Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive tract that poses a significant threat to human health, with an incidence rate that continues to rise globally. Increasing research highlights the crucial role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating ferroptosis and contributing to the malignant progression of ESCC. These ncRNAs influence the proliferation, apoptosis, and invasion capabilities of ESCC cells by modulating iron metabolism and redox balance. miRNAs can regulate cellular iron accumulation and oxidative stress by targeting ferroptosis-related genes; lncRNAs may indirectly affect iron metabolic pathways by competitively binding to miRNAs; circRNAs, through a sponge effect, may regulate the activity of miRNAs. This review systematically summarizes the mechanisms of ncRNAs-mediated regulation of ferroptosis in ESCC, focusing on molecular mechanisms, regulatory networks, and their specific roles in the ferroptosis process. Additionally, the potential of ncRNAs in ESCC diagnosis, prognosis assessment, and therapeutic intervention is discussed, aiming to provide new insights and targets for ferroptosis-based tumor therapy.
Ferroptosis/genetics* ; Humans ; Esophageal Neoplasms/physiopathology* ; Esophageal Squamous Cell Carcinoma ; MicroRNAs/physiology* ; RNA, Long Noncoding/physiology* ; RNA, Circular ; RNA, Untranslated/physiology*

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

OBJECTIVETo investigate the relationship between plasma miR-93-5p and the risk of esophageal cancer, as well as the influence of miR-93-5p on the biological function of esophageal cancer cells, exerted through exosomes.

METHODSThe expression of plasma miR-93-5p in esophageal cancer patients and healthy controls was analysed by real-time quantitative PCR. The influence of miR-93-5p on the risk and prognosis of esophageal carcinoma was analyzed by conditional logistic regression and survival analysis. The effect of miR-93-5p on the biological function of recipient cells was investigated by establishing an in vitro donor cell co-culture model. The target gene of miR-93-5p was validated by luciferase reporter assay and Western Blotting.

RESULTSUpregulation of plasma miR-93-5p expression significantly increases the risk of esophageal cancer and is associated with poor prognosis. miR-93-5p transferred by exosomes promotes the proliferation of recipient esophageal cancer cells and affects the expression of PTEN and its downstream proteins p21 and cyclin D1.

CONCLUSIONOur study provides a reference for the identification of biomarkers for the diagnosis and prognosis of esophageal cancer.

Aged ; Cell Communication ; China ; Esophageal Neoplasms ; physiopathology ; Exosomes ; physiology ; Female ; Humans ; Male ; MicroRNAs ; metabolism ; Middle Aged ; PTEN Phosphohydrolase ; genetics ; metabolism ; Risk

OBJECTIVETo explore the application of mesoesophagus suspension technique to improve the upper mediastinal lymph node dissection during thoracoscopic esophagectomy in the treatment of esophageal cancer.

METHODSClinical data of 164 thoracic esophageal cancer patients who underwent combined thoracoscopic and laparoscopic esophagectomy with two-field lymph node dissection in the Union Hospital of Fujian Medical University between October 2012 and June 2015 were retrospectively analyzed. Among 164 patients, 80 cases underwent upper mediastinal lymph node dissection by traditional method (traditional group), and the remaining 84 cases underwent upper mediastinal lymph node dissection by mesoesophagus suspension technique (suspension group). The operation time, estimated blood loss, number of excised lymph nodes and postoperative complications were compared between the two groups.

RESULTSThere were no significant differences in gender, age, location of tumor and pathology stage between the two groups. The operation time in the two groups was similar. The suspension group had significantly less thoracic blood loss than traditional group [(85±5) ml vs.(140±7) ml, P=0.000]. The number of dissected lymph nodes of bilateral recurrent laryngeal nerve was more in suspension group [median (interquartile range): left: 3 (2 to 4) vs. 2 (1 to 3), P=0.013; right: 3(2 to 6) vs. 2(1 to 3), P=0.007]. There was no significant difference in metastatic rate of lymph node in different sites between the two groups. The highest metastatic rate of suspension and traditional group was found at paracardia lymph nodes[22.6%(19/84) and 22.5%(18/80)], the next was at right laryngeal nerve lymph nodes [17.9%(15/84) and 15.0%(12/80)] and left laryngeal nerve lymph nodes [16.7%(14/84) and 12.5%(10/80)]. There were no significant differences with regard to the incidence of major postoperative complications between two groups, including respiratory complication, anastomotic leakage, vocal cord palsy.

