a Cancer Biology and Genetics Laboratory , Centre of Excellence for Advanced Sciences, National Research Centre , Dokki , Cairo, Egypt.
b Biochemistry Department , National Research Centre , Dokki , Cairo, Egypt.
Nutr Cancer. 2019;71(4):688-700. doi: 10.1080/01635581.2019.1577984. Epub 2019 Mar 12.
The modulatory role of the Bifidobacterium longum (BL), isolated from women breast milk, on some oncogenic and tumor suppressor miRNAs as well as IL-1β and IL6 targeted-miRNAs was investigated using murine colorectal cancer (CRC) induced on the top of inflammatory ulcerative colitis model. The investigation of the oncomiRs miR-21a and miR-155, which regulate IL-6 and IL-1β expression, indicated that both was depressed by BL-administration in healthy and in CRC-mice. BL-administration induced the tumor suppressor miRNAs (miR-145 and miR-15a) expression in both of the healthy and in CRC-mice. The miR-146a expression, which regulates both of IL-1β and IL-6 expression, was decreased after the BL-administration in both of the healthy and in CRC-mice. In CRC-mice, NF-Kb concentration was elevated, however this NF-Kb induction was diminished after the treatment with BL. BL highly enhanced the IL-1β and IL-6 mRNA and protein concentrations in healthy mice. The administration of BL to CRC-mice resulted in a dramatic increase in IL-1β mRNA and IL-1β concentration, which in contrast was accompanied with a decrease in the IL-6 mRNA and IL-6 concentration. BL-administration resulted in a drop in the aberrant crypt foci number in CRC-mice and increased necrosis and fibrosis of the colon cells. The modulatory influence of B. longum on microRNAs may provide an important therapeutic impact in CRC through inhibition of the proliferation, invasion, apoptosis, and cell cycle of tumor cells.
从女性母乳中分离出的长双歧杆菌（BL）对一些致癌和肿瘤抑制 miRNA 以及靶向 IL-1β 和 IL6 的 miRNA 的调节作用进行了研究，方法是在溃疡性结肠炎炎症性溃疡模型的基础上诱导小鼠结直肠癌（CRC）。研究了调节 IL-6 和 IL-1β 表达的致癌 miRNA miR-21a 和 miR-155，结果表明 BL 给药可抑制健康和 CRC 小鼠中的两者表达。BL 给药诱导健康和 CRC 小鼠中的肿瘤抑制 miRNA（miR-145 和 miR-15a）表达。调节两者 IL-1β 和 IL-6 表达的 miR-146a 的表达在健康和 CRC 小鼠中经 BL 给药后降低。在 CRC 小鼠中，NF-Kb 浓度升高，但经 BL 处理后，这种 NF-Kb 诱导作用减弱。BL 显著增强了健康小鼠中 IL-1β 和 IL-6 的 mRNA 和蛋白浓度。BL 给药可使 CRC 小鼠中 IL-1β mRNA 和 IL-1β 浓度急剧增加，而 IL-6 mRNA 和 IL-6 浓度则降低。BL 给药可使 CRC 小鼠中异常隐窝灶数量减少，并增加结肠细胞的坏死和纤维化。B. longum 对 microRNAs 的调节作用可能通过抑制肿瘤细胞的增殖、侵袭、凋亡和细胞周期，对 CRC 产生重要的治疗作用。
