hsa_circ_0002980 prevents proliferation, migration, invasion, and epithelial-mesenchymal transition of liver cancer cells through microRNA-1303/cell adhesion molecule 2 axis

Aging (Albany NY). 2023 Dec 19;15(24):14915-14929. doi: 10.18632/aging.205317. Epub 2023 Dec 19.

Abstract

Background: Liver cancer (LC) is a rare malignancy. Circular RNA (circRNA) dysregulation is associated with LC metastasis. hsa_circ_0002980 was found to be unexpectedly downregulated in LC tissues; however, its specific function remains unclear.

Methods: hsa_circ_0002980 expression was confirmed using RT-qPCR. The effects of circ_0002980 on the proliferation, metastasis, and EMT-related proteins of LC cells were assessed using clone formation, flow cytometry, Transwell assays, and Western blotting. The relationship between circ_0002980 and miR-1303 or miR-1303 and CADM2 was analyzed using a dual-luciferase reporter assay. Thereafter, the influence of these three genes on LC cell progression was determined through rescue experiments.

Results: hsa_circ_0002980 expression was lower in LC. circ_0002980 overexpression inhibited the proliferation, migration, invasion, and EMT of LC cells. In addition, circ_0002980 specifically binds to miR-1303, and the accelerated effect of miR-1303 overexpression on LC progression was partially reversed by circ_0002980. Moreover, miR-1303 can also target CADM2, and CADM2-mediated prevention can also be attenuated by miR-1303 overexpression.

Conclusions: In LC cells, circ_0002980 upregulation prevents cell proliferation, metastasis, and EMT by affecting the miR-1303/CADM2 axis. Therefore, this axis may be a novel therapeutic target in LC.

Keywords: cell adhesion molecule (CADM) 2; hsa_circ_0002980; liver cancer; microRNA-1303.

MeSH terms

  • Cell Adhesion Molecules / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • MicroRNAs* / genetics
  • RNA, Circular* / genetics

Substances

  • Cell Adhesion Molecules
  • MicroRNAs
  • MIRN1303 microRNA, human
  • RNA, Circular