Development Of Esophageal Cancer Research Articles

Development of a prognostic signature for esophageal cancer based on nine immune related genes

BackgroundFunction of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated.MethodsThis study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA).ResultsWe identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM, STC2, NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group.ConclusionsPrognosis related IRGs were identified and a prognostic signature for esophageal cancer based on nine IRGs was developed.

Long noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis

ABSTRACT Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Comprehensive studies on molecular mechanism of ESCA have been carried out. Though numerous long noncoding RNAs (lncRNAs) was reported to participate in the occurrence and development of ESCA, the potential role of lncRNA potassium calcium-activated channel subfamily M regulatory beta subunit 2 (KCNMB2) antisense RNA 1 (KCNMB2-AS1) in ESCA remains to be discovered. This study intends to investigate the detailed function and molecular mechanism of KCNMB2-AS1 in ESCA. Gene expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell invasion and migration were measured by wound healing assay and Transwell assay. Luciferase reporter assay was adopted to validate the interaction between KCNMB2-AS1 and miR-3194-3p. Western blotting was performed to assess protein levels. We discovered that KCNMB2-AS1 was significantly upregulated in ESCA. KCNMB2-AS1 downregulation suppressed the growth, invasion, migration and stemness of ESCA cells. KCNMB2-AS1 bound with miR-3194-3p, and glycogen phosphorylase L (PYGL) was a direct target of miR-3194-3p. KCNMB2-AS1 upregulated PYGL expression by directly binding with miR-3194-3p. Additionally, PYGL overexpression abolished the inhibitory influence of KCNMB2-AS1 depletion on ESCA cell behaviors. Collectively, lncRNA KCNMB2-AS1 promotes ESCA development through targeting the miR-3194-3p/ PYGL axis, which might provide theoretical basis to explore novel biomarkers for ESCA treatment.

Identification of prognostic hypoxia-related genes signature on the tumor microenvironment in esophageal cancer.

Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer. The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures. We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups. Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.

Clinical significance and prognostic value of Porphyromonas gingivalis infection in lung cancer

A variety of pathogenic microorganisms can promote the occurrence and development of malignant tumors by colonizing in the body. It has been shown that Porphyromonas gingivalis (P. gingivalis) can be colonized for a long time in upper gastrointestinal tumors and is closely related to the occurrence and development of esophageal cancer in previous studies of our team. Because the esophagus and trachea are closely adjacent and P. gingivalis can instantly enter and colonize in cells, we speculate that P. gingivalis may be colonized in lung cancer cells through oral or blood, promoting the malignant progression of lung cancer. In this study, we investigated P. gingivalis infection in lung carcinoma tissues and adjacent lung tissues, and found that the colonization rate of P. gingivalis in carcinoma tissues was significantly higher than that in adjacent lung tissues. Therefore, we propose that the microenvironment of cancer cells is more conducive to the survival of P. gingivalis. Then, we analyzed the correlation between P. gingivalis infection and clinicopathological features and survival prognosis of patients with lung cancer. It was found that P. gingivalis infection was closely related to smoking, drinking, lymph node metastasis and clinical stage. Moreover, the survival rate and median survival time of patients with P. gingivalis infection were significantly shortened. Therefore, we put forward the view that long term smoking and drinking will cause a bad oral environment, increasing the risk of P. gingivalis infection, then P. gingivalis infection will promote the malignant progression of lung cancer.

LncRNA GIHCG Promotes the Development of Esophageal Cancer by Modulating miR-29b-3p/ANO1 Axis.

