MFI2-AS1 regulates the aggressive phenotypes in glioma by modulating MMP14 via a positive feedback loop

Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5884-5895. doi: 10.26355/eurrev_201907_18333.

Abstract

Objective: Long noncoding RNAs (lncRNAs) have vital functions during the progression of malignant tumors. Nevertheless, the precise function of lncRNA MFI2 Antisense RNA 1 (MFI2-AS1) in glioma remains not well elaborated.

Patients and methods: The quantitative Real Time PCR (qPCR) assay was used to assess the level of MFI2-AS1, matrix metalloproteinase 14 (MMP14), and miR-485-5p in glioma tissues and cell lines. The growth of glioma cell was analyzed using the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The migration and invasion of glioma cell were investigated using wound healing and transwell invasion analysis. The apoptosis of glioma cell was detected using flow cytometry. The expression of MMP14 was determined by Western blotting. The growth of glioma cell in vivo was assessed using the xenograft model.

Results: We showed that MFI2-AS1 was markedly overexpressed in glioma cells and clinical tissues. The higher level of MFI2-AS1 is related to the poor prognosis in patients with glioma. Furthermore, the downregulation of MFI2-AS1 suppresses the growth, aggressiveness, and induces apoptosis of glioma cells. Also, MMP14 is the target gene of miR-485-5p and its level is positively modulated by MFI2-AS1. The rescue experiments reveal that miR-485-5p inhibition reverses the suppressive impacts of MFI2-AS1 silencing on the growth, migration, and invasive abilities of glioma cells. Finally, we elaborate that MFI2-AS1 silencing represses glioma cell growth in vivo and suppress the expression of MMP14.

Conclusions: In summary, the downregulation of MFI2-AS1 restrains the aggressive phenotypes of glioma cells via downregulating the expression of MMP14.

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Male
  • Matrix Metalloproteinase 14 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Phenotype
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • RNA, Long Noncoding
  • MMP14 protein, human
  • Matrix Metalloproteinase 14