近年來已有文獻(xiàn)指出適當(dāng)?shù)臓I養(yǎng)補(bǔ)充可有效幫助癌癥患者，其中又以魚油最受到注目,。魚油中內(nèi)含許多ω3多元不飽和脂肪酸，包括docosahexaenoic acid (DHA) （十二碳六烯酸）,。
越來越多的證據(jù)表明魚油對體外細(xì)胞水平和動物模型中乳腺癌的生長和侵襲有抑制作用,。乳腺癌細(xì)胞所表達(dá)的CSF-1（細(xì)胞集落刺激因子1）是惡性腫瘤轉(zhuǎn)移強(qiáng)有力的激活因子,。近日Carcinogenesis雜志刊登的一則研究報(bào)告中，研究人員用兩個(gè)人源乳腺癌細(xì)胞株MDA-MB-231和MCF-7證實(shí),，魚油的生物活性成分DHA（十二碳六烯酸）能抑制這些癌細(xì)胞CSF-1的表達(dá),，同時(shí)也能抑制其分泌。
研究人員發(fā)現(xiàn)腫瘤抑制蛋白PTEN通過PI3激酶/Akt信號通路的轉(zhuǎn)錄機(jī)制調(diào)節(jié)CSF-1的表達(dá),。有趣的是,，DHA能顯著抑制miR-21的表達(dá)。此外,，miR-21-誘導(dǎo)CSF-1基因mRNA表達(dá)水平上調(diào),，其轉(zhuǎn)錄水平的上調(diào)能被和miR-21識別序列以及缺乏3'UTR的PTEN基因所阻止。
引人注目的是,，miR-21能逆轉(zhuǎn)DHA減少CSF-1表達(dá)和分泌的功效,。最后，研究數(shù)據(jù)顯示 miR-21以及CSF-1的表達(dá)在給予補(bǔ)充魚油的飲食小鼠的乳腺腫瘤組織中明顯減弱,。研究結(jié)果揭示了魚油飲食阻斷miR-21,，從而增加PTEN的水平，能防止CSF-1在乳腺癌中的表達(dá)發(fā)揮抗腫瘤作用,。（生物谷：Bioon.com）
doi:10.1093/carcin/bgs198
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miR-21 is Targeted By Omega-3 Polyunsaturated Fatty Acid to Regulate Breast Tumor CSF-1 Expression.
Mandal CC, Ghosh-Choudhury T, Dey N, Ghosh Choudhury G, Ghosh-Choudhury N.
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.
