Pathogenesis Of Esophageal Cancer Research Articles

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights.

Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin's influence on EC. This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects. Key focus areas include its impact on insulin signaling, AMP-activated protein kinase (AMPK) activation, and the mTOR pathway, which collectively contribute to its role in mitigating esophageal cancer progression. This review critically examines the body of clinical and preclinical evidence surrounding the potential role of metformin, a widely prescribed anti-diabetic medication, in EC management. Our examination extends to the modulation of inflammation, oxidative stress and angiogenesis, revealing metformin's potential as a metabolic intervention in esophageal cancer pathogenesis. By consolidating epidemiological and clinical data, we assess the evidence that supports metformin's candidacy as an adjuvant therapy for esophageal cancer. By summarizing clinical and preclinical findings, our review aims to enhance our understanding of metformin's role in EC management, potentially improving patient care and outcomes.

M6A regulator-mediated methylation modification patterns and tumor microenvironment immune infiltration with prognostic analysis in esophageal cancer

Esophageal cancer is a highly malignant disease with poor prognosis. Despite recent advances in the study of esophageal cancer, there has been only limited improvement in the treatment and prognosis. N6-methyladenosine (m6A), a type of RNA modification, has been extensively investigated and is involved in many biological behaviors, including tumorigenesis and progression. Thus, more research on m6A modification may increase our understanding of esophageal cancer pathogenesis and provide potential targets. In our study, we integrated the public data of esophageal cancer from The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus (GEO) databases. Unsupervised clustering analysis was used to classify patients into different groups. Gene set variation analysis (GSVA) was performed in a nonparametric and unsupervised mode. We evaluated immune cell infiltration by single sample gene set enrichment analysis (ssGSEA). Differentially expressed genes (DEGs) among m6A clusters were identified using Empirical Bayesian approach. Both multivariate and univariate Cox regression models were used for prognostic analysis. We provided an overview of gene variation and expression of 23 m6A regulators in esophageal cancer, as well as their effects on survival. Based on the overall expression level of m6A regulators, patients were classified into three m6A clusters (A-C) with different immune cell infiltration abundance, gene expression signatures and prognosis. Among m6A clusters, we identified 206 DEGs, according to which patients were classified into 4 gene clusters (A-D). Quantitative m6A score was calculated for each patient based on those DEGs with significant impact on survival. The infiltration of all types of immune cells except type 2 T helper (Th2) cells were negatively correlated with m6A score. M6Acluster C exhibited the lowest m6A score, the most abundant immune cell infiltration, and the worst prognosis, suggesting an immune excluded phenotype. Consistently, gene cluster D with the lowest m6A score showed the worst prognosis. In short, patients with esophageal cancer showed different m6A modification patterns. Quantitative scoring indicated that patients with the lowest m6A score exhibited the most abundant immune cell infiltration and the poorest prognosis. This m6A scoring system is promising to assess m6A modification pattern, characterize immune infiltration and guide personalized treatment and prognostic prediction.

Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis.

Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. Various factors, including dietary habits, and antacid and antibiotic use, have been shown to influence the esophageal microbiome. Conversely, enrichment and diversity of the esophageal microbiome can also impact its function. Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. Additionally, distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy, indicating the role of the esophageal microbiome in modulating treatment outcomes. In this review, we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases, with a focus on identifying microbial communities associated with EC pathogenesis and prognosis. Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients.

Roles of Nuclear Receptors in Esophageal Cancer.

Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs), Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes or tumor suppressors in EC progression. NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC. This review summarizes the studies on NRs in EC in recent years, mainly including in vitro cell experiments and in vivo animal experiments. NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC. The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases.

Genetic alteration and ctDNA mutation profiling of esophageal cancer in Chinese patients.

