circHIPK3 regulates cell proliferation and migration by sponging microRNA-124 and regulating serine/threonine kinase 3 expression in esophageal squamous cell carcinoma

Bioengineered. 2022 Apr;13(4):9767-9780. doi: 10.1080/21655979.2022.2060776.

Abstract

Circular RNAs (circRNAs) are a type of important non-coding RNAs that widely involve in the physiological and pathophysiological process. Recent research has established a link between circHIPK3 and the malignant activity of cancer cells. However, circHIPK3' role in esophageal squamous cell carcinoma (ESCC) still needs more focus. To determine the prognostic value of circHIPK3 in patients with ESCC, the expression of circHIPK3 was quantified in 32 pairs of ESCC using real-time polymerase chain reaction (RT-qPCR). Then, the correlation between circHIPK3 expression and clinical characteristics of patients was also analyzed. The function of circHIPK3 in the development of ESCC was investigated using cell biology studies and bioinformatics. The results showed that the expression of circHIPK3 was considerably higher in tumor tissues from ESCC patients than that of adjacent tissues, which was associated with a poor prognosis. Additionally, silencing of circHIPK3 expression retarded esophageal cancer cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro, as well as the growth in vivo. Mechanistically, we discovered that circHIPK3 behaved like a sponge, absorbing microRNA-124 (miR-124) and promoting serine/threonine kinase 3 (AKT3) expression. Our findings indicate that circHIPK3 acts as an oncogene in ESCC and that the circHIPK3-AKT3 axis may be a therapeutic target for patients with ESCC.

Keywords: AKT3; EMT; ESCC; circHIPK3; miR-124; proliferation.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics*
  • Serine / metabolism
  • Serine-Threonine Kinase 3

Substances

  • MIRN124 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Serine
  • Serine-Threonine Kinase 3

Grants and funding

The project was supported by the Cancer Hospital, Chinese Academy of Medical Sciences, Shenzhen Center/Shenzhen Cancer Hospital Research Project [grant no. SZ2020QN003] and the Shenzhen Key Medical Discipline Construction Fund [grant no. SZXK075] and the Sanming Project of Medicine in Shenzhen [grant no. SZSM201612097].