PGC-1 alpha interacts with microRNA-217 to functionally regulate breast cancer cell proliferation

Abstract

Background: In this study, we explored the functional mechanism of PPARg co-activator 1-alpha (PGC-1α) in regulating miR-217-mediated breast cancer development in vitro.

Methods: Dual-luciferase activity assay was applied to examine the binding of miR-217 on PGC-1α gene. Breast cancer cell lines, MCF-7 and MDA-MB-231 were infected by lentivirus to constitutively downregulate miR-217. Its regulation on PGC-1α expression was investigated by qRT-PCR and western blot. PGC-1α gene was subsequently downregulated by siRNA in miR-217-downregulated breast cancer cells to examine its effect on cancer proliferation and cell-cycle progression. In addition, another downstream target gene of miR-217, DACH1, was further downregulated in breast cancer cells to investigate the functional association of PGC-1α and DACH1 in miR-217-mediated breast cancer regulation.

Results: PGC-1α gene was directly bound by human miR-217. Downregulation of miR-217 in MCF-7 and MDA-MB-231 cells increased PGC-1α production at both mRNA and protein levels. SiRNA-mediated PGC-1α downregulation reversed the inhibition of miR-217-downregulaiton on breast cancer proliferation and cell-cycle progression. Moreover, siRNA-mediated DACH1 downregulation further reversed miR-217-downregulaiton induced inhibition on cancer proliferation and cell-cycle progression in PGC-1α downregulated MCF-7 and MDA-MB-231 cells.

Conclusion: MiR-217 is the upstream regulator of PGC-1α in breast cancer regulation in vitro, possibly independent of DACH1 signaling pathway.

Keywords: Breast cancer; DACH1; Lentivirus; PGC-1 alpha; miR-217; siRNA.