e16046 Background: Esophageal cancer is the sixth most common cause of cancer-related mortality. There are two distinct histological types of esophageal cancer: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). In China, ESCC is the major subtype. Higher incidence of EAC is observed in western countries. Liquid biopsy detecting circulating tumor DNA is a non-invasive, real-time and highly sensitive approach that is able to identify and monitor the genetic mutations in tumor. Methods: In this study, we collected 490 Chinese esophageal cancer patients from 2018-2022 and characterized the mutational landscape of esophageal tumor tissue and circulating tumor DNA by whole exome sequencing or deep sequencing of targeted gene panel. The consistency of genetic alteration between tumor and ctDNA was also explored. Results: A total of 176 patients with plasma and 345 patients with cancer tissue were analyzed, among them, 31 patients had both ctDNA and tissue biopsy data. 277 genes with 1257 mutations were identified from plasma samples of 176 patients. The top frequently mutated genes were TP53 (89.1%), KMT2D (24.0%), SYNE1 (14.9%), NOTCH1 (14.3%), EP300 (13.7%), LRP1B (13.7%) and ZNF750 (10.3%). The mutation rates of these genes between ctDNA and tissue biopsy (N = 31 patients) were in concordance by Fisher's exact test (P > 0.05). Most frequent mutations were found in TP53 gene, which account for 89.1% of total plasma samples and 90.4% of tumor tissues. KMT2D gene mutations were detected in 24% of patients which encode histone methyltransferase that methylates the Lys-4 position of histone H3 and regulates transcriptional activation, indicating epigenetic regulation might be involved in the pathogenesis of esophageal cancer. Functional enrichment analysis was performed including Gene Ontology (GO) and KEGG analysis across all the three domains, Biological process, Molecular Function, and Cellular component. The KEGG terms with the highest enrichment score were PI3K−Akt signaling pathway, which is a key driver in carcinogenesis. In addition, we didn’t observe the mutually exclusive mutation or co-occurrence pattern of any gene pairs in our cohort. Conclusions: We demonstrated the utility of liquid biopsy to draw a ctDNA mutation profiling of esophageal cancer in Chinese patients. Genetic mutations identified from ctDNA showed consistency with mutations from tumor tissue.

Epidemiological evidence and association of human papillomavirus with esophageal cancer in northeastern Thailand: a case-control study.

Recently, epidemiological evidence of high-risk human papillomavirus (hrHPV) and its association with the increasing risk of esophageal cancer (EC) have been described. However, the involvement of such a virus in the pathogenesis of EC is still inconclusive in the literature. Therefore, our objective was to clarify the epidemiology of HPV infections in primarily diagnosed EC cases and validate this correlation with hospital-based control patients using a retrospective study with a case-control model. Here, we reported that the overall prevalence of HPV DNA was statistically associated with an increased risk of EC (OR, 3.3; 95% CI, 2.5-4.3). Interestingly, a history of gastroesophageal reflux disease (GERD) was constituted and significantly associated with HPV prevalence (adjusted OR, 4.6; 95% CI, 2.2-9.5). Furthermore, our meta-analysis in public databases also indicated that the combined OR and 95% CI between HPV infection and EC risk were 3.31 and 2.53-4.34, respectively, with significant heterogeneity (I2 = 78%). Variations in the geographic study, tissue type, and detection method remain potential predictors of heterogeneity. In addition, publication bias and sensitivity analysis were not observed, and the results exhibited stable outcomes. Collectively, we specify the recent epidemiological evidence in a validation of the distributed HPV, which might be statistically associated with an increased risk of EC. However, additional high-quality studies with larger sample sizes are needed to further verify the link between HPV and EC.

Immune characteristics and genetic markers of esophageal cancer by single-cell analysis: implications for immunotherapy.

Esophageal cancer (EC) is one of the most common cancers worldwide. The prognoses for patients with the same stage of EC can vary substantially. The progress of single-cell analysis technology has furthered the understanding of tumor heterogeneity. This paper aimed to apply single-cell analysis to explore the characteristics of the tumor environment of EC and provide a basis for personalized treatment. The latest gene expression data and clinical follow-up information of single-cell sequencing results of EC samples were downloaded from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) Application Programming Interface (API). A differential gene function analysis of the immune infiltration signature agents in the tumor microenvironment (TME) was performed using bioinformatics analytical methods, and potential molecular targets were sought. We identified specific cell subsets in the EC and paracancerous samples, including panel cells, natural killer (NK) cells, exhausted cluster of differentiation (CD)8+ T cells, CD8+ memory T (Tcm) cells, and effector memory T (Tem) cells, including B cell enrichment in the cancer samples. Differences were detected between B cells and monocytes in stage II and III tumors, which may be related to RNA transcription and degradation. The CXCL8 protein was identified as a valid potential prognostic marker. Cell groups with homogenous cell surface markers exhibit intercellular variations that exert a considerable effect on cell function. Our study will contribute to the understanding of the TME and cellular heterogeneity in EC patients and serve as a valuable resource for in-depth exploration of the pathogenesis of EC and the identification of potential therapeutic targets in the future.

