Prognostic values of YTHDF1 regulated negatively by mir-3436 in Glioma

J Cell Mol Med. 2020 Jul;24(13):7538-7549. doi: 10.1111/jcmm.15382. Epub 2020 May 25.

Abstract

M6A methylation is likely to be closely associated with the occurrence and development of tumours. In this study, we demonstrated that the transcription levels of the m6A RNA methylation regulators are closely related to the prognosis of glioma. Univariate Cox analysis was performed on the expression levels of methylation regulators and selected three hub genes in glioma. Next, we systematically compared the expression of these m6A RNA methylation regulators in gliomas with different clinicopathological features. The overall survival (OS) curve of the hub genes was initially established based on TCGA database information. YTHDF1 was selected from the hub genes following survival and prognosis analysis. A nomogram was developed to predict the survival probability. We further performed cell function and in vivo xenograft tumour experiments to further verify its role in tumour progression. Next, based on the miRanda and miRDB databases, we predicted one microRNA, hsa-mir-346, that might regulate and bind to 3'UTR of YTHDF1, which was confirmed by our fluorescent enzyme reporter gene experiment. In summary, m6A RNA methylation regulators play a potential role in the progression of gliomas. YTHDF1 may have an essential function in glioma diagnosis, treatment and prognosis.

Keywords: RNA modification; YTHDF1; glioma; miRNA; prognostic signature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Base Sequence
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Survival Analysis

Substances

  • MIRN346 microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins
  • YTHDF1 protein, human