Nutrition & Cancer, 2016, 68(1):154-164.

Soy Isoflavone Genistein-MediatedDownregulation of miR-155 Contributes to theAnticancer Effects of Genistein

Columba De La Parra, Linette Castillopichardo, Ailed Cruzcollazo, et al

Department of Biochemistry , School of Medicine, University of Puerto Rico Medical Sciences Campus , San Juan , Puerto Rico; et al

We previously reported that dietary genistein inhibits mammary tumor growth and metastasis of the highly metastatic MDA-MB-435 cancer cells in immunocompromised mice. The purpose herein was to characterize the role of the novel oncogenic microRNA (miRNA) miR-155 in the anticancer effects of genistein in metastatic breast cancer. The effect of genistein was determined on breast cancer cell viability, apoptosis, and expression of miR-155 and its targets. At low physiologically relevant concentrations, genistein inhibits cell viability and induces apoptosis in metastatic MDA-MB-435 and Hs578t breast cancer cells, without affecting the viability of nonmetastatic MCF-7 breast cancer cells. In parallel with reduced cell viability, miR-155 is downregulated, whereas proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 are upregulated in MDA-MB-435 and Hs578t cells in response to genistein treatment. However, miR-155 levels remain unchanged in response to genistein in the MCF-7 cells. Ectopic expression of miR-155 in MDA-MB-435 and Hs578t cells decreases the effects of genistein on cell viability and abrogates the effects of genistein on apoptosis and expression of proapoptotic genes. Therefore, genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein in metastatic breast cancer.

美国《营养与癌症》, 2016, 68(1):154-164.

大豆异黄酮金雀异黄素介导的miR-155的下调有助于金雀异黄素的抗癌作用

生物化学系，医学院，波多黎各大学医学科学校园，圣胡安，波多黎各问题;et al

我们以前报告膳食染料木黄酮抑制高度转移性MDA-MB-435癌细胞在免疫缺陷小鼠的乳腺肿瘤生长和转移。本文的目的是表征新型致癌微小RNA（miRNA）miR-155在染料木素在转移性乳腺癌的抗癌作用中的作用。确定染料木黄酮对乳腺癌细胞活力，凋亡和miR-155及其靶标的表达的影响。在低生理相关浓度下，染料木黄酮抑制细胞活力并诱导转移性MDA-MB-435和Hs578t乳腺癌细胞中的凋亡，而不影响非转移性MCF-7乳腺癌细胞的生存力。与减少的细胞活力，miR-155下调，而proapoptotic和anticell增殖miR-155目标FOXO3，PTEN，酪蛋白激酶和p27在MDA-MB-435和Hs578t细胞响应染料木素治疗上调。然而，miR-155水平在MCF-7细胞中对染料木黄酮的响应保持不变。 miR-155在MDA-MB-435和Hs578t细胞中的异位表达减少了染料木素对细胞活力的影响，并且消除了染料木素对细胞凋亡和凋亡基因表达的影响。因此，染料木素介导的miR-155的下调有助于染料木素在转移性乳腺癌中的抗癌作用。