Formononetin, an Active Component of Astragalus Membranaceus, Inhibits the Pathogenesis and Progression of Esophageal Cancer Through the COX-2/Cyclin D1 Axis.

The goal was to investigate the inhibitory effect of formononetin, an active component in Astragalus membranaceus, on the pathogenesis and development of esophageal cancer and the mechanism of action. The expression of COX-2 in cancer tissue and paracancerous tissue of patients with esophageal cancer detected early. C57BL/6 mice were used to construct a 4-nitroquinoline 1-oxide (4-NQO)-induced esophageal cancer model to verify the inhibitory effect of formononetin on the pathogenesis of esophageal cancer. Additionally, human esophageal cancer cells were treated with formononetin, and the effects on the proliferation and cell cycle of esophageal cancer cells were assessed by the CCK-8 assay and flow cytometry. Changes in the expression levels of cyclin D1 and COX-2 mRNA in cells were detected by RT-qPCR and western blot (WB) analysis. The expression level of COX-2 mRNA in esophageal cancer tissue was significantly higher than that in paracancerous tissue. In the mouse cancer model, the incidence of esophageal cancer in mice in the formononetin treatment group was significantly reduced at week 18 (0/15 vs. 2/15) and at week 24 (6/15 vs. 13/15) (all p < 0.05). Formononetin significantly inhibited the proliferation ability of KYSE170 and KYSE150 cells and inhibited the protein expression of COX-2 and cyclin D1 (both p < 0.05). Formononetin, an active component of Astragalus membranaceus, can prevent the pathogenesis and progression of esophageal cancer by reducing the expression of the inflammatory proteins COX-2 and cyclin D1.

Three Major Gastrointestinal Cancers Could Be Distinguished through Subclass-Specific IgG Glycosylation.

Esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC) are three major digestive tract tumors with higher morbidity and mortality due to significant molecular heterogeneity. Altered IgG glycosylation has been observed in inflammatory activities and disease progression, and the IgG glycome profile could be used for disease stratification. However, IgG N-glycome profiles in these three cancers have not been systematically investigated. Herein, subclass-specific IgG glycosylation in CRC, GC, and EC was comprehensively characterized by liquid chromatography-tandem mass spectrometry. It was found that IgG1 sialylation was decreased in all three cancers, and the alterations in CRC and EC may be subclass-specific. IgG4 mono-galactosylation was increased in all three cancers, which was a subclass-specific change in all of them. Additionally, glycopeptides of IgG1-H5N5, IgG2-H4N3F1, and IgG4-H4N4F1 could distinguish all three cancer groups from controls with fair diagnostic performance. Furthermore, bioinformatics verified the differential expression of relevant glycosyltransferase genes in cancer progression. Significantly, those three gastrointestinal cancers could be distinguished from each other using subclass-specific IgG glycans. These findings demonstrated the spatial and temporal diversity of IgG N-glycome among digestive cancers, increasing our understanding of the molecular mechanisms of EC, GC, and CRC pathogenesis.

The Role of m6A Modification and m6A Regulators in Esophageal Cancer.

Simple SummaryN6-methyladenosine (m6A) modification and m6A regulators play important roles in the occurrence and development of various cancers. Esophageal cancer (ESCA), one of the most common gastrointestinal tumors, seriously affects people’s health. In this review article, we summarized the role and possible mechanism of m6A modification and m6A regulators in the occurrence, progression, remedy and prognosis of ESCA, which might be useful for determining the pathogenesis of ESCA and providing direction for the future research of ESCA.N6-methyladenosine (m6A) modification, the most prevalent RNA modification, is involved in all aspects of RNA metabolism, including RNA processing, nuclear export, stability, translation and degradation. Therefore, m6A modification can participate in various physiological functions, such as tissue development, heat shock response, DNA damage response, circadian clock control and even in carcinogenesis through regulating the expression or structure of the gene. The deposition, removal and recognition of m6A are carried out by methyltransferases, demethylases and m6A RNA binding proteins, respectively. Aberrant m6A modification and the dysregulation of m6A regulators play critical roles in the occurrence and development of various cancers. The pathogenesis of esophageal cancer (ESCA) remains unclear and the five-year survival rate of advanced ESCA patients is still dismal. Here, we systematically reviewed the recent studies of m6A modification and m6A regulators in ESCA and comprehensively analyzed the role and possible mechanism of m6A modification and m6A regulators in the occurrence, progression, remedy and prognosis of ESCA. Defining the effect of m6A modification and m6A regulators in ESCA might be helpful for determining the pathogenesis of ESCA and providing some ideas for an early diagnosis, individualized treatment and improved prognosis of ESCA patients.

