CircNDC80 promotes glioblastoma multiforme tumorigenesis via the miR-139-5p/ECE1 pathway

J Transl Med. 2023 Jan 12;21(1):22. doi: 10.1186/s12967-022-03852-3.

Abstract

Background: Circular RNAs (circRNAs) have been shown to be essential for the emergence and growth of different cancers. However, further research is required to validate the function of circRNA in glioblastoma (GBM).

Methods: CircNDC80 expression in both normal brain tissues (NBTs) and glioma tissues was determined using real-time PCR. The impact of circNDC80 on GBM cell proliferation, migration, and invasion was then confirmed by CCK-8, colony formation, EdU incorporation, Transwell, and wound healing assays. To determine how circNDC80 affects the capacity of glioma stem cells (GSCs) to maintain their stemness and self-renewal, a CellTiter-Glo assay, clonogenic assay and extreme limiting dilution assay were utilized. To ascertain the impact of circNDC80 in vivo, intracranial xenograft models were established.

Results: When compared to NBT, glioblastoma tissue had a higher level of circNDC80 expression. In functional assays, circNDC80 promoted glioblastoma cell proliferation, migration, and invasion, while sustaining the stemness and fostering the self-renewal of glioma stem cells. In addition, a dual luciferase reporter assay and circRIP were used to verify that circNDC80 simultaneously affects the expression of ECE1 mRNA by sponging miR-139-5p, and a rescue experiment was used to verify the above results further.

Conclusions: According to our research, circNDC80 is an oncogenic factor that promotes glioblastoma through the miR-139-5p/ECE1 pathway. This implies that circNDC80 may be employed as a novel therapeutic target and a possible predictive biomarker.

Keywords: CircNDC80; ECE1; GSCs; Glioblastoma; miR-139-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • Endothelin-Converting Enzymes
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Glioma*
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism

Substances

  • ECE1 protein, human
  • Endothelin-Converting Enzymes
  • MicroRNAs
  • MIRN139 microRNA, human
  • RNA, Circular
  • NDC80 protein, human