CASC2 inhibits the growth, migration, and invasion of thyroid cancer cells through sponging miR-18a-5p/FIH1 axis

Kaohsiung J Med Sci. 2021 Apr;37(4):268-275. doi: 10.1002/kjm2.12331. Epub 2020 Dec 17.

Abstract

Long noncoding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) has been proved to contribute to the development of cancers. However, the mechanism behind the action of CASC2 in thyroid cancer is not quite clear. We demonstrated that CASC2 was downregulated in thyroid cancer. We noted that CASC2 overexpression restrained the growth, migration, and invasion of thyroid cancer cells, whereas CASC2 depletion caused opposite trends. Bioinformatics analysis predicted that hypoxia inducible factor 1 subunit alpha inhibitor (FIH-1) was potentially targeted by miR-18a-5p, which was confirmed by luciferase reporter assay. Upregulation of FIH-1 abrogated the promotive effect of miR-18a-5p on the growth and invasion of thyroid cancer cells. In addition, CASC2 serves as a competing endogenous RNA (ceRNA) and a ''sponge'' for miR-18a-5p, thereby regulating the expression of FIH-1. These data elucidated the CASC2/miR-18a-5p ceRNA network in thyroid cancer pathogenesis.

Keywords: CASC2; invasion; proliferation; thyroid cancer.

MeSH terms

  • Base Pairing
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • MIRN18A microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • long non-coding RNA CASC2, human
  • Mixed Function Oxygenases
  • Luciferases
  • HIF1AN protein, human