CircCDK17 knockdown inhibits tumor progression and cell glycolysis by downregulaing YWHAZ expression through sponging miR-1294 in cervical cancer

J Ovarian Res. 2022 Feb 15;15(1):24. doi: 10.1186/s13048-022-00952-y.

Abstract

Background: Cervical cancer (CC) is the fourth aggressive tumor affecting women worldwide. Circular RNA (circRNA) is enrolled in CC process. This study aims to unveil the profiles of circ_101119 (circCDK17) in cell proliferation, migration, invasion, apoptosis and glycolysis in CC.

Methods: The expression levels of circCDK17, microRNA-1294 (miR-1294) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). The protein expression levels of YWHAZ, recombinant glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) were determined by western blot. Cell proliferation, migratory and invasive abilities and apoptosis were illustrated by cell counting kit-8 (CCK-8) assay, transwell assay and flow cytometry analysis, respectively. Cell lactate production, glucose uptake and adenosine 5'-triphosphate (ATP) level were severally elucidated by lactate assay kit, glucose assay kit and ATP detection kit.

Results: CircCDK17 expression and the mRNA and protein expression levels of YWHAZ were dramatically upregulated, while miR-1294 expression was obviously downregulated in CC tissues or cells compared with control groups. CircCDK17 silencing suppressed cell proliferation, migration, invasion and glycolysis, and induced cell apoptosis in CC; however, miR-1294 inhibitor restrained these effects. Additionally, circCDK17 was a sponge of miR-1294 and miR-1294 bound to YWHAZ. Furthermore, circCDK17 knockdown inhibited tumor formation in vivo.

Conclusion: CircCDK17 knockdown repressed cell proliferation, migration, invasion and glycolysis, and promoted cell apoptosis via miR-1294/YWHAZ axis in CC. This finding provides a theoretical basis in studying circRNA-mediated therapy in CC.

Keywords: CC; CircCDK17; MiR-1294; YWHAZ.

MeSH terms

  • 14-3-3 Proteins* / genetics
  • 14-3-3 Proteins* / metabolism
  • Animals
  • Apoptosis / genetics
  • Cell Movement / genetics
  • Cell Nucleus / metabolism
  • Cell Proliferation / genetics
  • Cytoplasm / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Gene Silencing
  • Glycolysis / genetics
  • HeLa Cells
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • Neoplasm Transplantation
  • RNA, Circular* / genetics
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • 14-3-3 Proteins
  • MicroRNAs
  • MIRN1294 microRNA, human
  • RNA, Circular
  • YWHAZ protein, human