miR-21 is Targeted By Omega-3 Polyunsaturated Fatty Acid to Regulate Breast Tumor CSF-1 Expression
Menée sur deux lignées cellulaires de cancer du sein et à l'aide d'un modèle murin, cette étude montre que les acides gras polyinsaturés oméga-3 peuvent, en ciblant les microARNs 21, réguler l'expression du facteur CSF-1, impliqué dans les processus carcinogènes et métastatiques
Increasing evidence show the beneficial effects of fish oil on breast cancer growth and invasion in vitro and in animal models. Expression of CSF-1 (colony stimulating factor-1) by breast cancer cells acts as potent activator of malignancy and metastasis. In this report, we used two human breast cancer cell lines MDA-MB-231 and MCF-7 to show that the bioactive fish oil component DHA (docosahexaenoic acid) inhibits expression of CSF-1 and its secretion from these cancer cells. We found that the tumor suppressor protein PTEN regulates CSF-1 expression through PI 3 kinase/Akt signaling via a transcriptional mechanism. The enhanced abundance of microRNA-21 (miR-21) in breast cancer cells contributes to the growth and metastasis. Interestingly, DHA significantly inhibited expression of miR-21. miR-21 Sponge, which derepresses the miR-21 targets, markedly decreased expression of CSF-1 and its secretion. Furthermore, miR-21-induced upregulation of CSF-1 mRNA and its transcription were prevented by expression of PTEN mRNA lacking 3’ UTR and miR-21 recognition sequence. Strikingly, miR-21 reversed DHA-forced reduction of CSF-1 expression and secretion. Finally, we found that expression of miR-21 as well as CSF-1 were significantly attenuated in breast tumors of mice receiving a diet supplemented with fish oil. Our results reveal a novel mechanism for the therapeutic function of fish oil diet which blocks miR-21; thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer.
http://carcin.oxfordjournals.org/content/early/2012/06/07/carcin.bgs198.abstract