Upregulation of long noncoding RNA FERRE promoted growth and invasion of breast cancer through modulating miR-19a-5p/EZH2 axis

Eur Rev Med Pharmacol Sci. 2020 Nov;24(21):11154-11164. doi: 10.26355/eurrev_202011_23603.

Abstract

Objective: It has been demonstrated that long non-coding RNA (LncRNA) plays an important regulatory role in a series of diseases. The purpose of this study is to investigate the expression of long non-coding RNA (LncRNA) FERRE and its facilitating effects on proliferation and invasion of breast cancer by regulating oncogene EZH2 through sponging with miR-19a-5p.

Patients and methods: qRT-PCR was performed to detect the expressions of FERRE and EZH2 in human breast cancer tissues and cells. CCK-8 assay was performed to evaluate the MCF-7 cells proliferation and transwell assay was performed to evaluate the MCF-7 cells migration. Correlation analysis between FERRE and miR-19a-5p was detected by statistical analysis. Bioinformatics prediction was made to detect the binding site of FERRE and miR-19a-5p and Luciferase activity was conducted to investigate the interaction between EZH2 and miR-19a-5p. Furthermore, we cloned the mice EZH2 3'-UTR into the Luciferase reporter vector and constructed miR-19a-5p binding mutants to validate the inhibited modulation of miR-19a-5p to the EZH2 expression.

Results: Results showed that expression of FERRE and EZH2 were upregulated in human breast cancer tissues and cells. qRT-PCR and CCK-8 assay showed that FERRE expression is associated with the proliferation of breast cancer cells, upregulated FERRE contributed to cell proliferation of MCF-7. Transwell assay showed that FERRE was associated with the migration ability of tumor cells, increased expression of FERRE promoted the migration and invasion of breast cancer cells. The bioinformatics prediction and Luciferase assay demonstrated that by sponging with miR-19a-5p, FERRE can serve as a molecular sponge to further regulate the expression of EZH2.

Conclusions: We found that lncRNA-FERRE was upregulated in human breast cancer patients, which could accelerate tumor proliferation, migration and invasion as a molecular sponge by modulating the inhibitory effect of miR-19a-5p on oncogene EZH2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • Humans
  • MCF-7 Cells
  • Male
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tumor Cells, Cultured
  • Up-Regulation*

Substances

  • MIRN19 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein