Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis

Mol Med Rep. 2021 May;23(5):375. doi: 10.3892/mmr.2021.12014. Epub 2021 Mar 24.

Abstract

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis because of its insensitivity to radiation and chemotherapy. Recently, circular RNAs (circRNAs) have been found to serve important roles in hepatocellular carcinogenesis. circ‑CCT3, a novel circRNA, was screened from the differential tissue expression results of a circRNA microarray. Relative expression levels of circ‑CCT3 in specimens and cell lines were evaluated by reverse transcription‑quantitative PCR and the relationship between circ‑CCT3 and prognosis was analyzed by Kaplan‑Meier curves. The oncogenic role of circ‑CCT3 was confirmed in HCC cells through a cell counting kit‑8 (CCK‑8) assay, a colony formation assay, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, a wound‑healing assay and a Transwell assay. Bioinformatics prediction and luciferase reporter assays validated that circ‑CCT3 facilitated HCC progression through the miR‑1287‑5p/TEA domain transcription factor 1 (TEAD1) axis. TEAD1 could then directly activate patched 1 and lysyl oxidase transcription, as analyzed by chromatin immunoprecipitation and luciferase reporter assays. The present study identified a novel circRNA, circ‑CCT3, which may be used as a potential therapeutic target for HCC.

Keywords: hepatocellular carcinoma; circ‑CCT3; miR‑1287‑5p; TEA domain transcription factor 1.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Patched-1 Receptor / genetics*
  • Protein-Lysine 6-Oxidase / genetics
  • RNA, Circular / genetics*
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • MIRN1287 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • PTCH1 protein, human
  • Patched-1 Receptor
  • RNA, Circular
  • TEAD1 protein, human
  • Transcription Factors
  • LOX protein, human
  • Protein-Lysine 6-Oxidase

Grant support

The present study was supported by the Research Foundation of Qiqihar Academy of Medical Sciences (grant no. QMSI2019M-27).