CONCLUSIONSUpper mediastinal bilateral recurrent laryngeal nerve lymph node is the predilection site of lymphatic metastasis of thoracic esophageal cancer. Application of mesoesophagus suspension technique in thoracoscopic esophagectomy can improve the clearance quality of bilateral recurrent laryngeal nerve lymph nodes.

Anastomotic Leak ; Blood Loss, Surgical ; Esophageal Neoplasms ; surgery ; Esophagectomy ; adverse effects ; methods ; Female ; Humans ; Laparoscopy ; Lymph Node Excision ; adverse effects ; methods ; Lymph Nodes ; anatomy & histology ; pathology ; surgery ; Lymphatic Metastasis ; physiopathology ; Male ; Mediastinum ; surgery ; Operative Time ; Postoperative Complications ; Recurrent Laryngeal Nerve ; physiopathology ; Retrospective Studies ; Treatment Outcome

To investigate the effect of RAD18-siRNA on cell proliferation and chemotherapy sensitivity of esophageal squamous cell carcinoma (ESCC) ECA-109 cells.RAD18-siRNA was transfected into human ECA-109 cells by Lipofectamine 3000. Quantitative PCR and Western blot were performed to detect RAD18 and CyclinD1 expression; CCK-8 assay was used to determine cell proliferation and chemotherapy drug sensitivity; flow cytometry was used to determine cell cycle. Correlation between RAD18 and CyclinD1 mRNA expression was analyzed by Pearson's correlation.Compared with non-transfected cells, the expression of RAD18 in RAD18-siRNA group was significantly decreased (<0.05). The cell proliferation was inhibited (<0.05) and the cell number of G1 phase was increased, G2/M phase cells decreased (<0.05) in RAD18-siRNA group. After treatment with different concentrations of cisplatin or 5-FU, the survival rate of the two cell groups was reduced (all<0.05), and the IC50 of RAD18-siRNA group was significantly lower than that of non-transfected group (<0.05). The mRNA expression of RAD18 was positively correlated with CyclinD1 expression in ESCC tissues(=0.478,<0.01).Down-regulated expression of RAD18 can decrease the cell proliferation and increase chemo-sensitivity of ESCC cells, and CyclinD1 may participate in the process.
Adjuvants, Pharmaceutic ; pharmacology ; Carcinoma, Squamous Cell ; drug therapy ; physiopathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Cyclin D1 ; drug effects ; genetics ; DNA-Binding Proteins ; administration & dosage ; pharmacology ; Down-Regulation ; drug effects ; genetics ; Drug Resistance, Neoplasm ; drug effects ; Drug Screening Assays, Antitumor ; methods ; Drug Synergism ; Esophageal Neoplasms ; drug therapy ; physiopathology ; Fluorouracil ; pharmacology ; G1 Phase ; drug effects ; G2 Phase ; drug effects ; Humans ; Metaphase ; drug effects ; RNA, Small Interfering ; administration & dosage ; pharmacology ; Transfection ; Ubiquitin-Protein Ligases ; administration & dosage ; pharmacology

INTRODUCTIONLarge, recent population-based data for evaluating the predictors of oesophageal variceal bleeding (OVB) among cirrhotic patients is still lacking. This study aimed to determine the cumulative incidence of OVB among cirrhotic patients and identify the predictors of OVB occurrence.

METHODSPatient information on 38,172 cirrhotic patients without a history of OVB, who were discharged between 1 January 2007 and 31 December 2007, was obtained from the Taiwan National Health Insurance Database for this study. All patients were followed up for three years. Death was the competing risk when calculating the cumulative incidences and hazard ratios (HRs) of OVB.