The Emerging Role of Long Non-Coding RNAs in Esophageal Cancer: Functions in Tumorigenesis and Clinical Implications.

Esophageal cancer (EC) is one of the most common malignancies of digestive tracts with poor five-year survival rate. Hence, it is very significant to further investigate the occurrence and development mechanism of esophageal cancer, find more effective biomarkers and promote early diagnosis and effective treatment. Long non-coding RNAs (lncRNAs) are generally defined as non-protein-coding RNAs with more than 200 nucleotides in length. Existing researches have shown that lncRNAs could act as sponges, guides, scaffolds, and signal molecules to influence the oncogene or tumor suppressor expressions at transcriptional, post-transcriptional, and protein levels in crucial cellular processes. Currently, the dysregulated lncRNAs are reported to involve in the pathogenesis and progression of EC. Importantly, targeting EC-related lncRNAs through genome editing, RNA interference and molecule drugs may be one of the most potential therapeutic methods for the future EC treatment. In this review, we summarized the biological functions and molecular mechanisms of lncRNAs, including oncogenic lncRNAs and tumor suppressor lncRNAs in EC. In addition, we generalized the excellent potential lncRNA candidates for diagnosis, prognosis and therapy in EC. Finally, we discussed the current challenges and opportunities of lncRNAs for EC.

The Influence of Socioeconomic Status on Esophageal Cancer in Taiwan: A Population-Based Study.

Background: Esophageal cancer has extreme worldwide demographic and histologic variations in occurrence; thus, understanding the pathogenesis of esophageal cancer must be region- or country-based. We examined the incidence and tumor stage at diagnosis of esophageal cancer in relation to patients’ socioeconomic status (SES) in Taiwan. Method: This retrospective cohort study used data from Taiwan’s National Health Insurance Research Database and Taiwan Cancer Registry collected between January 2008 and December 2014. The records of 40- to 79-year-old patients diagnosed with esophageal cancer were retrieved. The distribution of the crude incidence rates of esophageal cancer by occupation and income variables was studied retrospectively. Cox proportional hazard model was used to adjust for potential confounders and compare the esophageal cancer incidence among four independent variables: age, gender, occupation, and income. Logistic regression analysis was applied to find the power of the independent variables on the odds ratio of late-stage presentation. Results: The analysis included 7763 subjects. Esophageal squamous cell carcinoma (ESCC) was the predominant histological type (96.6%) and 94.4% of patients were male. The peak affected age for ESCC was 50 to 59 years, whereas the risk of esophageal adenocarcinoma increased progressively with age. The risk of ESCC was significantly unfavorable for the most disadvantaged group, either in occupation or income, while in EAC, risk was unrelated to either factor. The stage of cancer at diagnosis was lower in the highest income groups than in the other two groups. Conclusion: Significant SES disparities in esophageal cancer incidence, based on occupation and income, are present in Taiwan. Low SES populations have a higher percentage of late-stage diagnosis. Resolution of the increasing socioeconomic disparities and narrowing the gaps in health inequities in Taiwan are needed.

Acetyltransferase P300 Inhibits the Proliferation, Invasion, and Migration of Esophageal Cancer via Survivin Acetylation

