Hsa_circ_0043278 functions as competitive endogenous RNA to enhance glioblastoma multiforme progression by sponging miR-638

Aging (Albany NY). 2020 Nov 5;12(21):21114-21128. doi: 10.18632/aging.103603. Epub 2020 Nov 5.

Abstract

Circular RNAs have a critical function in the pathogenesis of many diseases and can function as competing endogenous RNA or miRNA sponges to inhibit miRNA and therefore upregulate the expression of target genes. However, little is known about the role of has_circRNA_0043278 (circ_0043278) in glioblastoma multiforme (GBM) and its potential downstream miRNA targets. This work validated that circ_0043278 is highly expressed in GMB cell lines and tissues, while knockdown circ_0043278 inhibited GBM cell migration, proliferation, and invasion invitro and tumorigenesis invivo. Dual-luciferase reporter assay determined that circ_0043278 directly sponged miR-638 to upregulate the expression of HOXA9, which can activate downstream Wnt/β-catenin signaling in GBM. Moreover, miR-638 inhibition reversed circ_0043278 silencing-induced impairment of malignant tumor behavior. These results showed that circ-0043278/miRNA-638/ Homeobox A9 (HOXA9) axis had a vital function in promoting GBM progression. Our findings may provide potential new targets for the diagnosis and therapy of GBM.

Keywords: Wnt/β-catenin signaling; circ_0043278; glioblastoma multiforme; invasion; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / metabolism*
  • Homeodomain Proteins / metabolism
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • RNA, Circular / metabolism*

Substances

  • Homeodomain Proteins
  • MIRN638 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • homeobox protein HOXA9