UBDP1 pseudogene and UBD network competitively bind miR‑6072 to promote glioma progression

Int J Oncol. 2024 Mar;64(3):29. doi: 10.3892/ijo.2024.5617. Epub 2024 Jan 26.

Abstract

Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non‑coding RNAs, reverse transcription‑quantitative PCR, fluorescence in situ hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for in vivo studies. In vitro and in vivo studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor‑promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR‑6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR‑6072/UBD network may serve as a potential therapeutic strategy for glioma patients.

Keywords: UBD; UBDP1; glioblastoma; microRNA‑6072; pseudogene.

MeSH terms

  • Animals
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioma* / pathology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pseudogenes / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • UBD protein, human

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant nos. 81902538, 82272715, 82272904 and 81872072), the Shanghai Sailing Program (grant no. 19YF1448200) and the Shanghai Basic Research Program (grant no. 19JC1415000).