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

Abstract

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.