Background: Esophageal cancer is one of the primary death causes leading by cancer in the world, which is high morbidity and mortality. Epigenetic acetylation modification participates in and regulates the proliferation, invasion, and metastasis of various tumor cells, and the acetylation modification of tumor proteins involved by acetyltransferases may be one of the important mechanisms of esophageal carcinogenesis. The aim of this study was to investigate the correlation of acetyltransferase P300 and Survivin acetylation in esophageal cancer pathogenesis and its molecular mechanism. Methods: Fifty-five cases of esophageal cancer tissues and adjacent cancer tissues were collected, Survivin and P300 protein expression was measured by immunohistochemistry (SP) and protein blotting (Western Blot); Survivin acetylated protein levels were measured by coimmunoprecipitation (Co-IP); bioinformatics predicted the relationship between P300 and Survivin as the substrate, and fluorescence immunohistochemistry (IF) to verify the localization and expression of Survivin and P300 in esophageal cancer tissues; the correlation of Survivin acetylation, P300 and clinical cases characteristics was analyzed by statistics. P300 siRNA sequences were structured and transfected into EC109 cells. P300 protein expression and Survivin acetylated protein levels were determined by Co-IP. Cell viability was determined by the MTT assay, Scratch healing and Transwell chamber assay examined cell migration and invasion ability. Results: Survivin and P300 protein expression was significantly increased in human esophageal cancer tissues and EC109 cells. The Survivin protein was acetylated in esophageal cancer tissues and EC109 cells, and its protein acetylation rate was significantly increased; bioinformatics predicted that the acetyltransferase P300 could catalyze the acetylation of Survivin as a substrate, and the fluorescence immunohistochemistry confirmed that both Survivin and P300 simultaneously showed a high expression state in cancer tissues; Survivin acetylation and P300 expression; Survivin acetylation and P300 were closely related with esophageal cancer stage, tissue differentiation and lymph node metastasis. The vitro experiments showed that P300 RNA interference in esophageal cancer cells can significantly reduce the Survivin protein acetylation level, while inhibiting the survival, migration and invasion capacity of EC109 cells. Conclusion: P300 has a correlation with Survivin acetylation in the lespathological process of esophageal cancer, P300 may be an important upstream molecule of Survivin acetylation and has an important potential value in the diagnosis and treatment of esophageal cancer.

LIMD2 is a Prognostic and Predictive Marker in Patients With Esophageal Cancer Based on a ceRNA Network Analysis.

Globally, esophageal cancer (ECA) is the seventh most common cancer and sixth most common cause of cancer-associated mortality. However, there are no reliable prognostic and predictive molecular markers for ECA; in addition, the pathogenesis of ECA is not fully elucidated. The expressions of circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) of ECA and control groups were obtained from the RNA-sequencing (RNA-seq) data of our hospital, the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) datasets. Analyses of differentially expressed genes, the circRNA–miRNA–mRNA–competing endogenous RNA (ceRNA) network, and functional/pathway enrichment were conducted. The key targets in the ceRNA network that showed significant results in survival Cox regression analyses were selected. Furthermore, analyses of immune infiltration and autophagy genes related to the key targets were performed. Seven circRNAs, 22 miRNAs, and 34 mRNAs were identified as vital genes in ECA; the nuclear factor-κ-gene binding (NF-κB) and phosphatidylinositol-3 kinase/protein kinase B (PI3K-Akt) signaling were identified as the most enriched pathways. In addition, the LIM domain containing 2 (LIMD2) was an independent predictor of prognosis in ECA patients and closely associated with immunity and autophagy. Moreover, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed significant upregulation of LIMD2 expression in ECA tissues. ECA may be closely correlated with NF-κB and PI3K/Akt signaling. In addition, LIMD2 could be a potential prognostic and predictive marker of ECA.

Long non-coding RNA HAGLROS regulates the proliferation, migration, and apoptosis of esophageal cancer cells via the HAGLROS-miR-206-NOTCH3 axis.

Esophageal cancer (EC) is a common malignant tumor of the digestive tract, the treatment of which involves surgery combined with radiotherapy and chemotherapy, as well as other comprehensive types of treatment. The pathogenesis of EC remains unclear, which hinders the development of clinical therapy and the identification of molecular targets for this disease. Long non-coding RNAs (lncRNAs) have been shown to be associated with the malignant biological behavior of EC, but the specific molecular mechanisms underlying the carcinogenesis of EC are not fully understood. Reverse transcription-quantitative PCR (RT-qPCR) was applied to measure the lncRNA HAGLR opposite strand lncRNA (HAGLROS) levels in EC cell lines and tissues. Cell Counting Kit-8 (CCK-8) detection, scratch test, and Transwell assay were performed to determine the proliferation, migration and invasion of EC cell. The interaction between HAGLROS, microRNA (miR)-206, and notch receptor 3 (NOTCH3) was confirmed by RNA immunoprecipitation and dual luciferase reporter gene assays. HAGLROS is upregulated in esophageal squamous cell carcinoma (ESCC) tissues and predicts poor prognosis. Silent HAGLROS is negatively associated with malignant behavior in EC cells. Low expression of HAGLROS can induce decreased invasive and migratory abilities in EC cells. Downregulated HAGLROS significantly inhibits the proliferation of EC cells and accelerates apoptosis. HAGLROS promotes EC cell tumorigenesis in vivo. HAGLROS participates in the HAGLROS/miR-206/NOTCH3 regulatory axis in EC cells. HAGLROS may play a role in the progression of EC by modulating the miR-206/NOTCH3 signaling axis, and may be a novel target for the diagnosis and treatment of EC.

