Influence of GO-Antisense miRNA-21 on the Expression of Selected Cytokines at Glioblastoma Cell Lines

Int J Nanomedicine. 2023 Aug 28:18:4839-4855. doi: 10.2147/IJN.S419957. eCollection 2023.

Abstract

Introduction: Graphene oxide (GO) is a single layer of carbon atoms with unique properties, which are beneficial due to its surface functionalisation by miRNA. miRNAs are a non-coding small form of RNA that suppress the expression of protein-coding genes by translational repression or degradation of messenger RNA. Antisense miRNA-21 is very promising for future investigation in cancer therapy. This study aimed to detect cytokine expression levels after the administration of GO-antisense miRNA-21 into U87, U118, U251 and T98 glioma cell lines.

Methods: U87, U118, U251 and T98 glioma cell line were investigated in term of viability, human cytokine expression level at protein and genes after treatment with GO, GO-antisense miRNA-21 and antisense miRNA-21. The delivery of antisense miRNA-21 into the glioma cell at in vitro investigation were conducted by GO based transfection and electroporation.

Results: The results of the protein microarray and gene expression profile showed that complexes of GO-antisense miRNA-21 modified the metallopeptidase inhibitor 2 (TIMP-2), interleukin-6 (IL-6), interleukin 8 (IL-8), intercellular adhesion molecule 1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) expression level compared to transfection by electroporation of antisense miRNA-21 at investigated glioblastoma cell lines. The TIMP-2 protein and gene expression level was upregulated after antisense miRNA-21 delivery by GO complex into U87, U251 and T98 glioblastoma cell lines comparing to the non-treated control group. The downregulation at protein expression level of ICAM - 1 was observed at U87, U118, U251 and T98 glioma cell lines. Moreover, the IL-8 expression level at mRNA for genes and protein was decreased significantly after delivery the antisense-miRNA-21 by GO compared to electroporation as a transfection method.

Discussion: This work demonstrated that the graphene oxide complexes with antisense miRNA-21 can effectively modulate the cytokine mRNA and protein expression level at U87, U118, U251 and T98 glioma cell lines.

Keywords: cancer; glioblastoma; graphene oxide; miRNA delivery; miRNA-21.

MeSH terms

  • Cell Line
  • Cytokines / genetics
  • Glioblastoma* / genetics
  • Glioblastoma* / therapy
  • Glioma*
  • Humans
  • Interleukin-8 / genetics
  • MicroRNAs* / genetics
  • Tissue Inhibitor of Metalloproteinase-2

Substances

  • Cytokines
  • Interleukin-8
  • graphene oxide
  • Tissue Inhibitor of Metalloproteinase-2
  • MIRN21 microRNA, human
  • MicroRNAs