BackgroundEsophageal cancer is one of the most frequent cancers with a higher mortality worldwide. Although many long non-coding RNAs (LncRNAs) are reported to play important roles in the progression of esophageal cancer, the function of lncRNA GIHCG in esophageal cancer remains unclear.MethodsThe expression of GIHCG in esophageal cancer tissues and cancer cell lines was detected by qRT-PCR. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay, EdU staining assay and colony formation assay. Cell invasion and migration were measured by transwell assay. Cell apoptosis was detected by a flow cytometer. Luciferase reporter assay and RIP assay were used to determine the interaction between GIHCG and miR-29b-3p, and their subsequent regulation of anoctamin 1 (ANO1). The expression of ANO1 in esophageal cancer tissues and cell lines was detected by Western blot. The effect of GIHCG/miR-29b-3p in tumor formation was assessed by the xenograft nude mice model in vivo.ResultsGIHCG was significantly upregulated in esophageal cancer tissues and relevant cancer cell lines. Downregulation of GIHCG significantly inhibited the growth, colony formation, invasion, migration and induced apoptosis of esophageal cancer cells in vitro. Bioinformatic analysis and RIP assay determined that GIHCG was a sponge of miR-29b-3p, and ANO1 was a direct target of miR-29b-3p. Moreover, functional experiments showed that GIHCG upregulated ANO1 expression by directly sponging miR-29b-3p. Furthermore, in vivo experiment revealed that knockdown of GIHCG significantly inhibited tumor growth in nude mice.ConclusionOur study revealed that lncRNA GIHCG promoted the progression of esophageal cancer by targeting the miR-29b-3p/ANO1 axis, suggesting that GIHCG might be a novel therapeutic target for esophageal cancer.

Statins Inhibit Toll-Like Receptor 4–Mediated Growth of Human Esophageal Adenocarcinoma Cells

BackgroundEsophageal adenocarcinoma (EAC) is a lethal malignancy with poor prognosis. Pharmacologic inhibitors of inflammation, such as statins, have been shown to decrease the risk of development and progression of esophageal cancer, but the mechanism of this protection is unclear. The objective of this study was to elucidate the effect of statins on toll-like receptor 4-mediated–proliferation of human EAC cells and identify the mechanism responsible for these observed effects. MethodsHuman EAC cells (OE33 and FLO1) were treated with simvastatin or atorvastatin for increasing doses and time periods. Toll-like receptor 4 (TLR4) expression was assessed. Cells were pretreated with statin followed by lipopolysaccharide (LPS). Cell proliferation and expression of signaling proteins were evaluated. FLO1 cells were injected into the flank of nude mice. Mice received intraperitoneal injections of simvastatin, atorvastatin, or control solution and tumor volume was measured. ResultsOE33 and FLO1 cells demonstrated decreased TLR4 expression after treatment with simvastatin or atorvastatin for 8 h (P < 0.05). LPS increased proliferation, whereas pretreatment with statin abolished this response (P < 0.05). Statins decreased expression and activation of LPS-induced signaling proteins, including MyD88, TRAF6, Akt, and NF-κB (P < 0.05). Mice receiving daily statin injections demonstrated smaller tumors than control mice (P < 0.001 at day 33). ConclusionsTreatment of EAC cells with simvastatin or atorvastatin decreases TLR4-mediated proliferation and in vivo tumor growth. Decreased TLR4 expression and subsequent reduction in MyD88-dependent signaling could be a mechanism by which statins act to reduce tumor growth rates.

Porphyromonas gingivalis promotes tumor progression in esophageal squamous cell carcinoma.

Increasing evidence indicates that the microbiome may influence tumor growth and modulate the tumor microenvironment of gastrointestinal cancers. However, the role of oral bacteria in the development of esophageal squamous cell carcinoma (EsoSCC) has remained unclear. Herein, we investigated the relationship between the periodontal pathogen Porphyromonas gingivalis and EsoSCC. To identify bacterial biomarkers associated with EsoSCC, we analyzed microbiomes in oral biofilms. The presence of P. gingivalis in esophageal tissues and relationships of P. gingivalis infection with clinicopathologic characteristics in 156 patients with EsoSCC were assessed using immunohistochemistry. The role of P. gingivalis infection in in vitro and in vivo EsoSCC progression was also assessed. Microbiota profiles in oral biofilms revealed that P. gingivalis abundance was associated with an increased risk of EsoSCC development. In total, 57% of patients with EsoSCC were found to be infected with P. gingivalis. The presence of P. gingivalis was found to be associated with advanced clinical stages and a poor prognosis. It was also found to be associated with an elevated esophageal cancer incidence in a 4-nitroquinoline 1-oxide-induced mouse model andwith an increased xenograft tumor growth. P. gingivalis infection increased interleukin (IL)-6 production and it promoted epithelial-mesenchymal transition and the recruitment of myeloid-derived suppressor cells. Furthermore, inhibited IL-6 signaling attenuated the tumor-promoting effects of P. gingivalis in 4-nitroquinoline 1-oxide-treated mice and xenograft mouse models. Our data indicate that P. gingivalis may promote esophageal cancer development and progression. Direct targeting of P. gingivalis or concomitant IL-6 signaling may be a promising strategy to prevent and/or treat EsoSCC associated with P. gingivalis infection.

