MiR-4458 inhibits breast cancer cell growth, migration, and invasiveness by targeting CPSF4

Biochem Cell Biol. 2019 Dec;97(6):722-730. doi: 10.1139/bcb-2019-0008. Epub 2019 Apr 10.


Numerous studies have reported that CPSF4 is over-expressed in a large percentage of human lung cancers, and CPSF4 has been identified as a potential oncogene of human lung tumor. Downregulation of CPSF4 inhibits the proliferation and promotes the apoptosis of lung adenocarcinoma cells. A previous study by our group also found overexpression of CPSF4 in breast cancer (BC), and was closely associated with a poor prognosis for the patient. This study investigates microRNAs (miRNAs) that target CPSF4 to modulate BC cell proliferation. We found that miR-4458 was noticeably reduced in BC tissues and cells. Using a miR-4458 mimic, we found that cell proliferation, migration, and invasiveness were suppressed by miR-4458 overexpression, and were enhanced by reducing the expression of miR-4458. Moreover, the results from bioinformatics analyses suggest a putative target site in the CPSF4 3'-UTR. Furthermore, using luciferase reporter assays and Western blotting, we verified that miR-4458 directly targets the 3'-UTR of CPSF4 and downregulates COX-2 and h-TERT, which are downstream target genes of CPSF4. Additionally, PI3K/AKT and ERK were shown to be inhibited by miR-4458 overexpression in BC cells. Moreover, miR-4458 suppresses BC cell growth in vivo. Consequently, these results suggest that the miR-4458-CPSF4-COX-2-hTERT axis might serve as a potential target for the treatment of BC patients.

Keywords: CPSF4; breast cancer; cancer du sein; croissance; growth; invasion; invasiveness; miR-4458; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Cleavage And Polyadenylation Specificity Factor / biosynthesis*
  • Cleavage And Polyadenylation Specificity Factor / genetics*
  • Computational Biology
  • Female
  • Genetic Therapy*
  • Humans
  • Male
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*


  • Cleavage And Polyadenylation Specificity Factor
  • MIRN-4458 microRNA, human
  • MicroRNAs