Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

Saxena, Reshu; Klochkova, Alena; Murray, Mary Grace; Kabir, Mohammad Faujul; Samad, Safiyah; Beccari, Tyler; Gang, Julie; Patel, Kishan; Hamilton, Kathryn E.; Whelan, Kelly A.

doi:10.3390/cancers11111697

Cited by 27 publications

(25 citation statements)

References 96 publications

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“…The mechanism of autophagy in tumors has long been proposed as a new therapeutic approach. Several studies have supported an association of distinct expression levels between autophagic genes and EAC, showing that ARG regulation may be associated with EAC occurrence and development [ 25 ]. Therefore, we searched for EAC autophagy genes as molecular markers to help design an autophagy-targeted treatment strategy to improve patient prognosis with esophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

Construction and Evaluation of a Risk Score Model for Autophagy-Related Genes in Esophageal Adenocarcinoma

Yuan

et al. 2021

Med Sci Monit

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Background Several studies have suggested the importance of autophagy during esophageal adenocarcinoma (EAC) development. This study aimed to explore the autophagy-related genes correlated with overall survival in patients with EAC. Material/Methods The RNA-seq expression profiles and clinical data of patients with EAC were screened using The Cancer Genome Atlas (TCGA) database. Screening of autophagy-related genes was conducted using the human autophagy database (HADb). Bioinformatic analysis was conducted and included the following: univariate cox, lasso regression, and multivariate cox regression analysis; building overall survival assessment of the prognosis model; drawing the model of receiver operating characteristic (ROC) curve and determining the area under the curve; and a C-index reliability index assessment model through Kaplan-Meier screening of statistically significant genes in the model. The screening results were verified via Oncomine differential expression analysis. Gene set enrichment analysis (GSEA) was further used to analyze the molecular biological functions and related pathways of the gene model. Results Through cox regression and ROC analysis, the model showed that the risk score could accurately and independently predict the prognosis of EAC. The screening identified 4 genes: DAPK1, BECN1, ATG5, and VAMP7. GSEA showed that the high and low expression levels of the 4 genes were mainly enriched in biological functions, such as cell production and regulation, and metabolic pathways that maintain cell activity. Conclusions Our research found that autophagy was involved in the process of EAC development and that several autophagy-related genes may provide prognostic information and clinical application value for patients with EAC.

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Section: Discussionmentioning

confidence: 99%

Construction and Evaluation of a Risk Score Model for Autophagy-Related Genes in Esophageal Adenocarcinoma

Yuan

et al. 2021

Med Sci Monit

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“…Among them, 90% were identified as esophageal squamous cell carcinoma (ESCC) [ 2 ]. The incidence of ESCC was discovered to be extremely high in China: It accounted for about 50% of EC recorded globally [ 3 , 4 ]. In the last 10 years, advanced strategies have been developed to treat multiple cancers, such as surgical operations, radiotherapy and chemotherapy [ 5 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Circ0120816 acts as an oncogene of esophageal squamous cell carcinoma by inhibiting miR-1305 and releasing TXNRD1

Song

Wang

et al. 2020

Cancer Cell Int

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Background Circular RNAs (circRNAs) have been discovered to participate in the carcinogenesis of multiple cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) progression is yet to be properly understood. This research aimed to investigate and understand the mechanism used by circRNAs to regulate ESCC progression. Methods Bioinformatics analysis was first performed to screen dysregulated circRNAs and differentially expressed genes in ESCC. The ESCC tissue samples and adjacent normal tissue samples utilized in this study were obtained from 36 ESCC patients. All the samples were subjected to qRT-PCR analysis to identify the expression of TXNRD1, circRNAs, and miR-1305. Luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay were later conducted to verify the existing relationship among circ0120816, miR-1305 and TXNRD1. CCK-8, BrdU, cell adhesion, cell cycle, western blot and caspase 3 activity assays were also employed to evaluate the regulation of these three biological molecules in ESCC carcinogenesis. To evaluate the effect of circ0120816 on ESCC tumor growth and metastasis, the xenograft mice model was constructed. Results Experimental investigations revealed that circ0120816 was the highest upregulated circRNA in ESCC tissues and that this non-coding RNA acted as a miR-1305 sponge in enhancing cell viability, cell proliferation, and cell adhesion as well as repressing cell apoptosis in ESCC cell lines. Moreover, miR-1305 was observed to exert a tumor-suppressive effect in ESCC cells by directly targeting and repressing TXNRD1. It was also noticed that TXNRD1 could regulate cyclin, cell adhesion molecule, and apoptosis-related proteins. Furthermore, silencing circ0120816 was found to repress ESCC tumor growth and metastasis in vivo. Conclusions This research confirmed that circ0120816 played an active role in promoting ESCC development by targeting miR-1305 and upregulating oncogene TXNRD1.

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“…Esophageal cancer which was the most common malignant tumor all over the world leaded to 508,585 deaths in 2018 [1]. Esophageal squamous cell carcinoma (ESCC) was one of the histological types with high incidence of esophageal cancer in China [2,3]. Compared to other cancers, ESCC had poor survival time in spite of the improving methods for ESCC in the recent 10 years [4,5].…”

Section: Introductionmentioning

confidence: 99%

Circ0120816 Acts As An Oncogene of Esophageal Squamous Cell Carcinoma via Inhibiting miR-1305 and Releasing TXNRD1

Song

Wang

et al. 2020

Preprint

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Background: The morbidity and mortality of esophageal squamous cell carcinoma (ESCC) remains stubbornly high, in spite of emerging new diagnoses methods. The role of circular RNAs (circRNAs) in ESCC progression is still in need of more exploration. Methods: In this research, we gathered 36 patients’ ESCC tissues to analyze the expression of circ0120816, miR-1305 and TXNRD1. KYSE450 and KYSE510 cells were used to conduct the transfection. Aiming to verify our hypothesis, qRT-PCR, RNase R treatment, nuclear extraction, luciferase reporter assay, RNA immunoprecipitation assay, CCK-8, BrdU, cell adhesion, caspase 3 activity assay were used. Results: Circ0120816, upregulated in ESCC, acted as a sponge for miR-1305. Circ0120816 combined miR-1305 to enhance cell viability, proliferation adhesion and repress cell apoptosis in ESCC cell lines. On the contrary, miR-1305 exerted reversed effect in ESCC cells through decreasing TXNRD1. Conclusions: This research demonstrated that circ0120816 promoted ESCC development by competitive binding miR-1305 which could increase the expression of TXNRD1.

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Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

Cited by 27 publications

References 96 publications

Construction and Evaluation of a Risk Score Model for Autophagy-Related Genes in Esophageal Adenocarcinoma

Construction and Evaluation of a Risk Score Model for Autophagy-Related Genes in Esophageal Adenocarcinoma

Circ0120816 acts as an oncogene of esophageal squamous cell carcinoma by inhibiting miR-1305 and releasing TXNRD1

Circ0120816 Acts As An Oncogene of Esophageal Squamous Cell Carcinoma via Inhibiting miR-1305 and Releasing TXNRD1

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