CircKRT14 upregulates E2F3 by interacting with miR-1256 to act as an oncogenic factor in esophageal cancer

Hum Exp Toxicol. 2023 Jan-Dec:42:9603271231155093. doi: 10.1177/09603271231155093.

Abstract

Background: A growing number of studies have focused on the regulatory role of circular RNAs (circRNAs) in a variety of cancers. The purpose of this study was to investigate the effect of circRNA Keratin 14 (circKRT14) on the progression of esophageal cancer (EC).

Methods: The levels of circKRT14, miR-1256 and E2F transcription factor 3 (E2F3) were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot. The circular structure of circKRT14 was confirmed by RNase R digestion assay. Cell apoptosis, migration and invasion were detected by flow cytometry and transwell assay. The protein levels of related factors were determined by western blot. The relationship between miR-1256 and circKRT14 or E2F3 was verified by dual-luciferase reporter assay. The in vivo function of circKRT14 was studied by xenograft tumor assay.

Results: CircKRT14 was significantly increased in EC tissues and cells. CircKRT14 silencing inhibited EC cell proliferation, migration, and invasion, but promoted EC cell apoptosis in vitro. CircKRT1 acted as a sponge for miR-1256 in EC, and in-miR-1256 abolished the inhibitory effect of circKRT14 suppression on EC cell progression. E2F3 was a target of miR-1256 and functioned as an oncogene in EC cells. MiR-1256 curbed EC progression by downregulating E2F3. CircKRT14 could affect E2F3 expression by targeting miR-1256. CircKRT14 regulated EC progression in vivo through miR-1256/E2F3 axis.

Conclusions: These results uncovered that circKRT14 up-regulated the expression of E2F3 and promoted the malignant development of EC through sponging miR-1256.

Keywords: E2F3; Esophageal cancer; circKRT14; miR-1256.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • E2F3 Transcription Factor / genetics
  • E2F3 Transcription Factor / metabolism
  • Esophageal Neoplasms* / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • RNA, Circular / metabolism

Substances

  • E2F3 protein, human
  • E2F3 Transcription Factor
  • MicroRNAs
  • MIRN1256 microRNA, human
  • RNA, Circular