hsa_circRNA6448-14 promotes carcinogenesis in esophageal squamous cell carcinoma

Aging (Albany NY). 2020 Aug 15;12(15):15581-15602. doi: 10.18632/aging.103650. Epub 2020 Aug 15.

Abstract

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.

Keywords: esophageal squamous cell carcinoma; hsa_circRNA6448-14; microRNA sponge; microarray; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • RNA, Circular