Abstract
BackgroundCircular 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.MethodsBioinformatics 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.ResultsExperimental 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.ConclusionsThis research confirmed that circ0120816 played an active role in promoting ESCC development by targeting miR-1305 and upregulating oncogene TXNRD1.
Highlights
Circular RNAs have been discovered to participate in the carcinogenesis of multiple cancers
Identification of circ0120816/miR‐1305/Thioredoxin reductase 1 (TXNRD1) axis as the key regulator in esophageal squamous cell carcinoma (ESCC) GSE131969 was downloaded from the GEO DateSets and was used to confirm the key circRNA participating in ESCC progression
(See figure on page.) Fig. 1 The identification of circ0120816/miR-1305/TXNRD1 axis in ESCC. a Microarray analysis revealed the top 5 upregulated circRNAs in circRNA microarray GSE131969. b–f RT-qPCR analysis showed the expression of the top 5 upregulated circRNAs in ESCC clinical samples. g The structure of circ0120816. h A total of 72 upregulated differentially expressed genes (DEGs) were overlapped in datasets of GSE33810 and GSE20347 using Venny 2.1.0 analysis. i TXNRD1 was the key gene involved in cell population proliferation. j Eight miRNAs were identified to be overlapped using TargetScan and circInteractome analyses
Summary
Circular RNAs (circRNAs) have been discovered to participate in the carcinogenesis of multiple cancers. The role of circRNAs in esophageal squamous cell carcinoma (ESCC) progression is yet to be properly understood. 90% were identified as esophageal squamous cell carcinoma (ESCC) [2]. Troubling is that the response of patients with ESCC to surgical operations or chemoradiotherapy had been poor, in part because of inadequate early diagnosis as well as the diffuse and invasive nature of this cancer [14, 15]. This unpalatable trend indicates an urgent need for effective molecular target approaches for ESCC therapy [12, 16]
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