P2Y2 receptor activation promotes esophageal cancer cells proliferation via ERK1/2 pathway

Esophageal cancer is a prominent worldwide illness that is divided into two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Mortality rates are alarming, and the understanding of the mechanisms involved in esophageal cancer development, becomes essential. Purinergic signaling is related to many diseases and among these various types of tumors. Here we studied the effects of the P2Y2 receptor activation in different types of esophageal cancer. Esophageal tissue samples of healthy controls were used for P2Y2R expression quantification. Two human esophageal cancer cell lines Kyse-450 (squamous cell carcinoma) and OE-33 (adenocarcinoma) were used to perform in vitro analysis of cell proliferation, migration, adhesion, and the signaling pathways involved in P2Y2R activation. Data showed that P2Y2R was expressed in biopsies of patients with ESCC and adenocarcinoma, as well as in the two human esophageal cancer cell lines studied. The RT-qPCR analysis demonstrated that OE-33 cells have higher P2RY2 expression than Kyse-450 squamous cell line. Results showed that P2Y2R activation, induced by ATP or UTP, promoted esophageal cancer cells proliferation and colony formation. P2Y2R blockage with the selective antagonist, AR-C 118925XX, led to decreased proliferation, colony formation and adhesion. Treatments with ATP or UTP activated ERK 1/2 pathway in ESCC and ECA cells. The P2Y2R antagonism did not alter the migration of esophageal cancer cells. Interestingly, the esophageal cancer cell lines presented a distinct profile of nucleotide hydrolysis activity. The modulation of P2Y2 receptors may be a promising target for esophageal cancer treatment.

Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism.

BACKGROUNDIt is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) is an important risk factor for the development of esophageal squamous cell carcinoma (ESCC). It remains controversial whether human papillomavirus (HPV) infection contributes to the occurrence/development of ESCC. There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B (ADH1B) and ALDH2 genotypes was evaluated.AIMTo evaluate relationships between HPV infection and development of esophageal cancer, particularly early esophageal cancer, based on ADH1B/ALDH2 polymorphisms.METHODSWe conducted an exploratory retrospective study using new specimens, and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital. Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2. We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe.RESULTSHPV was detected in 15 (10.3%) of the 145 patients with ESCC. HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1 + *2/*2 were 10.8% and 9.8%, respectively (P = 1.00). HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2 + *2/*2 were 12.0% and 10.0%, respectively (P = 0.72). HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1% and 8.7%, respectively (P = 0.68). HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8% and 8.3%, respectively (P = 0.59). The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPV-negative groups were 14.4% and 21.4% (P = 0.22), respectively.CONCLUSIONIn the present situation, HPV status is considered to be less important than other risk factors, such as alcohol consumption, smoking habit, ADH1B/ALDH2 polymorphisms, and HPV status would therefore have no effect on ESCC risk management.

LncRNA TUG1 promotes esophageal cancer development through regulating PLK1 expression by sponging miR-1294.

