Journal Article

miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression

Chandi Charan Mandal, Triparna Ghosh-Choudhury, Nirmalya Dey, Goutam Ghosh Choudhury and Nandini Ghosh-Choudhury

in Carcinogenesis

Volume 33, issue 10, pages 1897-1908
Published in print October 2012 | ISSN: 0143-3334
Published online June 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs198
miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression

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Increasing evidence shows 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′-untranslated region (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 was 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 that blocks miR-21, thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer.

Journal Article.  8549 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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