Circ_MBNL3 Restrains Hepatocellular Carcinoma Progression by Sponging miR-873-5p to Release PHF2

Biochem Genet. 2023 Jun;61(3):1015-1034. doi: 10.1007/s10528-022-10295-4. Epub 2022 Nov 15.

Abstract

Background Circular RNAs (circRNAs) have shown key regulatory roles in human malignancies. The working mechanism of circRNAs in hepatocellular carcinoma (HCC) remains to be elucidated. Methods Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-20-deoxyuridine (EdU) assay, and colony formation assay. Xenograft tumor model was established to analyze the role of circ_MBNL3 on tumor growth in vivo. Results Circ_MBNL3 expression was notably down-regulated in HCC tissues and cell lines. Circ_MBNL3 overexpression suppressed the proliferation, migration, and invasion and induced the apoptosis of HCC cells. miR-873-5p directly targeted the 3' untranslated region (3'UTR) of PHF2, and PHF2 was negatively regulated by miR-873-5p in HCC cells. miR-873-5p silencing-induced anti-tumor influences were largely reversed by the interference of PHF2 in HCC cells. Circ_MBNL3 restrained xenograft tumor growth in vivo. Conclusion Circ_MBNL3 restrained the proliferation, migration, and invasion and promoted the apoptosis of HCC cells depending on the regulation of miR-873-5p/PHF2 axis.

Keywords: Hepatocellular carcinoma; PHF2; circ_MBNL3; miR-873-5p.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Carcinoma, Hepatocellular* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Homeodomain Proteins
  • Humans
  • Liver Neoplasms* / genetics
  • MicroRNAs* / genetics
  • RNA, Circular / genetics
  • RNA-Binding Proteins / genetics

Substances

  • RNA, Circular
  • 3' Untranslated Regions
  • MicroRNAs
  • PHF2 protein, human
  • Homeodomain Proteins
  • MBNL3 protein, human
  • RNA-Binding Proteins
  • MIRN873 microRNA, human