Esophageal cancer is one of the malignant tumor with poor survival. The 5-year survival rate of esophageal cancer patients remains poor due to limited therapeutic options and the development of drug-resistance. Recent evidence suggests that long non-coding RNAs (lncRNAs) are involved in occurrence and development of tumor, however, the molecular mechanisms of lncRNA taurine-upregulated gene 1 (TUG1) in esophageal cancer remain unknown. TUG1 was overexpressed in esophageal cancer tissues and cells. The knockdown of TUG1 repressed proliferation and invasion, while promoted apoptosis of esophageal cancer cells by negatively regulating miR-1294 expression. Furthermore, PLK1 was a target mRNA of miR-1294 in esophageal cancer cells. Therefore, the effects of PLK1 silencing on proliferation, apoptosis, and invasion of esophageal cancer cells could be overturned by silencing miR-1294. Additionally, TUG1 silencing inhibited growth of tumor cells in vivo. TUG1 was found as oncogenic gene in esophageal cancer. Mechanically, TUG1 attributed to esophageal cancer process by regulating miR-1294/ PLK1 axis.

Circ-PRMT5 stimulates migration in esophageal cancer by binding miR-203.

The study aimed to uncover the role of circ-PRMT5 in triggering the migratory ability of esophageal cancer by regulating microRNA-203 (miR-203) level. Circ-PRMT5 levels in 56 matched esophageal cancer tissues and paracancerous ones were detected. The relationship between circ-PRMT5 level and clinical data of esophageal cancer patients was analyzed. Migratory abilities in TE-1 and OE33 cells influenced by circ-PRMT5 were evaluated by transwell and wound healing assay. Regulatory effect of circ-PRMT5 on miR-203 level, and the involvement of miR-203 in the development of esophageal cancer were determined through Dual-Luciferase reporter assay and rescue experiments. Circ-PRMT5 was upregulated in esophageal cancer tissues and cell lines. The expression level of circ-PRMT5 was positively correlated to the rates of lymphatic metastasis and distant metastasis of esophageal cancer. Knockdown of circ-PRMT5 attenuated migratory abilities in TE-1 and OE33 cells. MiR-203 was verified to be the target gene binding circ-PRMT5, with a negative correlation between each other. Notably, miR-203 was responsible for the regulatory effect of circ-PRMT5 on migratory ability in esophageal cancer. Circ-PRMT5 is positively correlated to the rates of lymphatic metastasis and distant metastasis of esophageal cancer. It promotes migratory ability in esophageal cancer by targeting miR-203.

S2008 A Case of Esophageal Adenocarcinoma in a Young Male With Longstanding Untreated Eosinophilic Esophagitis

INTRODUCTION: Eosinophilic Esophagitis (EoE) has been increasing in incidence over the last decade due to the increasing number of EGD with biopsies preformed. Up to 6.5% patients undergoing EGD for any indication are diagnosed with EoE and 22% in patients for dysphagia. EoE is present in all age groups but peak incidence is bimodal, in first and third decades of life. Here we describe a case of esophageal adenocarcinoma in a patient with history of EoE. CASE DESCRIPTION/METHODS: A 42 year-old male (BMI 27 kg/m2) with PMHx of untreated EoE for 10 years presented to the ED for food bolus impaction a few hours after eating pork. No history of alcohol or tobacco use. Emergent EGD was performed with successful removal of solid food bolus in middle third of the esophagus. There were endoscopic mucosal changes consistent with EoE (EoE-EREFS: Edema 1, Rings 2, Exudates 1, Furrows 1 and Stricture 0) within the entire esophagus and a nodularity appreciated at the GEJ. Biopsies obtained from proximal and distal esophagus showed more than 50 and 100 eosinophils/per HPF respectively. The GEJ lesion showed high grade dysplasia in the settings of goblet cell metaplasia. Repeat EGD 3 weeks later revealed a medium sized fungating and ulcerated mass at the GEJ which was circumferential and partially obstructing. The biopsies showed esophageal adenocarcinoma with indeterminate HER2 oncogene expression, staged as T3N1 based on mini-probe EUS. Oncology classified the patient as cT3N1Mx. The patient received chemo-radiation (5-fluorouracil/oxaliplatin) over 37 days followed by robotic assisted laparoscopic Ivor Lewis esophagogastrectomy with left gastric hepatic artery and celiac lymphadenectomy with successful remission, T0N0. Patient remained in clinical remission at 6 months follow up. DISCUSSION: An estimated 17,500 new cases of esophageal cancer were reported in 2016. Incidence was 4 in 100,000 and increases with age starting from 0.2 in 100,000 at age 30 increasing to 26 in 100,000 at age 80. Mortality was 3.9 in 100,000 deaths and has a 5 year survival of 18.9%. Current risk factors for development of esophageal cancer are alcohol, smoking, and obesity. No clear genetic factors have been associated with development and it is unknown if EoE is a risk factor. However, chronic inflammation and structural changes may be a contributor to malignancy and further research should focus on this area given diseases mortality rates.Figure 1.: A. Food Bolus at Middle Third of the Esophagus B. Abnormal Mucosa at the Gastro-Esophageal Junction C. Gastric Cardia, retroflex view: Mass.Figure 2.: Proximal esophagus shows increased intraepithelial eosinophils, consistent with eosinophilic esophagitis.Figure 3.: GE Junction biopsy shows adenocarcinoma arising in the background of barrett’s esophagus.