RESULTSOVB was present in 2,609 patients (OVB group) and absent in 35,563 patients (non-OVB group) at hospitalisation. During the three-year follow-up period, the cumulative incidence of OVB was 44.5% and 11.3% in the OVB and non-OVB group, respectively (p < 0.001). Modified Cox regression analysis showed that the HR of OVB history was 4.42 for OVB occurrence (95% confidence interval [CI] 4.13-4.74). Other predictors for OVB occurrence included hepatocellular carcinoma (HR 1.16, 95% CI 1.09-1.24), young age (HR 0.98, 95% CI 0.98-0.98), ascites (HR 1.46, 95% CI 1.37-1.56), alcohol-related disorders (HR 1.20, 95% CI 1.12-1.28), peptic ulcer bleeding (HR 1.26, 95% CI 1.13-1.41) and diabetes mellitus (HR 1.14, 95% CI 1.06-1.23).

CONCLUSIONCirrhotic patients have a fourfold increased risk of future OVB following the first incidence of OVB.

Adult ; Aged ; Alcoholism ; complications ; Ascites ; complications ; Carcinoma, Hepatocellular ; complications ; Databases, Factual ; Diabetes Complications ; Esophageal and Gastric Varices ; epidemiology ; etiology ; Female ; Gastrointestinal Hemorrhage ; epidemiology ; etiology ; Humans ; Incidence ; Liver Cirrhosis ; complications ; physiopathology ; Liver Neoplasms ; complications ; Male ; Middle Aged ; Peptic Ulcer ; complications ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Risk ; Taiwan

No abstract available.
Adenocarcinoma/*complications/diagnosis ; Aged ; Esophageal Achalasia/diagnosis/*etiology/physiopathology ; Esophageal Sphincter, Upper/physiopathology ; Humans ; Lung Neoplasms/*complications/diagnosis ; Male ; Neoplasm Staging ; Predictive Value of Tests ; Risk Factors ; Tomography, X-Ray Computed

OBJECTIVETo explore the role of S100A4 in the epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma and its possible molecular mechanism.

METHODSThree chemically synthesized S100A4 siRNA sequences were transiently transfected into esophageal carcinoma EC9706 cells. EC9706 cells transfected with negative siRNA, lipofectamine 2000, and vacant EC9706 cells were used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the inhibition rate of S100A4 siRNA. S100A4 siRNA2 with the best inhibition rate was chosen to transiently transfect into EC9706 cells under the same conditions. The EC9706 cells transfected with negative siRNA, lipofectamine 2000 and vacant EC9706 cells were also used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the mRNA and protein expressions of E-cadherin, vimentin and snail. The morphology of EC9706 cells was observed under an inverted microscope. Boyden chamber and scratch test were used to detect the invasion and migration ability of EC9706 cells, and CCK8 assay was used to detect the proliferation ability of EC9706 cells. EC9706 cells transfected with S100A4 siRNA2 were further transfected with snail eukaryotic expression vector. The EC9706 cells transfected with S100A4 siRNA, EC9706 cells transfected with snail eukaryotic expression vector and vacant EC9706 cells were used as control. The above indexes of all the groups were observed, too.

RESULTSThe S100A4 mRNA and protein expression levels of the S100A4 siRNA2 group were 0.417 ± 0.041 and 0.337 ± 0.039, the transmembrane cell number was 61.608 ± 8.937, the scratch healing distance was (0.216 ± 0.064) mm, the A value was 0.623 ± 0.084, the E-cadherin mRNA and protein levels were 0.619 ± 0.032 and 0.495 ± 0.034, the vimentin mRNA and protein levels were 0.514 ± 0.032 and 0.427 ± 0.028, the snail mRNA and protein levels were 0.573 ± 0.029 and 0.429 ± 0.041. These data were significantly different with the liposome group, the negative control group and the blank group (P < 0.05 for all). After the S100A4 siRNA2 treatment for 24 h, the appearance of EC9706 cells changed to epithelial cell morphology. The transmembrane cell number and the scratch healing distance of the S100A4 siRNA2+snail eukaryotic expression vector group were (69.382 ± 9.666) cells and (0.274 ± 0.029) mm, the A value was 0.823 ± 0.101, the snail mRNA and protein levels were 0.704 ± 0.037 and 0.625 ± 0.031, the vimentin mRNA and protein levels were 0.712 ± 0.046 and 0.609 ± 0.038, and these data were significantly higher than those of the Sl00A4 siRNA2 group (P < 0.05 for all). The E-cadherin mRNA and protein levels of the S100A4 siRNA2+eukaryotic expression vector group were 0.437 ± 0.038 and 0.381 ± 0.031, significantly lower than those of the S100A4 siRNA2 group (P < 0.05 for all). However, snail had no effect on the morphology of EC9706 cells.

