CircXPO1 Promotes Glioblastoma Malignancy by Sponging miR-7-5p

Cells. 2023 Mar 8;12(6):831. doi: 10.3390/cells12060831.

Abstract

Mounting evidence suggests that circular RNAs play important roles in the development and progression of cancers. However, their function in glioblastomas (GBM) is still unclear. By circRNA array analysis, we found that circXPO1 (hsa_circ_102737) was significantly upregulated in GBM, and qPCR analysis verified that the circXPO1 expression level was increased in both GBM tissues and cell lines. Functional studies demonstrated that the knockdown of circXPO1 in GBM cell lines repressed cell proliferation and migration; conversely, the overexpression of circXPO1 promoted the malignancy of GBM cells. In line with these findings, circXPO1 inhibition effectively suppressed gliomagenesis in the in situ transplantation model of nude mice. Through bioinformatic analyses and dual-luciferase reporter assays, we showed that circXPO1 directly bound to miR-7-5p, which acted as a tumor suppressor through the negative regulation of RAF1. In conclusion, our studies suggest that the circXPO1/miR-7-5p/RAF1 axis promotes brain tumor formation and may be a potential therapeutic target for GBM treatment.

Keywords: RAF1; ceRNA; circXPO1; glioblastomas; miR-7-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms* / metabolism
  • Glioblastoma* / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • RNA, Circular / metabolism

Substances

  • MicroRNAs
  • RNA, Circular

Grants and funding

This work was supported by the Ministry of Science and Technology China Brain Initiative Grant (2022ZD0204701), and by grants from the National Natural Sciences Foundation of China (32170969), High-level students returning to China (team) project in Hangzhou (2017), Zhejiang Provincial Natural Science Foundation of China (LY19C090002), and Scientific Research Fund of Zhejiang Provincial Education Department (Y202147674).