M6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1.

N6-methyladenosine (m6A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m6A modification and m6A RNA methylation regulators were involved in cancer progression. However, the m6A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m6A regulators using The Cancer Genome Atlas data and found 14 of 19 m6A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of m6A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m6A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m6A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

Epidemiology of esophageal cancer: update in global trends, etiology and risk factors.

Esophageal cancer is the eighth most common type of cancer worldwide and constitutes the sixth leading cause of cancer deaths. It is characterized by its high mortality rate, poor prognosis at time of diagnosis and variability based on geographic location. Present day, the prevalence of esophageal cancer is in transition. Although esophageal squamous cell carcinoma continues to be the most prevalent type worldwide, esophageal adenocarcinoma is quickly becoming the most prevalent type in developed countries. Risk factors for the development of esophageal squamous cell carcinoma include low socioeconomic status, consumption of tobacco, alcohol, hot beverages, and nitrosamines. Additionally, micronutrient deficiencies have also been linked to the development of esophageal squamous cell cancer. These include vitamin C, vitamin E, and folate. With respect to esophageal adenocarcinoma, risk factors include Barrett's esophagus, gastroesophageal reflux disease, obesity, and tobacco consumption. Screening for esophageal cancer will likely play an essential role in prevention, and consequently, mortality in the future. Present day, there are no established guidelines for esophageal squamous cell cancer screening. Guidelines for esophageal adenocarcinoma are more well established but lack concrete evidence in the form of randomized controlled trials. This review will discuss the epidemiology, risk factors, and current prevention strategies for esophageal cancer in depth. It is our aim to raise awareness on the aforementioned topics to increase public health efforts in eradicating this disease.

Involvement of Fusobacterium Species in Oral Cancer Progression: A Literature Review Including Other Types of Cancer.

Chronic inflammation caused by infections has been suggested to be one of the most important cause of cancers. It has recently been shown that there is correlation between intestinal bacteria and cancer development including metastasis. As over 700 bacterial species exist in an oral cavity, it has been concerning that bacterial infection may cause oral cancer. However, the role of bacteria regarding tumorigenesis of oral cancer remains unclear. Several papers have shown that Fusobacterium species deriving the oral cavities, especially, play a crucial role for the development of colorectal and esophageal cancer. F. nucleatum is a well-known oral bacterium involved in formation of typical dental plaque on human teeth and causing periodontal diseases. The greatest characteristic of F. nucleatum is its ability to adhere to various bacteria and host cells. Interestingly, F. nucleatum is frequently detected in oral cancer tissues. Moreover, detection of F. nucleatum is correlated with the clinical stage of oral cancer. Although the detailed mechanism is still unclear, Fusobacterium species have been suggested to be associated with cell adhesion, tumorigenesis, epithelial-to-mesenchymal transition, inflammasomes, cell cycle, etc. in oral cancer. In this review, we introduce the reports focused on the association of Fusobacterium species with cancer development and progression including oral, esophageal, and colon cancers.