Exosomal lncRNA LINC01711 facilitates metastasis of esophageal squamous cell carcinoma via the miR-326/FSCN1 axis.

Esophageal cancer is a malignant tumor with a five-year survival rate of less than 20%. Early diagnosis and exploration of esophageal cancer pathogenesis are of great significance for the treatment and prognosis of esophageal cancer. Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of different types of tumors. However, the role of exosome LncRNA in esophageal squamous cell carcinoma (ESCC) is rarely reported. In this study, we detected high expression of lncRNA LINC01711 in ESCC tissues and was associated with poor prognosis. Silencing LINC01711 can inhibit the proliferation, migration, invasion, and growth of ESCC cell lines, and induce apoptosis. Linc01711 was identified as a competitive endogenous RNA that suppressed miR-326, and up-regulated the expression of fascin actin-bundling protein 1 (FSCN1). Besides, in vivo experiments showed that the administration of exosome-derived LINC01711 (LINC01711-Exo) promoted the growth of tumors in nude mice. In general, exosomal LINC01711 promoted the proliferation, migration, and invasion of esophageal cancer cells by up-regulating FSCN1 and down-regulating miR-326, thus improved the occurrence and development of ESCC.

METTL3-mediated m6A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway

Esophageal cancer is a lethal malignancy with a high mortality rate, while the molecular mechanisms underlying esophageal cancer pathogenesis are still poorly understood. Here, we found that the N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and associated with poor patient prognosis. Depletion of METTL3 results in decreased ESCC growth and progression in vitro and in vivo. We further established ESCC initiation and progression models using Mettl3 conditional knockout mouse and revealed that METTL3-mediated m6A modification promotes ESCC initiation and progression in vivo. Moreover, using METTL3 overexpression ESCC cell model and Mettl3 conditional knockin mouse model, we demonstrated the critical function of METTL3 in promoting ESCC tumorigenesis in vitro and in vivo. Mechanistically, METTL3-catalyzed m6A modification promotes NOTCH1 expression and the activation of the Notch signaling pathway. Forced activation of Notch signaling pathway successfully rescues the growth, migration, and invasion capacities of METTL3-depleted ESCC cells. Our data uncovered important mechanistical insights underlying ESCC tumorigenesis and provided molecular basis for the development of novel strategies for ESCC diagnosis and treatment.

Psychosocial risk factors associated with esophageal cancer in Chinese cohort: A systematic review and meta-analysis.

Previous studies were controversial about the role of psychosocial factors in the pathogenesis of esophageal cancer (EC). This study aimed to systematically evaluate the effect size of psychosocial risk factors for EC in Chinese cohort.A literature search was conducted in both English and Chinese databases, and odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled using a random-effects model.28 studies were identified with a total of 6951 EC cases and 7469 controls. The meta-analysis indicated a higher risk of EC among the individuals with psychological trauma (OR: 2.36, 95% CI: 1.71–3.26), Type A behavior (OR: 1.40, 95% CI: 1.17–1.67), depression (OR: 4.00, 95% CI: 2.44–6.55), melancholy (OR: 2.06, 95% CI: 1.32–3.20), always in sulks (OR: 2.49, 95% CI: 1.21–5.12), and irritable personality (OR: 2.13, 95% CI: 1.58–2.89). A lower EC risk was found in the individuals with good interpersonal relationship (OR: 0.35, 95% CI: 0.17–0.70) and outgoing personality (OR: 0.39, 95% CI: 0.19–0.78).This meta-analysis suggested a potential association between psychosocial factors and EC risk. For the individuals with psychosocial risk factors, physicians should pay more attention to EC screening.

MiR-493 by regulating of c-Jun targets Wnt5a/PD-L1-inducing esophageal cancer cell development.

BackgroundEsophageal cancer is one of the most common cancers across the globe; the 5‐year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development.MethodsThrough experiments in vivo and in vitro, we explored potential signaling pathways, miR‐493/Wnt5A/c‐JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens.ResultsOverexpression of miR‐493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR‐493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR‐493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR‐493 inhibits the activity of c‐JUN and p‐PI3K/p‐AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c‐JUN binds the promoter region of miR‐493 and suppressed the expression of miR‐493, forming a negative feedback loop.ConclusionsThe miR‐493/Wnt5A/c‐JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.