CONCLUSIONSS100A4 may be involved in the EMT process of esophageal squamous-cell carcinoma by regulating the expression of snail and then plays a role in the invasion and metastasis of esophageal carcinoma.

Cadherins ; analysis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; physiopathology ; Cell Line, Tumor ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Esophageal Neoplasms ; metabolism ; pathology ; physiopathology ; Humans ; Indicators and Reagents ; Lipids ; RNA, Messenger ; analysis ; RNA, Small Interfering ; analysis ; physiology ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; antagonists & inhibitors ; genetics ; physiology ; Snail Family Transcription Factors ; Transcription Factors ; analysis ; genetics ; Transfection ; Vimentin ; analysis ; genetics

Marsdenia tenacissima extract (MTE, trade name: Xiao-Ai-Ping injection) is an extract of a single Chinese plant medicine. It has been used for the treatment of cancer in China for decades, especially for esophageal cancer and other cancers in the digestive tract. In the present study, the potential mechanism for MTE's activity in esophageal cancer was explored. The effects of MTE on the proliferation of human esophageal cancer cells (KYSE150 and Eca-109) were investigated by the MTT assay, the BrdU (bromodeoxyuridine) incorporation immunofluorescence assay, and flow cytometric analysis. MTE inhibited cell proliferation through inducing G0/G1 cell cycle arrest in KYSE150 and Eca-109. Western blot analysis was employed to determine protein levels in the MTE treated cells. Compared with the control cells, the expression levels of the cell cycle regulatory proteins cyclin D1/D2/D3, cyclin E1, CDK2/4/6 (CDK: cyclin dependent kinase), and p-Rb were decreased significantly in the cells treated with MTE at 40 mg·mL(-1). In addition, MTE had an inhibitory effect on the MAPK (mitogen-activated protein kinase) signal transduction pathway, including ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38MAPK. Moreover, MTE showed little additional effects on the regulation of cyclin D1/D3, CDK4/6, and p-Rb when the ERK pathway was already inhibited by the specific ERK inhibitor U0126. In conclusion, these data suggest that MTE inhibits human esophageal cancer cell proliferation through regulation of cell cycle regulatory proteins and the MAPK signaling pathways, which is probably mediated by the inhibition of ERK activation.
Apoptosis ; drug effects ; Carcinoma ; drug therapy ; enzymology ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Esophageal Neoplasms ; drug therapy ; enzymology ; physiopathology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; G1 Phase Cell Cycle Checkpoints ; drug effects ; Humans ; MAP Kinase Signaling System ; drug effects ; Marsdenia ; chemistry

OBJECTIVETo study the influence of preoperative chemoradiotherapy (CRT) on pulmonary function and postoperative pulmonary complications in esophageal cancer patients.

METHODSPulmonary function and postoperative pulmonary complications of 63 esophageal cancer patients undergoing preoperative CRT and operation in Cancer Center of Sun Yat-sen University between 2002 and 2013 were collected retrospectively. The influence of preoperative CRT on pulmonary functional indexes and postoperative pulmonary complications were analyzed.

RESULTSAfter preoperative CRT, DLco% decreased significantly (83.7±17.7 vs. 96.4±17.8, P<0.01), while no obvious changes in other indexes were found. Postoperative pulmonary complication rate was 34.9% (22/63), including 19 cases of pneumonia and 3 cases of acute pulmonary injury/acute respiratory distress syndrome. Differences in postoperative pulmonary complication rates were not statistically significant between patients with DLco% <80 and those with DLco% ≥80 patients (29.7% vs. 41.7%, P>0.05), and between patients with DLco% decline ≥15% and those with DLco% decline <15% patients (31.6% vs. 37.8%, P>0.05).

CONCLUSIONPreoperative CRT can damage the diffusion function but not ventilation function of esophageal cancer patients, and does not increase the postoperative pulmonary complication rate.

Chemoradiotherapy ; Esophageal Neoplasms ; drug therapy ; physiopathology ; radiotherapy ; Female ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Perioperative Care ; Postoperative Complications ; prevention & control ; Retrospective Studies