MicroRNA-140 Represses Esophageal Cancer Progression via Targeting ZEB2 to Regulate Wnt/β-Catenin Pathway

BackgroundMicroRNAs have been reported to play regulatory functions in various cancers, including esophageal cancer. The aim of this study was to investigate the effects of miR-140 on the progression of esophageal cancer and the underlying regulatory mechanism. MethodsThe levels of miR-140 and zinc finger E-box-binding homeobox 2 (ZEB2) messenger RNA in esophageal cancer tissues and cell lines were measured by quantitative real-time polymerase chain reaction. The protein levels of ZEB2, β-catenin, c-Myc, and cyclinD1 were determined by Western blot. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, the relationship between miR-140 and ZEB2 was predicted by TargetScan online database and confirmed by dual-luciferase reporter assay. The tumor xenograft model was used to verify the role of miR-140 in esophageal cancer progression in vivo. ResultsThe expression of miR-140 was downregulated whereas ZEB2 expression was upregulated in esophageal cancer tissues compared with paracancerous normal tissues. Functionally, both miR-140 overexpression and ZEB2 knockdown inhibited proliferation, migration, and invasion and induced apoptosis in esophageal cancer cells. ZEB2 overexpression reversed the effects of miR-140 on proliferation, apoptosis, migration, and invasion of esophageal cancer cells. Mechanistically, ZEB2 was identified as a target of miR-140. Furthermore, miR-140 suppressed Wnt/β-catenin pathway by regulating ZEB2 expression in esophageal cancer cells. MiR-140 inhibited tumor growth of esophageal cancer through repressing ZEB2 expression in vivo. ConclusionsOur results demonstrated that miR-140 inhibited esophageal cancer development by targeting ZEB2 through inactivating Wnt/β-catenin pathway.

Cadmium inhibits apoptosis of human esophageal epithelial cells by upregulating CDK6

Cadmium (Cd) exposure in environment is associated with development of esophageal cancer. However, the mechanisms of Cd-induced carcinogenesis are still not been fully cleared, and the present study aimed to explore the possible etiological mechanism of Cd-induced esophageal cancer. Human esophageal epithelial cell lines (HET-1A and KYSE450) were treated with CdCl2 at 0.05 mg/l for 12, 24 h, and the then the apoptosis were detected using flow cytometry with annexin-V-FITC/PI staining. Results showed that apoptosis of treatment groups was significantly inhibited, and decreased reactive oxygen species (ROS) production played a key role in the inhibitory effects by upregulating Bcl-2 and downregulating Caspase-3/9. The relief of oxidative stress during Cd exposure was actively promoted by the increased nicotinamide adenine dinucleotide phosphoric acid and glutathione levels. To investigate the causes of enhanced intracellular antioxidant capacity, the activity of pyruvate kinase (PK), a key enzyme of glycolysis, was detected. Our results showed that PK activity was inhibited, suggesting that glycolysis process was blocked which promoted more intermediate metabolites of glycolysis to be used for reduced nicotinamide adenine dinucleotide phosphoric acid (NADPH) or other antioxidants synthesis. PK activity was closely correlated with phosphorylation of pyruvate kinase M2 (PKM2), and a highly negative correlation (correlation coefficients: −0.835, p < 0.05) between them was found. Western blotting showed the overphosphorylation of PKM2 in Cd-exposed cells, resulting from increased expression of cyclin-dependent kinases 6 (CDK6). These results suggested a possible mechanism of carcinogenic: Cd-induced upregulation of CDK6 in esophageal cell lines caused PKM2 overphosphorylation inhibiting PK activity, thereby shunting glucose-derived carbon into the pentose phosphate pathway and promoting the production of NADPH and reduced glutathione (GSH) to neutralize ROS, which finally results in the inhibited apoptosis.

