Emerging roles of circUBAP2 targeting miR-370-3p in proliferation, apoptosis, and invasion of papillary thyroid cancer cells

Hum Cell. 2021 Nov;34(6):1866-1877. doi: 10.1007/s13577-021-00585-1. Epub 2021 Aug 3.

Abstract

Circular RNAs (circRNAs) have been documented to be aberrantly expressed in many types of malignancies and involved in cancer progression. However, their role in thyroid cancer (TC) remains largely unknown. Our study aimed to explore the role and mechanism of circUBAP2 in TC. The differentially expressed circRNAs in TC tissues were identified using GSE18105 from gene expression omnibus (GEO) database. CircUBAP2 and miR-370-3p expression was analyzed using qRT-PCR. The stability of circUBAP2 was confirmed by actinomycin D and RNase R. The subcellular localization of circUBAP2 was detected using cell fractionation assay. Cell proliferation, apoptosis, and invasion were evaluated using MTT, flow cytometry analysis, and Transwell invasion assay, respectively. The interaction between circUBAP2 and miR-370-3p was predicted using bioinformatics analysis and validated by luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation. CircUBAP2 was upregulated and miR-370-3p was downregulated in TC tissues and cells. CircUBAP2 was highly stable, resistant to RNase R digestion, and predominantly localized in the cytoplasm. CircUBAP2 knockdown inhibited cell proliferation and invasion and triggered apoptosis in TC cells. Bioinformatics analysis showed that circUBAP2 contained putative binding sites of miR-370-3p. CircUBAP2 acted as a sponge to inhibit miR-370-3p expression. Mechanistically, miR-370-3p inhibition abolished the effects of circUBAP2 on proliferation, apoptosis, and invasion in TC cells. Taken together, CircUBAP2 knockdown impeded the proliferation and invasion and induced apoptosis in TC cells via sponging miR-370-3p.

Keywords: Apoptosis; CircUBAP2; Invasion; Proliferation; Thyroid cancer; miR-370-3p.

MeSH terms

  • Apoptosis / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics
  • Gene Expression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness / genetics*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • RNA, Circular / physiology*
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*
  • Up-Regulation / genetics

Substances

  • MIRN370 microRNA, human
  • MicroRNAs
  • RNA, Circular