hsa_circRNA6448-14 promotes carcinogenesis in esophageal squamous cell carcinoma

• Published in: Aging (Albany, NY.) NY.), 2020-08, Vol.12 (15), p.15581-15602
• Main Authors: Zhang, Yaowen, Yuan, Xiang, Yue, Ning, Wang, Lidong, Liu, Junqi, Dai, Ningtao, Yang, Haijun, Fan, Ruitai, Zhou, Fuyou
• Format: Article
• Language: English
• Subjects: Aged; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Cell Differentiation; Cell Line, Tumor; Disease-Free Survival; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - metabolism; Esophageal Squamous Cell Carcinoma - pathology; Esophageal Squamous Cell Carcinoma - therapy; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; Research Paper; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/AGING.103650

Circular RNAs (circRNAs) play important roles in cancer progression. hsa_circRNA6448-14 originates from exon 5 to exon 11 of the TGFBI gene. We investigated the roles of hsa_circRNA6448-14 in esophageal squamous cell carcinoma (ESCC) with microarrays and quantitative real-time polymerase chain reaction (qRT-PCR), Kaplan-Meier analysis, loss-of-function and gain-of-function assays, and pull-down assays for miRNA binding. The hsa_circRNA6448-14-miRNA-mRNA network was drawn using Circos. hsa_circRNA6448-14 was significantly upregulated in ESCC tissues and cell lines. As a diagnostic biomarker, hsa_circRNA6448-14 had an area under the curve (AUC), sensitivity, and specificity of 0.906, 82.9%, and 85.5%, respectively. hsa_circRNA6448-14 upregulation was correlated with poor differentiation, advanced pTNM stage, poor disease-free survival (DFS), and poor overall survival (OS). Elevated hsa_circRNA6448-14 promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro. hsa_circRNA6448-14 functioned as a miRNA sponge to competitively bind miR-455-3p, and hsa_circRNA6448-14 expression negatively correlated with that of miR-455-3p. hsa_circRNA6448-14 promoted carcinogenesis in ESCC, suggesting that hsa_circRNA6448-14 could serve as a diagnostic and prognostic biomarker for ESCC.