circZFR regulates thyroid cancer progression by the miR-16/MAPK1 axis

Environ Toxicol. 2021 Nov;36(11):2236-2244. doi: 10.1002/tox.23337. Epub 2021 Jul 28.

Abstract

Previous studies have identified the dysregulation of various circRNAs in many types of human cancers including thyroid cancer (TC). Circular RNA ZFR (circZFR) serves as an oncogenic circRNA in TC. However, the detailed molecular mechanism of circZFR in TC progression remains to be further explored. CircZFR and miR-16 expressions in TC cells were analyzed through qRT-PCR. Cell viability, invasion, and apoptosis were detected using CCK-8, transwell invasion assay, and flow cytometry analysis, respectively. The relationship between circZFR and miR-16 was explored using luciferase reporter assay, RNA pull-down assay, and qRT-PCR. The relationship between miR-16 and mitogen-activated protein kinase 1 (MAPK1) was explored using luciferase reporter assay and western blot analysis. Results showed that circZFR was upregulated and miR-16 was downregulated in TC cells. CircZFR knockdown inhibited the viability and invasion and induced apoptosis in TC cells. CircZFR inhibited miR-16 expression by sponging miR-16 and miR-16 repressed MAPK1 expression by targeting MAPK1. Moreover, circZFR positively regulated MAPK1 expression in TC cells by serving as a ceRNA of miR-16. Mechanistically, circZFR knockdown-induced inhibition of cell viability and invasion and promotion of apoptosis were overturned after miR-16 downregulation and promotion of MAPK1. Collectively, circZFR knockdown retarded TC progression by sponging miR-16 and modulating MAPK1 expression.

Keywords: MAPK1; circZFR; miR-16; thyroid cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • MicroRNAs* / genetics
  • Mitogen-Activated Protein Kinase 1
  • RNA, Circular
  • Thyroid Neoplasms* / genetics

Substances

  • MIRN16 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1