology
• Hematopoiesis
• Hemocytes/physiology
• Immunity
• Immunization
• Immunization, Secondary
• Phagocytosis
• Reactive Oxygen Species/metabolism
• Regeneration
• Vibrio/immunology
• Vibrio Infections/immunology

• Akt
• CCI-779 (PubChem CID: 6918289)
• Esophageal squamous cell carcinoma
• Oridonin
• Oridonin (PubChem CID: 102004437)
• RAD001 (PubChem CID: 6442177)
• Rapamycin
• Rapamycin (PubChem CID: 5284616)
• mTOR

miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC). The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC. The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown. In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated. Dual-luciferase reporter assay demonstrated that HMGA2 is a target of miR-195. MTT assay and flow cytometry revealed that miR-195 overexpression inhibited cell proliferation and induced apoptosis by targeting HMGA2. We also found that HMGA2 restored the inhibitory effect of miR-195 on phosphorylation of mTOR and p70S6K. Furthermore, rapamycin, a specific inhibitor of the mTOR/p70S6K signaling pathway, decreased the levels of Ki-67 and Bcl-2/Bax ratio, inhibited cell proliferation, and promoted apoptosis in EC cells. In conclusion, upregulation of miR-195 significantly suppressed cell growth and induced apoptosis of EC cells via suppressing the mTOR/p70s6k signaling pathway by targeting HMGA2.

The aim of the study was to examine the expression of mammalian target of rapamycin (mTOR)/70S6K signaling pathway in pathological scar fibroblasts and the effects of resveratrol (Res) intervention. The mTOR and 70S6K in pathological scar and normal skin fibroblasts were detected by immunofluorescence following treatment with different concentrations of Res. RT-PCR and western blot analysis were used to detect the expression of mTOR and 70S6K mRNA and protein, respectively. Immunofluorescence showed that the expression of 70S6K and mTOR was significantly enhanced in pathological scar fibroblasts, and mainly expressed in the nucleus, but not in normal skin fibroblasts. RT-PCR and western blot analysis showed that after different concentrations of Res treatments, the mTOR and 70S6K mRNA and protein expression significantly (P<0.05) decreased in a dose-dependent manner. In conclusion, the expression of mTOR/70S6K signaling pathway in pathological scar fibroblasts was significantly enhanced. Res can downregulate the expression of mTOR and 70S6K to achieve the inhibition of pathological scar fibroblast proliferation.

• Actin acetylation
• Calreticulin
• Human microvascular endothelial cell
• Microwave radiation

• Acetylation/drug effects
• Acetylation/radiation effects
• Actin Cytoskeleton/drug effects
• Actin Cytoskeleton/radiation effects
• Actins/metabolism
• Antigens, CD/metabolism
• Cadherins/metabolism
• Calreticulin/genetics
• Calreticulin/metabolism
• Calreticulin/pharmacology
• Cell Line
• Cell Movement
• Cell Survival/drug effects
• Cell Survival/radiation effects
• Endothelial Cells/cytology
• Endothelial Cells/metabolism
• Histone Acetyltransferases/metabolism
• Humans
• Microscopy, Fluorescence
• Microwaves
• Recombinant Proteins/biosynthesis
• Recombinant Proteins/pharmacology

• the National Natural Science Foundation of China

Increased expression of Ets2 is reported upregulated in esophageal squamous cell carcinoma tissue. However, the function of Ets2 in carcinogenesis of ESCC is poorly understood. Here, the rise of Ets2 was confirmed in ESCC cells and Ets2 depletion by RNA interference promotes cell apoptosis, inhibits cell proliferation, attenuates cell invasion and induces cell cycle G0/G1 arrest in vitro. Moreover, in vivo, Xenograft mouse model studies showed Ets2 knockdown inhibits tumor formation and metastasis significantly. Furthermore, Ets2 depletion inactivates the mTOR/p70S6K signaling pathway both in vitro and in vivo. Taken together, these findings strongly suggest that a critical role of Ets2 in human ESCC pathogenesis via the inactivation of the mTOR/p70S6K signaling pathway.

• Ets2
• apoptosis
• esophageal squamous cell carcinoma
• mTOR/p70S6K signaling pathway
• proliferation

• 5-Fluorouracil
• Apoptosis
• Esophageal cancer cells
• Proliferation
• β-Carotene

• Duroc
• dermal fibroblast
• dermis
• electron microscope
• heterogeneity

Store-operated calcium entry (SOCE), a major mode of extracellular calcium entry, plays roles in a variety of cell activities. Accumulating evidence indicates that the intracellular calcium ion concentration and calcium signaling are critical for the responses induced by oxidative stress. The present study was designed to investigate the potential effect of SOCE inhibition on H₂O₂-induced apoptosis in endothelial progenitor cells (EPCs), which are the predominant cells involved in endothelial repair. The results showed that H₂O₂-induced EPC apoptosis was reversed by SOCE inhibition induced either using the SOCE antagonist ML-9 or via silencing of stromal interaction molecule 1 (STIM1), a component of SOCE. Furthermore, SOCE inhibition repressed the increases in intracellular reactive oxygen species (ROS) levels and endoplasmic reticulum (ER) stress and ameliorated the mitochondrial dysfunction caused by H₂O₂. Our findings provide evidence that SOCE inhibition exerts a protective effect on EPCs in response to oxidative stress induced by H₂O₂ and may serve as a potential therapeutic strategy against vascular endothelial injury.

• Endothelial progenitor cells
• ML-9
• Oxidative stress
• SOCE
• STIM 1

• AKT1
• AKT2
• oesophageal squamous cell carcinoma
• polymorphism
• risk

• Aged
• Carcinoma, Squamous Cell/diagnosis
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Case-Control Studies
• China
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma
• Female
• Gene Expression
• Gene-Environment Interaction
• Haplotypes
• Humans
• Male
• Middle Aged
• Multifactor Dimensionality Reduction
• Odds Ratio
• Polymorphism, Single Nucleotide
• Proto-Oncogene Proteins c-akt/genetics
• Risk Factors