A Literature Review on the Role of TBX5 in Expression and Progression of Lung Cancer: Current Perspectives

T-box转录因子（T-box transcription factor gene, TBX）基因涉及器官的发生，TBX5在人的正常心脏和肺组织中表达水平最高。TBX5的缺乏可能导致胸廓发育畸形和膈肌发育异常，其异位表达和过表达会诱导细胞凋亡和抑制细胞生长。既往研究发现了TBX5在食管腺癌、胃癌、结肠癌和乳腺癌的发生和发展中的潜在作用。我们对TBX2亚家族的基因表达和预后之间的关系进行了综述，同时探究TBX5在调控肺癌发生发展机制中的研究进展。虽然TBX5和肺癌发生之间的关系尚不明确，不过TBX5可以显著抑制人体内肿瘤生长，其表达水平和肺癌的进展呈现负相关。由此，TBX5的基因表达水平和甲基化程度是潜在的表证肺癌增殖和转移的生物标志物，具有作为肺癌治疗靶点的潜力。

LncRNA EIF3J-AS1 enhanced esophageal cancer invasion via regulating AKT1 expression through sponging miR-373-3p

Esophageal cancer (ECa) remains a major cause of mortality across the globe. The expression of EIF3J-AS1 is altered in a plethora of tumors, but its role in ECa development and progression are undefined. Here, we show that EIF3J-AS1 is up-regulated in ECa and that its expression correlates with advanced TNM stage (P = 0.014), invasion depth (P = 0.001), positive lymph node metastasis (P < 0.001) and poor survival (OS: P = 0.0059; DFS: P = 0.0037) in ECa. Functional experiments showed that knockdown EIF3J-AS1 inhibited ECa growth and metastasis through in vitro and in vivo experiments. Regarding the mechanism, EIF3J-AS1/miR-373-3p/AKT1 established the ceRNA network involved in the modulation of cell progression of ECa cells. Overall, EIF3J-AS1 may exhibit an oncogenic function in ECa via acting as a sponge for miR-373-3p to up-regulate AKT1 mRNA level, and may serve as a potential therapeutic target and a prognostic biomarker for ECa patients.

Investigation of IL-4, IL-10, and HVEM polymorphisms with esophageal squamous cell carcinoma: a case-control study involving 1929 participants.

It is believed that an individual’s hereditary factors may be involved in the development of esophageal cancer (EC). The present study recruited 721 esophageal squamous cell carcinoma (ESCC) cases and 1208 controls and explored the roles of single nucleotide polymorphisms (SNPs) in the interleukin-4 (IL-4), IL-10, and herpesvirus entry mediator (HVEM) genes in contributing to ESCC risk. IL-4, IL-10, and HVEM SNPs were analyzed by employing an SNPscan method. After adjustment for body mass index (BMI), smoking, drinking, age and gender, we identified that the rs2070874 T>C locus in IL-4 gene decreased the risk of ESCC (CC vs. TT: P=0.008; CC vs. TT/TC: P=0.010). After a stratified analysis, we suggested that the IL-4 rs2070874 T>C variants might be a protective factor for ESCC in male, ≥63 years old, never smoking, drinking and BMI < 24 kg/m2 subgroups. In addition, we identified that the rs2243263 G>C polymorphism in IL-4 gene was a risk factor for ESCC development in the BMI ≥ 24 kg/m2 subgroup (GC vs. GG: P=0.030 and GC/CC vs. GG: P=0.018). We identified an association of the IL-4 rs2070874 T>C SNP with the decreased susceptibility of ESCC in stage I/II subgroup. Finally, we found an association of the IL-10 rs1800872 T>G SNP with a worse differentiation (TG vs. TT: P=0.048 and GG/TG vs. TT: P=0.032). In conclusion, the findings indicate a potential importance of IL-4 rs2070874 T>C, IL-4 rs2243263 G>C and IL-10 rs1800872 T>G SNPs in the development of ESCC.