MiR-433-3p restrains the proliferation, migration and invasion of glioma cells via targeting SMC4

Brain Res. 2021 Sep 15:1767:147563. doi: 10.1016/j.brainres.2021.147563. Epub 2021 Jun 18.

Abstract

Objective: Glioma is a common primary malignant brain tumor characterized by high mortality and poor prognosis. The purpose of this study is to explore the molecular mechanism underlying glioma, aiming to provide a new target for the treatment of glioma to improve the prognosis of patients.

Methods: The differentially expressed genes and regulatory axis affecting the prognosis of glioma were identified with bioinformatics analysis, and the expression of miR-433-3p and SMC4 mRNA was detected with qRT-PCR. The expression of SMC4 and epithelial-mesenchymal transition (EMT)-associated proteins were detected with western blot. The targeting relationship between miR-433-3p and SMC4 was verified with dual-luciferase reporter gene assay. The proliferative ability of glioma cells was detected with CCK-8 assay, while the migration and invasion of glioma cells were detected with Transwell assay.

Results: We found that the expression of SMC4 was significantly up-regulated in glioma, showing that SMC4 was an unfavorable factor for prognosis and could promote the progression of cancer cells. Its upstream regulator miR-433-3p was significantly down-regulated in glioma, which inhibited the development of cancer cells. Moreover, miR-433-3p could target to inhibit the expression of SMC4. Rescue assay showed that miR-433-3p could affect the development of glioma by regulating the expression of SMC4.

Conclusion: Our data demonstrate for the first time that SMC4 is a direct target of miR-433-3p, and elucidate the molecular mechanism by which miR-433-3p inhibits the malignant progression of glioma by targeting and down-regulating the expression of SMC4.

Keywords: Glioma; Invasion; MiR-433-3p; Migration; Proliferation; SMC4.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Databases, Genetic
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • RNA, Circular / genetics
  • Transcriptome / genetics

Substances

  • Chromosomal Proteins, Non-Histone
  • MIRN433 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Adenosine Triphosphatases
  • SMC4 protein, human